Determinants of parental demand of human papillomavirus vaccination for adolescent daughters in China: Contingent valuation survey.

BACKGROUND: Several types of human papillomavirus (HPV) vaccines have been approved for use in adolescent girls in China. These vaccines are regulated as non-National Immunisation Program vaccines and are optional and generally fully self-paid by vaccinees. OBJECTIVE: To assess parents' demand for HPV vaccination by eliciting their willingness-to-pay for their adolescent daughters to be vaccinated against HPV and to examine the determinants of demand for HPV vaccination in China. METHODS: A contingent valuation survey was conducted across three cities in Shandong Province in eastern China. We selected 11 junior middle schools with different socioeconomic features and randomly selected 6 classes in each school, and questionnaires were distributed to all girls aged 12-16 in the 66 classes for their parents to complete. A payment card approach was used to elicit parental willingness-to-pay for HPV vaccination for their daughters. We also collected a wide array of socioeconomic and psychological variables and interval regressions were applied to examine the determinants of parental willingness-to-pay. RESULTS: A total of 1074 eligible parents who completed valid questions were included in analyses. Over 85% of parents believed HPV vaccines were, in general, necessary and beneficiary. However, only around 10% believed that their daughters would be infected by HPV. About 8% of parents would not accept HPV vaccine even if the vaccine were free mainly due to concerns about the potential side effects and vaccine safety and quality issues, and 27.37% would only accept the vaccine if it were free. The median willingness-to-pay was 300 CNY (42 USD). Several factors were positively correlated with higher willingness-to-pay: income, urban residence (relative to rural residence), mothers (relative to fathers), parents' beliefs about vaccine benefits, whether they should make decisions for their daughters, and whether their daughters would be susceptible to HPV. Though education-level was not significantly correlated with willingness-to-pay in the main regressions, a subgroup analysis revealed interesting dynamics in the relation between education and willingness-to-pay across different income-levels. CONCLUSIONS: There is a large gap between parents' willingness-to-pay and the market price of HPV vaccine for girls in China. Parents generally believed the HPV vaccines were beneficial and necessary but when asked for their daughters, most parents did not believe their daughters would be infected by HPV despite the high prevalence in China. Future focus should be on ensuring the provision of accurate health information about HPV prevalence, vaccine quality, and safety to promote vaccine uptake, and promotional efforts tailored to different income groups might yield better effects. Government involvement in negotiating more widely acceptable and affordable prices or subsidising may be necessary for protecting high-risk population groups.

Current status and needs of in-service training for psychiatric nurses in 24 provinces of China: a cross-sectional survey.

Aim: To investigate the current situation and need for post-competence training for psychiatric nurses in China and provide a reference for the development of training programs for psychiatric nurses. Design: A cross-sectional design. Methods: A cross-sectional study was conducted from August to October 2023 with 435 psychiatric nurses from 34 hospitals in 24 provinces of mainland China. A self-administered questionnaire was used for data collection. Descriptive statistics, non-parametric tests, and chi-square tests were used for data analysis. Results: The training content for psychiatric nurses is extensive, and the training load is large. Psychiatric nurses have high training demands for first aid knowledge, emergency handling ability, and anti-riot skills. Nurses with different years of experience have different training needs. The training needs of psychiatric nurses in specialized and general hospitals also different. Conclusion: The training status of psychiatric nurses is not consistent with the demand. Managers should combine this with psychiatric nurses' own work needs to develop practical and effective training programs.

Evaluating local plant species for effective fall armyworm management strategies in Taiwan.

