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Prenatal stress exerts long-term impact on neurodevelopment in the offspring, with consequences such as increasing the offspring's risk of depression in adolescence and early adulthood. S-ketamine can produce rapid and robust antidepressant effects, but it is not clear yet whether and how S-ketamine alleviates depression in prenatally stressed offspring. The current study incestigated the preliminary anti-depression mechanism of S-ketamine in prenatally stressed offspring, particularly with regard to neuroplasticity. The pregnant females were given chronic unpredictable mild stress on the 7th-20th day of pregnancy and their male offspring were intraperitoneally injected with a single dose of S-ketamine (10 mg/kg) on postnatal day 42. Our findings showed that S-ketamine treatment counteracted the development of depression-like behaviors in prenatally stressed offspring. At the cellular level, S-ketamine markedly enhanced neuroplasticity in the CA1 hippocampus: Golgi-Cox staining showed that S-ketamine alleviated the reduction of neuronal complexity and dendritic spine density; Transmission electron microscopy indicated that S-ketamine reversed synaptic morphology alterations. At the molecular level, by western blot and RT-PCR we detected that S-ketamine significantly upregulated the expression of BDNF and PSD95 and activated AKT and mTOR in the hippocampus. In conclusion, prenatal stress induced by chronic unpredictable mild stress leads to depressive-like behaviors and hippocampal neuroplasticity impairments in male offspring. S-ketamine can produce antidepressant effects by enhancing hippocampal neuroplasticity via the BDNF/AKT/mTOR signaling pathway., (© 2024. The Author(s).)

Novel coumarin-triphenyliminophosphorane (TPIPP) fluorophores, synthesized via a nonhydrolytic Staudinger reaction, exhibit remarkable redox-responsive optical properties. Upon chemical and electrochemical oxidation, these compounds display a hypsochromic shift in absorption from 430 to 350 nm, accompanied by up to 11-fold fluorescence enhancement under 405 nm excitation. The fluorescence switching occurs at an electrochemical oxidation potential of approximately +2.0 V. This enhanced one-photon excited fluorescence is attributed to an emissive radical effect, stemming from in situ generated radical cations at the polarizable iminophosphorane (P=N) bond. The radical formation was confirmed by trapping experiments using tetracyanoquinodimethane, which produced characteristic absorption of radical anions around 850 nm, and by electron spin resonance studies using 5,5-dimethyl-1-pyrroline N -oxide as a spin trap. Conversely, two-photon excited fluorescence under 800 nm pulsed laser excitation decreases upon oxidation, likely due to reduced two-photon absorption resulting from altered π-conjugation. This work demonstrates that external redox modulation can induce significant changes in absorption profiles and enable switching between enhanced one-photon and diminished two-photon excited fluorescence, highlighting the potential of leveraging the controllable radical character of the P=N bond in designing redox-responsive fluorophores., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Introduction: Minimal important change estimates (MIC) are useful for interpreting results of clinical research with quality of life (QoL) as an endpoint. For the European Organisation for Research and Treatment of Cancer head and neck cancer module, the EORTC QLQ-HN43, no such thresholds are established., Methods: Head and neck cancer patients under active treatment (n = 503) from 15 countries completed the EORTC QLQ-HN43 three times (t1: before treatment, t2: three months after t1, t3: six months after t1). A subgroup completed a Subjective Significance Questionnaire (SSQ), indicating experienced change from the previous time point in four QoL domains. QoL was assumed to deteriorate after t1 and improve again until t3. The MIC was established using the average of mean differences in SSQ groups (MIC mean ) and estimates based on logistic regressions (MIC predict ). Additionally, minimal detectable changes (MDC) were computed using 0.5 standard deviation and standard error of the mean., Results: For swallowing, speech, dry mouth, and global QoL, the MIC for deterioration were 13, 14, 26, and 10 respectively. The MIC for improvement were 8 (swallowing), 6 (dry mouth), and 5 (global QoL); no MIC for speech improvement can be presented because of insufficient correlation between change score and anchor. The MDC estimates for deterioration were 15, 14, 15, and 11. For improvement, the MDC estimates were 13, 14, 14, and 11., Conclusions: Our results underline that no single MIC or MDC can be applied to all EORTC QLQ-HN43 scales, and that the MIC for deterioration seems larger than those for improvement., Competing Interests: Declaration of Competing Interest Authors declare they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Study Objective: Although a prolonged heart rate-corrected QT interval (QTcI) is associated with an increased risk of mortality in the general population, its prognostic value in surgical patients remains unclear. We aimed to examine whether preoperative QTcI prolongation predicts short-term postoperative outcomes in elderly patients undergoing noncardiac surgery., Design: The study was a retrospective analysis using the TriNetX network database., Setting: Operating room., Intervention: Assessment and categorization of preoperative QTcI., Patients: Data of patients aged ≥65 years who underwent non-cardiac surgery between 2010 and 2023 were analyzed., Measurements: Patients were categorized into four groups based on preoperative QTcI: long (500-600 ms), borderline (460-500 ms), high-normal (420-460 ms) and control (370-420 ms) groups. The groups were compared using a propensity score-matched analysis. The primary outcome was the all-cause 90-day mortality risk. The secondary outcomes included 90-day risks of postoperative new-onset atrial fibrillation (Af), ventricular arrhythmias (VAs), emergency visits, hospital readmissions, and pneumonia., Results: In total, data on 519,929 patients were collected in this study. Pairwise comparisons showed that all QTcI prolongation groups demonstrated a heightened incidence of postoperative mortality, arrhythmias, and other complications compared to the control group. Patients with a long QTcI had a 3-fold higher risk of mortality (hazard ratio [HR] = 3.124, p < 0.001), Af (HR = 3.059, p < 0.001), and VAs (HR = 3.617, p < 0.001) than controls. The risks of emergency visits (HR = 1.287, p < 0.001), hospital readmissions (HR = 1.591, p < 0.001), and pneumonia (HR = 1.672, p < 0.001) were also higher in the long QTcI group than in the control group. A dose-dependent response was evident between QTcI and mortality as well as arrhythmia risk., Conclusion: Preoperative QTcI screening effectively risk-stratifies elderly surgical patients, with a QTcI≥500 ms being strongly predictive of short-term postoperative mortality and other complications. Incorporating QTcI assessment into the preoperative evaluation may guide perioperative monitoring and management., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Naja atra , the Chinese cobra, is a major cause of snake envenomation in Asia, causing hundreds of thousands of clinical incidents annually. The current treatment, horse serum-derived antivenom, has unpredictable side effects and presents manufacturing challenges. This study focused on developing new-generation snake venom antidotes by using microbial phage display technology to derive nanobodies from an alpaca immunized with attenuated N. atra venom. Following confirmation of the immune response in the alpaca, we amplified V H H genes from isolated peripheral blood mononuclear cells and constructed a phage display V H H library of 1.0 × 10 7 transformants. After four rounds of biopanning, the enriched phages exhibited increased binding activity to N. atra venom. Four nanobody clones with high binding affinities were selected: aNAH1, aNAH6, aNAH7, and aNAH9. Specificity testing against venom from various snake species, including two Southeast Asian cobra species, revealed nanobodies specific to the genus Naja . An in vivo mouse venom neutralization assay demonstrated that all nanobodies prolonged mouse survival and aNAH6 protected 66.6% of the mice from the lethal dosage. These findings highlight the potential of phage display-derived nanobodies as valuable antidotes for N. atra venom, laying the groundwork for future applications in snakebite treatment.IMPORTANCEChinese cobra venom bites present a formidable medical challenge, and current serum treatments face unresolved issues. Our research applied microbial phage display technology to obtain a new, effective, and cost-efficient treatment approach. Despite interest among scientists in utilizing this technology to screen alpaca antibodies against toxins, the available literature is limited. This study makes a significant contribution by introducing neutralizing antibodies that are specifically tailored to Chinese cobra venom. We provide a comprehensive and unbiased account of the antibody construction process, accompanied by thorough testing of various nanobodies and an assessment of cross-reactivity with diverse snake venoms. These nanobodies represent a promising avenue for targeted antivenom development that bridges microbiology and biotechnology to address critical health needs., Competing Interests: The authors declare no conflict of interest.

Objectives: Sexuality is an important dimension of health-related quality of life (HRQOL) in cancer patients. Studies evidence that most patients report impairments of their sexual health related to their disease or its treatment. The Quality of Life Group of the European Organization for the Research and Treatment of Cancer (EORTC) developed a patient reported outcome measure assessing multidimensional aspects of sexual health. The validation study for this instrument revealed heterogenous results for patients in palliative oncological treatment. The aim of this secondary analyses is to examine differences in patient related sexual health outcomes between palliative patients with good performance status (GPS) and those with poor performance status (PPS)., Methods: In this observational cohort study, self-reported sexual health issue scores were compared between the two groups of patients in palliative oncological treatment with GPS vs PPS status., Results: Patients with GPS experienced significantly more sexual satisfaction than patients with PPS (p = 0.015). They reported significantly more treatment effects on their sexual activity (p = 0.005) and suffer more from decreased libido (p = 0.008). Patients with PPS reported significantly more fatigue (p = 0.03) and regarded preservation of sexual activity of higher importance than did patients with GPS (p = 0.049)., Conclusions: Our study demonstrates the importance of sexuality for patients in palliative oncological treatment, especially for those with limited performance status. Considering the patients´ perspective, sexual health reaches beyond physical functioning. Patients in a palliative phase of disease report high levels of psychosexual problems while sexual performance deteriorates. Sexuality is an important aspect of HRQOL for these patients, needs to be addressed by health care providers and sensitively integrated into palliative care plans., (© 2024. The Author(s).)

Background: The primary screening technique for precancerous lesions and cervical cancer is human papillomavirus (HPV) testing, and HPV self-sampling has been shown to be consistent with clinician sampling in terms of the accuracy of the results and may improve cervical cancer screening rates. The aim of this study was to understand the level of awareness, experience, acceptability, and preference for vaginal HPV self-sampling among women in Jiangsu, Zhejiang, and Shanghai, China, and to analyze the possible influencing factors to determine the feasibility of implementing self-sampling., Methods: Overall, 1793 women were included in the data analysis. A self-administered questionnaire was utilized. In addition to descriptive analysis, univariate and multivariate analyses were used to explore the associations between sociodemographic features, history of cervical cancer screening, and the level of awareness, experience, acceptability, and preference for HPV self-samples., Results: The participants' level of awareness of and experience with HPV self-sampling were moderate. A total of 88.8% of participants rated the acceptability as "high", and self-sampling was preferred by 64.2% of them for cervical cancer screening. People aged 45 to 54 years showed a preference for both clinician sampling(OR = 1.762 (1.116-2.163)) and self-sampling (OR = 1.823 (1.233-2.697)). Those who had graduated from high school or above (OR = 2.305 (1.517-3.503), OR = 2.432 (1.570-3.768), OR = 3.258 (2.024-5.244)) preferred clinician-sampling, and those with a bachelor's degree or above (OR = 1.664 (1.042-2.657)) preferred self-sampling. Middle- and high-income individuals showed no preference for either sampling method (OR < 1)., Conclusions: HPV self-sampling is widely accepted, but awareness, experience and preferences need to be improved. These results may help to adjust public health strategies for the early inclusion of HPV self-sampling as a screening method in national initiatives to prevent cervical cancer., (© 2024. The Author(s).)