BACKGROUND: The emergence of Spodoptera frugiperda (fall armyworm; FAW) in the world has raised concerns regarding its impact on crop production, particularly on corn and sorghum. While chemical control and Bt crops have been effective in managing FAW damage, the development of pesticide-resistant and Bt-resistant strains necessitates alternative control methods. The push-pull farming system has gained attention, but direct utilization of African plant species in Taiwan faces challenges due to invasive potential and climatic disparities. Therefore, identifying and evaluating suitable local plant species, such as Napier grass (Pennisetum purpureum), Desmodium species, and signal grass (Brachiaria brizantha), is crucial for implementing effective FAW management strategies in Taiwan. RESULTS: In screening fifty Napier grass germplasms, all demonstrated an antibiotic effect, reducing leaf consumption compared to corn. Notably, thirty-five germplasms exhibited robust antibiotic traits, decreasing FAW consumption and increasing mortality rates. Three Napier grass germplasms also attracted more female moths for oviposition. Further evaluation of selected Napier grass germplasms and signal grass demonstrated efficacy in reducing FAW larval weight and survival duration. Additionally, Desmodium species, particularly D. uncinatum, showed promising toxicity against FAW larvae. CONCLUSION: Our findings support the effectiveness of selected Napier grass germplasms and signal grass as pull plants, and highlight the potential of D. uncinatum as a push plant in FAW management strategies in Taiwan.

Interaction between RNF4 and SART3 is associated with the risk of schizophrenia.

The pathogenesis of schizophrenia (SCZ) is heavily influenced by genetic factors. Ring finger protein 4 (RNF4) and squamous cell carcinoma antigen recognized by T cells 3 (SART3) are thought to be involved in nervous system growth and development via oxidative stress pathways. Moreover, they have previously been linked to SCZ. Yet the role of RNF4 and SART3 in SCZ remains unclear. Here, we investigated how these two genes are involved in SCZ by studying their variants observed in patients. We first observed significantly elevated mRNA levels of RNF4 and SART3 in the peripheral blood in both first-episode (n = 30) and chronic (n = 30) SCZ patients compared to controls (n = 60). Next, we targeted-sequenced three single nucleotide polymorphisms (SNPs) in SART3 and six SNPs in RNF4 for association with SCZ using the genomic DNA extracted from peripheral blood leukocytes from SCZ participants (n = 392) and controls (n = 572). We observed a combination of SNPs that included rs1203860, rs2282765 (both in RNF4), and rs2287550 (in SART3) was associated with increased risk of SCZ, suggesting common pathogenic mechanisms between these two genes. We then conducted experiments in HEK293T cells to better understand the interaction between RNF4 and SART3. We observed that SART3 lowered the expression of RNF4 through ubiquitination and downregulated the expression of nuclear factor E2-related factor 2 (NRF2), a downstream factor of RNF4, implicating the existence of a possible shared regulatory mechanism for RNF4 and SART3. In conclusion, our study provides evidence that the interaction between RNF4 and SART3 contributes to the risk of SCZ. The findings shed light on the underlying molecular mechanisms of SCZ and may lead to the development of new therapies and interventions for this disorder.

Helicobacter pylori infection alters gastric microbiota structure and biological functions in patients with gastric ulcer or duodenal ulcer.

BACKGROUND: Helicobacter pylori (H. pylori) infection is closely associated with gastrointestinal diseases. Our preliminary studies have indicated that H. pylori infection had a significant impact on the mucosal microbiome structure in patients with gastric ulcer (GU) or duodenal ulcer (DU). AIM: To investigate the contributions of H. pylori infection and the mucosal microbiome to the pathogenesis and progression of ulcerative diseases. METHODS: Patients with H. pylori infection and either GU or DU, and healthy individuals without H. pylori infection were included. Gastric or duodenal mucosal samples was obtained and subjected to metagenomic sequencing. The compositions of the microbial communities and their metabolic functions in the mucosal tissues were analyzed. RESULTS: Compared with that in the healthy individuals, the gastric mucosal microbiota in the H. pylori-positive patients with GU was dominated by H. pylori, with significantly reduced biodiversity. The intergroup differential functions, which were enriched in the H. pylori-positive GU patients, were all derived from H. pylori, particularly those concerning transfer RNA queuosine-modification and the synthesis of demethylmenaquinones or menaquinones. A significant enrichment of the uibE gene was detected in the synthesis pathway. There was no significant difference in microbial diversity between the H. pylori-positive DU patients and healthy controls. CONCLUSION: H. pylori infection significantly alters the gastric microbiota structure, diversity, and biological functions, which may be important contributing factors for GU.

GLP-1 receptor agonists' impact on cardio-renal outcomes and mortality in T2D with acute kidney disease.