Streptococcus pneumoniae is a clinically relevant pathogen notorious for causing pneumonia, meningitis, and otitis media in immunocompromised patients. Currently, antibiotic therapy is the most efficient treatment for fighting pneumococcal infections. However, an arise in antimicrobial resistance in S. pneumoniae has become a serious health issue globally. To resolve the problem, alternative and cost-effective strategies, such as monoclonal antibody-based targeted therapy, are needed for combating bacterial infection. S. pneumoniae alpha-enolase (spEno1), which is thought to be a great target, is a surface protein that binds and converts human plasminogen to plasmin, leading to accelerated bacterial infections. We first purified recombinant spEno1 protein for chicken immunization to generate specific IgY antibodies. We next constructed two single-chain variable fragments (scFv) antibody libraries by phage display technology, containing 7.2 × 10 7 and 4.8 × 10 7 transformants. After bio-panning, ten scFv antibodies were obtained, and their binding activities to spEno1 were evaluated on ELISA, Western blot and IFA. The epitopes of spEno1 were identified by these scFv antibodies, which binding affinities were determined by competitive ELISA. Moreover, inhibition assay displayed that the scFv antibodies effectively inhibit the binding between spEno1 and human plasminogen. Overall, the results suggested that these scFv antibodies have the potential to serve as an immunotherapeutic drug against S. pneumoniae infections., (Copyright © 2023. Published by Elsevier B.V.)

An iodine-mediated cyclization has been developed to 4-aryl- NH -1,2,3-triazoles, with p -toluenesulfonyl hydrazide and sulfamic acid used as nitrogen sources. Sulfamic acid plays a crucial role in this reaction by both acting as a substrate and providing an acidic environment. This reaction offers a metal- and azide-free strategy to access NH -1,2,3-triazoles.

Background: Nectin-4 is a novel biomarker overexpressed in various types of cancer, including breast cancer, in which it has been associated with poor prognosis. Current literature suggests that nectin-4 has a role in cancer progression and may have prognostic and therapeutic implications. The present study aims to produce nectin-4-specific single-chain variable fragment (scFv) antibodies and evaluate their applications in breast cancer cell lines and clinical specimens., Methods: We generated recombinant nectin-4 ectodomain fragments as immunogens to immunize chickens and the chickens' immunoglobulin genes were amplified for construction of anti-nectin-4 scFv libraries using phage display. The binding capacities of the selected clones were evaluated with the recombinant nectin-4 fragments, breast cancer cell lines, and paraffin-embedded tissue sections using various laboratory approaches. The binding affinity and in silico docking profile were also characterized., Results: We have selected two clones (S21 and L4) from the libraries with superior binding capacity. S21 yielded higher signals when used as the primry antibody for western blot analysis and flow cytometry, whereas clone L4 generated cleaner and stronger signals in immunofluorescence and immunohistochemistry staining. In addition, both scFvs could diminish attachment-free cell aggregation of nectin-4-positive breast cancer cells. As results from ELISA indicated that L4 bound more efficiently to fixed nectin-4 ectodomain, molecular docking analysis was further performed and demonstrated that L4 possesses multiple polar contacts with nectin-4 and diversity in interacting residues., Conclusion: Overall, the nectin-4-specific scFvs could recognize nectin-4 expressed by breast cancer cells and have the merit of being further explored for potential diagnostic and therapeutic applications., Competing Interests: B-YT is the chairman of Navi Bio-Therapeutics Inc. Taipei, Taiwan. The company has no role in the study’s experimental design, data collection, or interpretation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Leu, Lee, Lin, Wang, Tsai, Lee, Chen, Yang and Lin.)

Periodic mammography and/or sonography examinations are conducted across numerous hospitals nationalwidely, especially for antedees with a positive mammography screening. Despite the regular practice, clinical efficacy of hospital-based breast cancer surveillance remains unclear. Specifically, the impact of surveillance interval upon survival and prognostic surrogates stratified by menopausal status, as well as malignant transition rate should be deciphered. We retrieved cancer registry to ascertain 841 breast cancers with surveillance history through administration data. Healthy controls underwent breast surveillance and were concurrently free of cancer. More benign diseases rather than cancers were identified from premenopausal women (age ≤50 years) with sonography alone within one year, as well as older women (age >50) with both mammography and sonography one to two years before a cancer or benign diagnosis. Among breast cancers, mammography alone during the antecedent one to two years had a protective effect for diagnosing carcinoma in situ rather than invasive cancer (age-adjusted odds ratio: 0.048, P = 0.016). Three-state time homogeneous Markov model showed that hospital-based breast surveillance within 2 years of disease onset reduced the malignant transition rate by 65.16% (59.79-76.74%). The clinical efficacy of breast cancer surveillance was evidenced., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

This aim of this study was to investigate women's knowledge about HPV along with their experience and acceptability of self-sampling in Jiangsu province, China. A total of 862 women aged 25-63 years old from Jiangsu province who purchased an HPV self-sampling test kit were invited to complete a questionnaire designed by the authors. Participants had high acceptability for HPV self-sampling with a mean score of 4.2 (95% [CI], 4.1-4.22) out of 5 points. 27% of participants preferred clinician-sampling, 33% preferred self-sampling, other 40% expressed no preference. Women with good knowledge about HPV and with a good experience with HPV self-sampling were more acceptable for self-sampling (P < 0.05). The biggest concern about HPV self-sampling of the participants includes 'specimens' spoilage', 'incorrect sampling', 'can't get results in time', and so on. HPV self-sampling can be used to improve cervical cancer screening coverage and participation rates in China.

Background and Aims: Peptic ulcer recurrent bleeding occurs in 20% to 30% of patients after standard endoscopic hemostasis, particularly within 4 days after the procedure. The application of additional tranexamic acid (TXA) to the ulcer may enhance hemostasis. This study investigated the effectiveness of TXA powder application on bleeding ulcers during endoscopic hemostasis., Methods: This study enrolled patients who had peptic ulcer bleeding between March 2022 and February 2023. After undergoing standard endoscopic therapy, the patients were randomly assigned to either the TXA group or the standard group. In the TXA group, an additional 1.25 g of TXA powder was sprayed endoscopically on the ulcer. Both groups then received 3 days of high-dose (8 mg/h) continuous infusion proton pump inhibitor therapy. Second-look endoscopy was conducted on days 3 to 4. The primary end point of early treatment failure was defined as ulcer recurrent bleeding within 4 days or major stigmata of recent hemorrhage on the second-look endoscopy., Results: Sixty patients (30 in each group) with peptic ulcer bleeding and balanced baseline characteristics were randomly assigned to a treatment group. The early treatment failure rate was lower in the TXA group (6.7%) than in the standard group (30%) (P = .042). The freedom from treatment failure periods for 4 and 28 days was significantly longer in the TXA group than in the standard group (P = .023). No adverse events from TXA were recorded., Conclusions: The precise delivery of topical TXA alongside standard endoscopic hemostasis reduced the early treatment failure rate in patients with bleeding peptic ulcers. (Clinical trial registration number: NCT05248321.)., Competing Interests: Disclosure All authors disclosed no financial relationships. This study was supported by the National Science and Technology Council, Taiwan (NSTC 111-2622-B-006-002) and National Cheng Kung University Hospital, Taiwan (NCKUH-11103012)., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Ikigai (meaning or purpose in life) is a concept understood by most older adults in Japan. The term has also garnered international attention, with recent academic attempts to map it to concepts in the Western well-being literature. In addition, efforts to use social and home robots to increase well-being have grown; however, they have mostly focused on hedonic well-being (eg, increasing happiness and decreasing loneliness) rather than eudaimonic well-being (eg, fostering meaning or purpose in life)., Objective: First, we explored how Japanese older adults experience ikigai and relate these to concepts in the Western well-being literature. Second, we investigated how a home robot meant to promote ikigai is perceived by older adults., Methods: We used a mixed methods research design-including 20 interviews with older adults, a survey of 50 older adults, and 10 interviews with family caregivers. For interviews, we asked questions about older adults' sources of ikigai, happiness, and social support, along with their perception of the robot (QT). For surveys, a number of well-being scales were used, including 2 ikigai scales-ikigai-9 and K-1-and 6 Patient-Reported Outcomes Measurement Information System scales, measuring meaning and purpose, positive affect, satisfaction with participation in social roles, satisfaction with participation in discretionary social activities, companionship, and emotional support. Questions related to the perception and desired adoption of the robot and older adults' health status were also included., Results: Our results suggest that health is older adults' most common source of ikigai. Additionally, although self-rated health correlated moderately with ikigai and other well-being measures, reported physical limitation did not. As opposed to social roles (work and family), we found that ikigai is more strongly related to satisfaction with discretionary social activities (leisure, hobbies, and friends) for older adults. Moreover, we found that older adults' sources of ikigai included the eudaimonic aspects of vitality, positive relations with others, contribution, accomplishment, purpose, and personal growth, with the first 3 being most common, and the hedonic aspects of positive affect, life satisfaction, and lack of negative affect, with the first 2 being most common. However, the concept of ikigai was most related to eudaimonic well-being, specifically meaning in life, along the dimension of significance. Finally, we found that Japanese older adults have high expectations of a home robot for well-being, mentioning that it should support them in a multitude of ways before they would likely adopt it. However, we report that those with the highest levels of meaning, and satisfaction with their leisure life and friendships, may be most likely to adopt it., Conclusions: We outline several ways to improve the robot to increase its acceptance, such as improving its voice, adding functional features, and designing it to support multiple aspects of well-being., (©Natasha Randall, Waki Kamino, Swapna Joshi, Wei-Chu Chen, Long-Jing Hsu, Katherine M Tsui, Selma Šabanović. Originally published in JMIR Aging (https://aging.jmir.org), 04.10.2023.)