Previous studies have explored the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in reducing cardiovascular events in type 2 diabetes. Here we show that GLP-1 RAs are associated with lower risks of mortality, major cardiovascular events (MACEs), and major adverse kidney events (MAKEs) in type 2 diabetes patients with acute kidney disease (AKD). Utilizing global data from the TriNetX database (2002/09/01-2022/12/01) and propensity score matching, we compare 7511 GLP-1 RAs users to non-users among 165,860 AKD patients. The most common causes of AKI are sepsis (55.2%) and cardiorenal syndrome (34.2%). After a median follow-up of 2.3 years, GLP-1 RAs users exhibit reduced risks of mortality (adjusted hazard ratio [aHR]: 0.57), MACEs (aHR: 0.88), and MAKEs (aHR: 0.73). External validation in a multicenter dataset of 1245 type 2 diabetes patients with AKD supports the favorable outcomes. These results emphasize the potential of GLP-1 RAs in individualized treatment for this population.

The Quantitative Evaluation of Automatic Segmentation in Lumbar Magnetic Resonance Images.

OBJECTIVE: This study aims to overcome challenges in lumbar spine imaging, particularly lumbar spinal stenosis, by developing an automated segmentation model using advanced techniques. Traditional manual measurement and lesion detection methods are limited by subjectivity and inefficiency. The objective is to create an accurate and automated segmentation model that identifies anatomical structures in lumbar spine magnetic resonance imaging scans. METHODS: Leveraging a dataset of 539 lumbar spinal stenosis patients, the study utilizes the residual U-Net for semantic segmentation in sagittal and axial lumbar spine magnetic resonance images. The model, trained to recognize specific tissue categories, employs a geometry algorithm for anatomical structure quantification. Validation metrics, like Intersection over Union (IOU) and Dice coefficients, validate the residual U-Net's segmentation accuracy. A novel rotation matrix approach is introduced for detecting bulging discs, assessing dural sac compression, and measuring yellow ligament thickness. RESULTS: The residual U-Net achieves high precision in segmenting lumbar spine structures, with mean IOU values ranging from 0.82 to 0.93 across various tissue categories and views. The automated quantification system provides measurements for intervertebral disc dimensions, dural sac diameter, yellow ligament thickness, and disc hydration. Consistency between training and testing datasets assures the robustness of automated measurements. CONCLUSION: Automated lumbar spine segmentation with residual U-Net and deep learning exhibits high precision in identifying anatomical structures, facilitating efficient quantification in lumbar spinal stenosis cases. The introduction of a rotation matrix enhances lesion detection, promising improved diagnostic accuracy, and supporting treatment decisions for lumbar spinal stenosis patients.

[Damage and changes in expression of autophagy related factors LC3 and p62 of condylar cartilage in fluorosis mouse].

PURPOSE: To study the damage and the expression of LC3 and p62 of condylar cartilage in fluorosis mouse. METHODS: Thirty 4-week-old male C57BL/6 mice were randomly divided into control group and the experimental group with 15 animals in each group. The control group received regular drinking water and the experimental group received a fluoride concentration of 75 mg/L drinking water for 8 weeks. The structure of condylar cartilage was observed through modified safranine O-fast green FCF cartilage stain kit. Immunohistochemistry was used to detect the expression of MMP-13, type Ⅱ collagen and LC3 and p62. Two-way analysis of variance test was conducted for analysis of semi-quantitative results of immunohistochemistry using SPSS 22.0 software package. RESULTS: Compared with the control group, the fibrocartilage layer of the experimental group became thinner, the condrocytes were smaller, and the staining became deeper.Immunohistochemistry results showed that the expression of MMP-13 and LC3 increased; the expression of type Ⅱ collagen and p62 decreased in the experimental group. CONCLUSIONS: There was degeneration of the condylar cartilage and autophagy in mice with drinking water containing 75 mg/L fluoride.

Quantum gate control of polar molecules with machine learning.

We propose a scheme for achieving basic quantum gates using ultracold polar molecules in pendular states. The qubits are encoded in the YbF molecules trapped in an electric field with a certain gradient and coupled by the dipole-dipole interaction. The time-dependent control sequences consisting of multiple pulses are considered to interact with the pendular qubits. To achieve high-fidelity quantum gates, we map the control problem for the coupled molecular system into a Markov decision process and deal with it using the techniques of deep reinforcement learning (DRL). By training the agents over multiple episodes, the optimal control pulse sequences for the two-qubit gates of NOT, controlled NOT, and Hadamard are discovered with high fidelities. Moreover, the population dynamics of YbF molecules driven by the discovered gate sequences are analyzed in detail. Furthermore, by combining the optimal gate sequences, we successfully simulate the quantum circuit for entanglement. Our findings could offer new insights into efficiently controlling molecular systems for practical molecule-based quantum computing using DRL.

PBI derivatives/surfactant-based fluorescent ensembles: Sensing of multiple aminoglycoside antibiotics and interaction mechanism studies.

Fluorescent aggregates and ensembles have been widely applied in fabrication of fluorescent sensors due to their capacity of encapsulating fluorophores and modulating their photophysical properties. In the present work, fluorescent ensembles based on anionic surfactant SDS assemblies and perylene derivatives (PBIs) were particularly constructed. Three newly synthesized neutral PBI derivatives with different structures, PO, PC1 and PC2, were used for the purpose to evaluate probe structure influence on constructing fluorescent ensembles. The one with hydrophilic side chains, PO, experienced distinct photophysical modulation effect by SDS assemblies. The ensemble based on PO@SDS assemblies displayed effective fluorescence variation to antibiotic aminoglycosides (AGs). To improve cross-reactivity and discrimination capability of ensembles, a second probe, coumarin, was introduced into PO@SDS assemblies. The resultant ternary sensor, CM-PO@SDS, exhibited good qualitative and quantitative detection capabilities, and achieved differentiation of eight AGs and mixed AG samples both in aqueous solution and actual biological fluid, like human serum. Sensing mechanism studies revealed that hydrogen bonding, electrostatic and hydrophobic interactions are involved in the sensing process. This surfactant-based fluorescent ensemble provides a simple and feasible method for assessing AGs levels. Meanwhile, this work may provide some insights to design reasonable probes for constructing effective single-system based discriminative fluorescent amphiphilic sensors.

Targeting SOX4/PCK2 signaling suppresses neuroendocrine trans-differentiation of castration-resistant prostate cancer.

BACKGROUND: Neuroendocrine prostate cancer (NEPC), a lethal subset of prostate cancer (PCa), is characterized by loss of AR signaling and resistance to AR-targeted therapy. While it is well reported that second-generation AR blockers induce neuroendocrine (NE) trans-differentiation of castration-resistant prostate cancer (CRPC) to promote the occurrence of NEPC, and pluripotent transcription factors might be potential regulators, the underlying molecular mechanisms remain unclear. METHODS: We analyzed the data from public databsets to screen candidate genes and then focused on SOX4, a regulator of NE trans-differentiation. The expression changes of SOX4 and its relationship with tumor progression were validated in clinical tumor tissues. We evaluated malignant characteristics related to NEPC in prostate cancer cell lines with stable overexpression or knockdown of SOX4 in vitro. Tumor xenografts were analyzed after inoculating the relevant cell lines into nude mice. RNA-seq, ATAC-seq, non-targeted metabolomics analysis, as well as molecular and biochemical assays were carried out to determine the mechanism. RESULTS: We screened public datasets and identified that expression of SOX4 was significantly elevated in NEPC. Overexpressing SOX4 in C4-2B cells increased cell proliferation and migration, upregulated the expression of NE marker genes, and inhibited AR expression. Consistently, inhibition of SOX4 expression in DU-145 and PC-3 cells reduced the above malignant phenotypes and repressed the expression of NE marker genes. For the in vivo assay, we found that knockdown of SOX4 inhibited tumor growth of subcutaneous xenografts in castrated nude mice which were concomitantly treated with enzalutamide (ENZ). Mechanically, we identified that one of the key enzymes in gluconeogenesis, PCK2, was a novel target of SOX4. The activation of carbohydrate metabolism reprogramming by SOX4 could promote NE trans-differentiation via the SOX4/PCK2 pathway. CONCLUSIONS: Our findings reveal that SOX4 promotes NE trans-differentiation both in vitro and in vivo via directly enhancing PCK2 activity to activate carbohydrate metabolism reprogramming. The SOX4/PCK2 pathway and its downstream changes might be novel targets for blocking NE trans-differentiation.