With the advent of direct-acting antiviral agents (DAA) in the recent few years, hepatitis C virus (HCV) infection has become a curable infectious disease. Successful clearance of HCV could lead to improvement of both hepatic and extrahepatic outcomes, such as complications of cirrhosis, hepatocellular carcinoma, cardiovascular diseases, and incident diabetes. However, challenges persist in reaching the HCV elimination goals of the World Health Organization by 2030. Among these challenges are identifying those already infected or undiagnosed subjects, re-linking to the care of known but untreated HCV-infected subjects, and developing strategies to enhance treatment rates and compliance in specific or high-risk populations. In addition, issues of post-DAA viral clearance, including avoiding or preventing reinfection in high-risk populations and surveillance of hepatocellular carcinoma, are important to consolidate the treatment's short- and long-term efficacies. In the current DAA era, treatment is the most effective prevention strategy not only in its excellent efficacy and safety but also in preventing HCV spread. All of the surveillance or measures should center on DAA treatment in clinical practice.

We reported the photoconduction properties of tungsten disulfide (WS 2 ) nanoflakes obtained by the mechanical exfoliation method. The photocurrent measurements were carried out using a 532 nm laser source with different illumination powers. The results reveal a linear dependence of photocurrent on the excitation power, and the photoresponsivity shows an independent behavior at higher light intensities (400-4000 Wm -2 ). The WS 2 photodetector exhibits superior performance with responsivity in the range of 36-73 AW -1 and a normalized gain in the range of 3.5-7.3 10 -6 cm 2 V -1 at a lower bias voltage of 1 V. The admirable photoresponse at different light intensities suggests that WS 2 nanostructures are of potential as a building block for novel optoelectronic device applications., Competing Interests: The authors declare no conflict of interest.

A tandem reaction for the synthesis of phenanthrenes from arynes and α-(bromomethyl)styrenes is reported. The transformation proceeds via an ene reaction of α-(bromomethyl)styrenes with arynes, followed by a [4 + 2] cycloaddition reaction. The reaction generates 9-benzylphenanthrene derivatives in moderate to excellent yields.

Overexpression of human alpha-enolase (hEno1)has been reported in a wide range of cancers and is tightly associated with poor prognosis, making it a remarkable biomarker and therapeutic target. In this study, polyclonal yolk-immunoglobulin (IgY) antibodies purified from hEno1-immunized chickens showed a noticeable specific humoral response. Phage display technology was used to construct two antibody libraries of IgY gene-derived single-chain variable fragments (scFvs) containing 7.8 × 10 7 and 5.4 × 10 7 transformants, respectively. Phage-based ELISA indicated that specific anti-hEno1 clones were significantly enriched. The nucleotide sequences of scFv-expressing clones were determined and classified into seven groups either in the short linker or the long linker. Moreover, higher mutation rates were revealed in the CDR regions, especially in the CDR3. Three distinguish antigenic epitopes were identified on the hEno1 protein. The binding activities of selected anti-hEno1 scFv on hEno1-positive PE089 lung cancer cells were confirmed using Western blot, flow cytometry, and immunofluorescence assay. In particular, hEnS7 and hEnS8 scFv antibodies significantly suppressed the growth and migration of PE089 cells. Taken together, these chicken-derived anti-hEno1 IgY and scFv antibodies have great potential to develop diagnostic and therapeutic agents for the treatment of lung cancer patients with high expression levels of hEno1 protein., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Melasma is a chronic skin condition that adversely impacts quality of life. Although many therapeutic modalities are available there is no single best treatment for melasma. Oral tranexamic acid has been used for the treatment of this condition but its optimal dose is yet to be established., Objectives: We used network meta-analysis to determine the optimal dose of oral tranexamic acid for the treatment of melasma., Methods: We conducted a comprehensive search of all studies of oral tranexamic acid for the treatment of melasma up to September 2020 using PubMed, EMBASE and the Cochrane Library database. The quality of the studies was evaluated using the Jadad score and the Cochrane's risk of bias assessment tool. Only high quality randomised controlled trials were selected. Some studies lacked standard deviation of changes from baseline and these were estimated using the correlation coefficient obtained from another similar study., Results: A total of 92 studies were identified of which 6 randomized controlled trials comprising 599 patients were included to form 3 pair-wise network comparisons. The mean age of the patients in these studies ranged from 30.3 to 46.5 years and the treatment duration ranged from 8 to 12 weeks. The Jadad scores ranged from 5 to 8. The optimal dose and duration of oral tranexamic acid was estimated to be 750 mg per day for 12 consecutive weeks., Limitations: Some confounding factors might not have been described in the original studies. Although clear rules were followed, the Melasma Area and Severity Index and the modified Melasma Area and Severity Index were scored by independent physicians and hence inter-observer bias could not be excluded., Conclusion: Oral tranexamic acid is a promising drug for the treatment of melasma. This is the first network meta-analysis to determine the optimal dose of this drug and to report the effects of different dosages. The optimal dose is 250 mg three times per day for 12 weeks, but 250 mg twice daily may be an acceptable option in poorly adherent patients. Our findings will allow physicians to balance drug effects and medication adherence. Personalized treatment plans are warranted.

A copper(II)-promoted denitrogenation/oxidation reaction for the preparation of primary α-ketoamides was developed using α-azido ketones as a substrate and TEMPO as an oxidant. α-Azido ketones were denitrogenated in situ to form an imino ketone intermediate, which underwent a radical addition process and radical migration to form α-ketoamides. It is worth noting that the imino ketone intermediate is the key to this reaction.