Non-intubated bronchoscopic tracheobronchial surgeries with electroencephalogram-monitored intravenous anesthesia: feasibility and outcomes.

Background: Anesthesia remains challenging for bronchoscopic tracheobronchial surgeries (BTS) involving surgical manipulations for central airway obstruction within shared airways. To provide complete airway use through intervention with spontaneous breathing without endotracheal tubes, monitored non-intubated anesthesia has been successfully applied with electroencephalogram-derived monitored total intravenous anesthesia. This study evaluated the feasibility and the outcomes of BTS with monitored non-intubated anesthesia. The factors associated with desaturation and complications were also analyzed. Methods: Data from patients receiving non-intubated BTS performed between October 2019 and August 2022 were retrospectively collected. Intraoperative results and postoperative outcomes were analyzed. Results: Data of 92 patients were collected. Supraglottic airways devices and high-flow nasal oxygen were used in 68 and 24 patients respectively. Surgery was successfully completed in 87 patients (94.6%), whereas three patients required conversion to intubation because of substantial bleeding. In total, 11% of patients experienced desaturation [oxygen saturation (SpO2) <90%] for an average of 9 minutes. Unexpected admission to the intensive care unit (ICU) occurred in 12.2% (5/41) of patients from outpatient department and 7.8% (4/51) of hospitalization settings because of high-grade surgical bleeding. With comparable desaturation incidence, tracheal surgery had significantly longer desaturation times (14.5±6.9 min) than bronchial surgeries (5.8±2.6 min) did. Conclusions: Monitored non-intubated anesthesia with spontaneous breathing is feasible for BTS, with high success rate, few complications, and rapid recovery. High-grade bleeding remains the most unpredictable risk for intraoperative desaturation and postoperative ICU admission, especially in tracheal obstruction cases.

Effect of pharmaceutical promotion and incentives offered by pharmaceutical companies on the prescribing pattern of medical students: a cross-sectional study from a developing nation Pakistan.

Background: Pharmaceutical companies continuously pursue healthcare professionals, starting from the medical college level, which can ultimately lead to irrational prescribing of drugs and antibiotics. Therefore, our main aim was to evaluate the opinions and attitudes of medical students toward pharmaceutical promotion. Methods: This study utilized a cross-sectional online survey that applied the snowball sampling technique. Data were collected from three public and three private sector medical colleges in Punjab, Pakistan using snowball sampling. A modified version of a pre-structured questionnaire was used to collect data between October 2020 and January 2021. Medical students from the third year onward were captivated. The tool was made available on Google Forms and students could access it by clicking the link shared. The effect of promotion on prescribing pattern and future prescribing of antibiotics were measured. Descriptive statistics, chi-square, and t-test were used to analyze the data. Results: A total of 1,301 students filled out the survey, but only 1,227 responses were acceptable. The average age was found to be 23.4 ± 1.59 years. Slightly more than half of the respondents were male participants (57.7%), and a significant proportion (84.1%) reported being aware of pharmaceutical promotion. A smaller number (27.7%) felt that physicians who meet medical representatives more frequently tend to prescribe more antibiotics and 46.3% indicated they would be willing to prescribe antibiotics under the promotional influence. Medical students who were male, in senior college years, attended government institutions, and had lower parental income showed significantly higher perception and attitude scores (p < 0.05) which, in turn, may show their inclination to promotional activities. Many students agreed with the view that pharmaceutical promotion (PP) activities may alter prescribing practices and also believed that they contribute to the increased irrational prescribing of drugs and antibiotics. Conclusion: The study revealed that only a small number of students are willing to engage in promotional activities and accept rewards, which influences their choice toward selection of drugs and antibiotics. This study highlighted the necessity of giving proper educational instructions regarding the promotion of drugs to medical students. This study also focused on the educational prerequisites of the students.

Rare codon recoding for efficient noncanonical amino acid incorporation in mammalian cells.

The ability to genetically encode noncanonical amino acids (ncAAs) has empowered proteins with improved or previously unknown properties. However, existing strategies in mammalian cells rely on the introduction of a blank codon to incorporate ncAAs, which is inefficient and limits their widespread applications. In this study, we developed a rare codon recoding strategy that takes advantage of the relative rarity of the TCG codon to achieve highly selective and efficient ncAA incorporation through systematic engineering and big data-model predictions. We highlight the broad utility of this strategy for the incorporation of dozens of ncAAs into various functional proteins at the wild-type protein expression levels, as well as the synthesis of proteins with up to six-site ncAAs or four distinct ncAAs in mammalian cells for downstream applications.

Changes in temporal lobe activation during a sound stimulation task in patients with sensorineural tinnitus: a multi-channel near-infrared spectroscopy study.

BACKGROUND: The subjective sign of a serious pandemic in human work and life is mathematical neural tinnitus. fNIRS (functional near-infrared spectroscopy) is a new non-invasive brain imaging technology for studying the neurological activity of the human cerebral cortex. It is based on neural coupling effects. This research uses the fNIRS approach to detect differences in the neurological activity of the cerebral skin in the sound stimulation mission in order to better discriminate between the sensational neurological tinnitus. METHODS: In the fNIRS brain imaging method, 14 sensorineural tinnitus sufferers and 14 healthy controls listened to varied noise and quiet for fNIRS data collection. Linear fitting was employed in MATLAB to eliminate slow drifts during preprocessing and event-related design analysis. The false discovery rate (FDR) procedure was applied in IBM SPSS Statistics 26.0 to control the false positive rate in multiple comparison analyses. RESULTS: When the ill group and the healthy control group were stimulated by pink noise, there was a significant difference in blood oxygen concentration (P < 0.05), and the healthy control group exhibited a high activation, according to the fNIRS measurement data. The blood oxygen concentration level in the patient group was dramatically enhanced after one month of acupuncture therapy under the identical stimulation task settings, and it was favorably connected with the levels of THI and TEQ scales. CONCLUSIONS: Using sensorineural tinnitus illness as an example, fNIRS technology has the potential to disclose future pathological study on subjective diseases throughout time. Other clinical disorders involving the temporal lobe and adjacent brain areas may also be examined, in addition to tinnitus-related brain alterations.

Vascular endothelial growth factor is an effective biomarker for vascular dementia, not for Alzheimer's disease: A meta-analysis.

INTRODUCTION: Vascular pathology is known to contribute to dementia and vascular endothelial growth factor (VEGF) is a well-established biomarker associated with vascular alterations. Nonetheless, research findings on VEGF in Alzheimer's disease (AD) and vascular dementia (VaD) are inconsistent across various studies. METHODS: We conducted a meta-analysis to elucidate relationships between VEGF and AD/VaD. RESULTS: Twenty-four studies were included. Pooled data showed that both blood and cerebrospinal fluid (CSF) VEGF levels were higher in VaD patients, whereas no significant difference was found between AD patients and healthy controls. However, the correlation between blood VEGF and AD was found among studies with AD pathology verification. And blood VEGF levels were higher in AD patients than controls in "age difference < 5 years" subgroup and CSF samples for European cohorts. DISCUSSION: This study highlights that VEGF is more effective for the diagnosis of VaD and vascular factors are also an important contributor in AD. Highlights: Vascular endothelial growth factor (VEGF) levels were higher in the vascular dementia group, but not in the overall Alzheimer's disease (AD) group.Correlation between VEGF and AD was found among studies with clear AD pathological verification.Elevated VEGF in the cerebrospinal fluid might be a diagnostic marker for AD in European populations.

Targeting TYK2 for Fighting Diseases: Recent Advance of TYK2 Inhibitors.

TYK2 (tyrosine-protein kinase 2) is a non-receptor protein kinase belonging to the JAK family and is closely associated with various diseases, such as psoriasis, inflammatory bowel disease, systemic lupus erythematosus. TYK2 activates the downstream proteins STAT1-5 by participating in the signal transduction of immune factors such as IL-12, IL-23, and IL-10, resulting in immune expression. The activity of the inhibitor TYK2 can effectively block the transduction of excessive immune signals and treat diseases. TYK2 inhibitors are divided into two types of inhibitors according to the different binding sites. One is a TYK2 inhibitor that binds to JH2 and inhibits its activity through an allosteric mechanism. The representative inhibitor is BMS-986165, developed by Bristol-Myers Squibb. The other class binds to the JH1 adenosine triphosphate (ATP) site and prevents the catalytic activity of the kinase by blocking ATP and downstream phosphorylation. This paper mainly introduces the protein structure, signaling pathway, synthesis, structure-activity relationship and clinical research of TYK2 inhibitors.