A transition-metal-free intramolecular redox cyclization reaction for the synthesis of cinnolines has been developed from 2-nitrobenzyl alcohol and benzylamine. Mechanistic investigations disclosed the involvement of a key intramolecular redox reaction, followed by condensation, azo isomerization to hydrazone, cyclization, and aromatization to form the desired products. Notably, the formation of intermediate 2-nitrosobenzaldehyde and ( E )-2-(2-benzylidenehydrazineyl) benzaldehyde plays an important role in this transformation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

China's efforts to encourage energy transition from coal to cleaner methods of space heating have gained great achievement. However, not all progress met expectations; that is, some households still rely on solid fuel. Sociocultural factors provide one plausible explanation. While existing studies have examined and quantified the socioeconomic factors, little attention has been paid to the peer effects that are often critical in the Chinese cultural context. This study first presents household energy consumption patterns using household-level data on the coal-switching program in rural Beijing. It shows that the coal-switching program did not completely eliminate the use of solid fuel for space heating as expected. To explore the underlying determinants, we apply an econometric model of the forces driving energy transition, focusing on peer effects. The results confirm that the coal-switching program significantly reduces the use of solid fuel. Moreover, it reveals that the peer effect, measured by the average village-level solid fuel use rate, matters for households' fuel choices. We also find that the peer effect varies with different income levels and policies. These findings provide new evidence and insights for future policy design.

The outcomes for patients with NASH-related HCC after curative resection have not been clarified. This study compared the overall survival (OS), time-to-tumor recurrence (TTR), and recurrence-free survival (RFS) associated with NASH-related HCC and virus-related HCC after resection. Methods: Patients with HCC who underwent curative resection were retrospectively enrolled. Baseline characteristics, including disease etiologies and clinical and tumor features, were reviewed. The primary outcomes were OS, TTR, and RFS. Results: Two hundred and six patients were enrolled (HBV: n = 121, HCV: n = 54, NASH: n = 31). Of those with virus-related HCC, 84.0% achieved viral suppression. In both the overall and propensity-score-matched cohorts, those with NASH-related HCC experienced recurrence significantly earlier than those with virus-related HCC (median TTR: 1108 days vs. non-reached; p = 0.03). Through multivariate analysis, NASH-related HCC (hazard ratio (HR), 2.27; 95% confidence interval (CI), 1.25-4.12) was independently associated with early recurrence. The unadjusted RFS rate of the NASH-related HCC group was lower than the virus-related HCC group. There was no difference in the OS between the two groups. Conclusions: NASH-related HCC was associated with earlier tumor recurrence following curative resection compared to virus-related HCC. Post-surgical surveillance is crucial for detecting early recurrence in patients with NASH-related HCC.

Enterovirus 71 (EV71) is the major etiological agent contributing to the development of hand-foot-mouth disease (HFMD). There are not any global available vaccines or antibody drugs against EV71 released yet. In this study, we perform the virus immunization in a cost-effective and convenient approach by preparing virus particles from size exclusion and immunization of chicken. Polyclonal yolk-immunoglobulin (IgY) was simply purified from egg yolk and monoclonal single-chain variable fragments (scFv) were selected via phage display technology with two scFv libraries containing 6.0 × 10 6 and 1.3 × 10 7 transformants. Specific clones were enriched after 5 rounds of bio-panning and four identical genes were classified after the sequence analysis. Moreover, the higher mutation rates were revealed in the CDR regions, especially in the CDR3. IgY showed specific binding activities to both EV71-infected and Coxsackievirus 16-infected cell lysates and high infectivity inhibitory activity of EV71. However, while IgY detected a 37 kDa protein, the selected scFv seemingly detected higher size proteins which could be cell protein instead of EV71 proteins. Despite the highly effective chicken antibody generation, the purity of virus particles prepared by size exclusion is the limitation of this study, and further characterization should be carried out rigorously.

China is recognized as the largest energy consumer and is also the country with the largest and fastest-aging population. Ongoing demographic changes may reshape China's household-based energy consumption patterns because of the large gap in consumption behavior between the elderly and the young as well as varying attitudes toward the environment among generations. However, when the impact of China's aging population on energy consumption is projected, the heterogeneous cognitive norms of generations in the process of demographic transition are not well understood. In this study, we assessed the future impact of China's demographic transition on energy consumption using a proposed theoretical framework to distinguish between age and generational effects. Specifically, we used age-period-cohort (APC) detrended analysis to estimate age and generational effects based on China's urban household survey data from 1992 to 2015. The results indicated large differences in energy use propensity across ages and generations. The elderly and younger generations tended to be energy-intensive consumers, resulting in higher energy consumption in this aging society. Our results consequently show that future changes in China's elderly population will result in a substantial increase in energy consumption. By 2050, the changing consumption share of the elderly population will account for ∼17 to 26% of total energy consumption in the residential sector, which is close to 115 million tons of standard coal (Mtce). These findings highlight the need to interlace environmental education policies and demographic transitions to promote energy conservation behavior in children and youth for low-carbon, sustainable development.

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus, which is characterized in renal tubulointerstitial fibrosis (TIF). The current study was designed to investigate the protective effect of Jujuboside A (Ju A) on TIF in type 2 diabetes (T2DM) mice, and explore its underlying anti-fibrosis mechanism. A mouse T2DM model was established using high fat diet (HFD) feeding combined with intraperitoneal injection of streptozotocin (STZ). Then, diabetic mice were treated with Ju A (10, 20 and 40 mg·kg -1 ·d -1 , i.g.) for 12 weeks. Results showed that administration of Ju A not only down-regulated fasting blood glucose (FBG) levels, but also improved hyperlipidemia and renal function in diabetic mice. Moreover, the reduced ECM accumulation was observed in the renal cortex of Ju A treated diabetic mice, while the TIF progression was also attenuated by Ju A through blocking the epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells (RTECs). Further mechanism studies showed that Ju A treatment effectively down-regulated the protein expression and subsequent nuclear translocation of Yin Yang 1 (YY1) in the renal cortex of diabetic mice, and reduced the levels of transforming growth factor-β1 (TGF-β1) in the serum and renal cortex of Ju A treated mice. According to invitro studies, the up-regulated YY1/TGF-β1 signaling pathway was restored by Ju A in high glucose (HG) cultured HK-2 cells. Taken together, these findings demonstrated that Ju A can ameliorate the TIF of DN through down-regulating the YY1/TGF-β1 signaling pathway., (Copyright © 2022 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

A Rh(III)-catalyzed tandem reaction for the synthesis of (quinazolin-2-yl)methanone derivatives has been explored from 2,1-benzisoxazoles and α-azido ketones. The transformation involves Rh(III)-catalyzed denitrogenation of α-azido ketones, aza-[4 + 2] cycloaddition, ring opening, and dehydration aromatization processes. Notably, the aza-[4 + 2] cycloaddition of an imine rhodium complex intermediate with 2,1-benzisoxazoles is the key to this reaction.

Background: The current standard of care for patients with newly diagnosed limited-stage small-cell lung cancer (SCLC) is concurrent chemoradiotherapy (CCRT). The prognosis remains poor due to the aggressiveness and high risk of progression or relapse of SCLC even if an initial response is achieved. Therefore, there is an urgent unmet clinical need in this population. The multicenter, phase 3, randomized, placebo-controlled, double-blind KEYLYNK-013 study evaluates the addition of pembrolizumab to CCRT followed by pembrolizumab with or without olaparib in participants with previously untreated limited-stage SCLC. (ClinicalTrials.gov: NCT04624204)., Methods: Eligible participants aged ≥18 years with newly diagnosed, pathologically confirmed, limited-stage (ie, stage I-III) SCLC will be randomized 1:1:1 to CCRT (ie, etoposide plus carboplatin or cisplatin for 4 cycles and standard thoracic radiotherapy) plus pembrolizumab (Groups A and B) or CCRT plus placebo (Group C). In the absence of disease progression, participants will receive pembrolizumab plus placebo (Group A), pembrolizumab plus olaparib (Group B), or placebo (Group C). Dual primary endpoints are progression-free survival per RECIST version 1.1 by blinded independent central review and overall survival., Results: Enrollment began in December 2020 and is ongoing at approximately 150 sites., Conclusions: KEYLYNK-013 will provide valuable information on the efficacy and safety of pembrolizumab plus CCRT and pembrolizumab with or without olaparib post CCRT in participants with limited-stage SCLC., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To evaluate the subjective and objective resuscitation performance of emergency medical technicians (EMTs) using mechanical cardiopulmonary resuscitation (MCPR) devices., Design and Setting: This was a cross-sectional simulation-based study where participants installed the MCPR device on a training manikin., Participants: We assessed EMT-Intermediates (EMT-Is) and EMT-Paramedics (EMT-Ps) of the Emergency Medical Services (Ambulance) Division of the Taipei City Fire Department., Primary and Secondary Outcome Measures: The primary outcome was the gap between self-perceived (subjective) and actual (objective) no-flow time during resuscitation, which we hypothesised as statistically insignificant. The secondary outcome was the association between resuscitation performance and personal attributes like knowledge, attitude and self-confidence., Results: Among 210 participants between 21 and 45 years old, only six were female. There were 144 EMT-Is and 66 EMT-Ps. During a simulated resuscitation lasting between four and a half and 5 min, EMTs had longer actual no-flow time compared with self-perceived no-flow time (subjective, 38 s; objective, 57.5 s; p value<0.001). This discrepancy could cause a 6.5% drop of the chest compression fraction in a resuscitation period of 5 min. Among the EMT personal factors, self-confidence was negatively associated with objective MCPR deployment performance (adjusted OR (aOR) 0.66, 95% CI 0.45 to 0.97, p=0.033) and objective teamwork performance (aOR 0.57, 95% CI 0.34 to 0.97, p=0.037) for EMT-Ps, whereas knowledge was positively associated with objective MCPR deployment performance (aOR 2.15, 95% CI 1.31 to 3.52, p=0.002) and objective teamwork performance (aOR 1.77, 95% CI 1.02 to 3.08, p=0.043) for EMT-Is. Moreover, regarding the self-evaluation of no-flow time, both self-satisfaction and self-abasement were associated with objectively poor teamwork performance., Conclusions: EMTs' subjective and objective performance was inconsistent during the MCPR simulation. Self-confidence and knowledge were personal factors associated with MCPR deployment and teamwork performance. Both self-satisfaction and self-abasement were detrimental to teamwork during resuscitation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In addition to inducing apoptosis, caspase inhibition contributes to necroptosis and/or autophagy depending on the cell type and cellular context. In macrophages, necroptosis can be induced by co-treatment with Toll-like receptor (TLR) ligands (lipopolysaccharide [LPS] for TLR4 and polyinosinic-polycytidylic acid [poly I:C] for TLR3) and a cell-permeable pan-caspase inhibitor zVAD. Here, we elucidated the signaling pathways and molecular mechanisms of cell death. We showed that LPS/zVAD- and poly I:C/zVAD-induced cell death in bone marrow-derived macrophages (BMDMs) was inhibited by receptor-interacting protein kinase 1 (RIP1) inhibitor necrostatin-1 and autophagy inhibitor 3-methyladenine. Electron microscopic images displayed autophagosome/autolysosomes, and immunoblotting data revealed increased LC3II expression. Although zVAD did not affect LPS- or poly I:C-induced activation of IKK, JNK, and p38, it enhanced IRF3 and STAT1 activation as well as type I interferon (IFN) expression. In addition, zVAD inhibited ERK and Akt phosphorylation induced by LPS and poly I:C. Of note, zVAD-induced enhancement of the IRF3/IFN/STAT1 axis was abolished by necrostatin-1, while zVAD-induced inhibition of ERK and Akt was not. Our data further support the involvement of autocrine IFNs action in reactive oxygen species (ROS)-dependent necroptosis, LPS/zVAD-elicited ROS production was inhibited by necrostatin-1, neutralizing antibody of IFN receptor (IFNR) and JAK inhibitor AZD1480. Accordingly, both cell death and ROS production induced by TLR ligands plus zVAD were abrogated in STAT1 knockout macrophages. We conclude that enhanced TRIF-RIP1-dependent autocrine action of IFNβ, rather than inhibition of ERK or Akt, is involved in TLRs/zVAD-induced autophagic and necroptotic cell death via the JAK/STAT1/ROS pathway.