An optimized ligation-mediated PCR method for chromosome walking and fusion gene chromosomal breakpoints identification.

Molecular techniques that recover unknown sequences next to a known sequence region have been widely applied in various molecular studies, such as chromosome walking, identification of the insertion site of transposon mutagenesis, fusion gene partner, and chromosomal breakpoints, as well as targeted sequencing library preparation. Although various techniques have been introduced for efficiency enhancement, searching for relevant single molecular event present in a large-sized genome remains challenging. Here, the optimized ligation-mediated polymerase chain reaction (PCR) method was developed and successfully identified chromosomal breakpoints far away from the exon of the new exon junction without the need for nested PCR. In addition to recovering unknown sequences next to a known sequence region, the high efficiency of the method could also improve the performance of targeted  next-generation sequencing (NGS).

Comparative Cardiovascular Risks of Febuxostat and Allopurinol in Patients with Diabetes Mellitus and Chronic Kidney Disease.

BACKGROUND Hyperuricemia, which is common in chronic kidney disease and diabetes mellitus patients, raises health concerns. Febuxostat, a first-line urate-lowering agent, prompts cardiovascular risk questions, especially in high-risk patients. This study compared the effects of febuxostat and allopurinol on cardiovascular risk in diabetes mellitus and chronic kidney disease patients. MATERIAL AND METHODS This retrospective observational cohort study, conducted using Taiwan's National Health Insurance Research Database, focused on patients diagnosed with chronic kidney disease and diabetes between January 2012 and December 2017. The study population was divided into 2 groups: allopurinol users (n=12 901) and febuxostat users (n=2997). We performed 1: 1 propensity score matching, resulting in subgroups of 2997 patients each. The primary outcomes were assessed using a competing risk model, estimating hazard ratios (HR) for long-term outcomes, including the risks of all-cause hospitalization, hospitalization for heart failure, and hospitalization for cardiovascular interventions. RESULTS Febuxostat users, compared to allopurinol users, had higher all-cause hospitalization (HR: 1.33; 95% confidence interval [CI]: 1.25 to 1.42; P<.001), hospitalization for heart failure (HR: 1.62; 95% CI: 1.43 to 1.83; P<.001), and hospitalization for cardiovascular interventions (HR: 1.51; 95% CI: 1.32 to 1.74; P<.001). Moreover, the adverse effects of febuxostat on cardiac health were consistent across most subgroups. CONCLUSIONS Use of febuxostat in patients with diabetes mellitus and chronic kidney disease is associated with higher cardiovascular risks compared to allopurinol. Prudent evaluation is essential when recommending febuxostat for this at-risk group.

Counterion docking: a general approach to reducing energetic disorder in doped polymeric semiconductors.

Molecular doping plays an important role in controlling the carrier concentration of organic semiconductors. However, the introduction of dopant counterions often results in increased energetic disorder and traps due to the molecular packing disruption and Coulomb potential wells. To date, no general strategy has been proposed to reduce the counterion-induced structural and energetic disorder. Here, we demonstrate the critical role of non-covalent interactions (NCIs) between counterions and polymers. Employing a computer-aided approach, we identified the optimal counterions and discovered that NCIs determine their docking positions, which significantly affect the counterion-induced energetic disorder. With the optimal counterions, we successfully reduced the energetic disorder to levels even lower than that of the undoped polymer. As a result, we achieved a high n-doped electrical conductivity of over 200 S cm-1 and an eight-fold increase in the thermoelectric power factor. We found that the NCIs have substantial effects on doping efficiency, polymer backbone planarity, and Coulomb potential landscape. Our work not only provides a general strategy for identifying the most suitable counterions but also deepens our understanding of the counterion effects on doped polymeric semiconductors.