Objectives: To evaluate the effect at a one-year follow-up after an 18-month randomized controlled trial (RCT) of 90 gm/day low-carbohydrate diet (LCD) in type 2 diabetes., Research Design and Methods: Eighty-five poorly controlled type 2 diabetic patients with an initial HbA1c ≥ 7.5% who have completed an 18-month randomized controlled trial (RCT) on 90 g/day low-carbohydrate diet (LCD) were recruited and followed for one year. A three-day weighted food record, relevant laboratory tests, and medication effect score (MES) were obtained at the end of the previous trial and one year after for a total of 30 months period on specific diet., Results: 71 (83.5%) patients completed the study, 35 were in TDD group and 36 were in LCD group. Although the mean of percentage changes in daily carbohydrate intake was significantly lower for those in TDD group than those in LCD group (30.51 ± 11.06% vs. 55.16 ± 21.79%, p = 0.0455) in the period between 18 months and 30 months, patients in LCD group consumed significantly less amount of daily carbohydrate than patients in TDD group (131.8 ± 53.9 g vs. 195.1 ± 50.2 g, p < 0.001). The serum HbA1 C , two-hour serum glucose, serum alanine aminotransferase (ALT), and MES were also significantly lower for the LCD group patients than those in the TDD group (p = 0.017, p < 0.001, p = 0.017, and p = 0.008 respectively). The mean of percentage changes of HbA1 C , fasting serum glucose, 2 h serum glucose, as well as serum cholesterol, triglyceride, low-density lipoprotein, ALT, creatinine, and urine microalbumin, however, were not significantly different between the two groups (p > 0.05)., Conclusions: The one-year follow-up for patients on 90 g/d LCD showed potential prolonged and better outcome on glycaemic control, liver function and MES than those on TDD for poorly controlled diabetic patients., (© 2022. The Author(s).)

Persistent luminescence is a unique optical process where long-lasting afterglow persists after the cessation of excitation. Nanoscale persistent luminescent materials are getting increased research interest from various fields due to their unique optical property. In recent years, inspiring achievements have been made to produce uniform persistent luminescence nanoparticles (PLNPs) in a controllable manner, unleashing their fascinating potential, surpassing other types of luminescent materials in a wide variety of application such as high-contrast bioimaging and high-resolution X-ray detection. In this review, the evolution of uniform PLNPs, from their bulk phosphor counterparts, to the "top-down" preparation of nanoscale persistent luminescent materials, to the recent "bottom-up" synthesis of uniform PLNPs is first summarized. The respective milestones of uniform PLNPs prepared by templated synthesis, aqueous synthesis, and colloidal synthesis are highlighted. The key optical properties that can be enhanced in uniform PLNPs, including increasing the persistent luminescence intensity, tuning the excitation irradiance, as well as the emission wavelengths are then analyzed. Detailed strategies to enhance each optical property are also discussed in various sections. Finally, future challenges are highlighted with respect to the perspectives on the development of next-generation PLNPs with novel applications., (© 2022 Wiley-VCH GmbH.)

Purpose: The aim of this study was to explore what methods should be used to determine the minimal important difference (MID) and minimal important change (MIC) in scores for the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Module, the EORTC QLQ-HN43., Methods: In an international multi-centre study, patients with head and neck cancer completed the EORTC QLQ-HN43 before the onset of treatment (t1), three months after baseline (t2), and six months after baseline (t3). The methods explored for determining the MID were: (1) group comparisons based on performance status; (2) 0.5 and 0.3 standard deviation and standard error of the mean. The methods examined for the MIC were patients' subjective change ratings and receiver-operating characteristics (ROC) curves, predictive modelling, standard deviation, and standard error of the mean. The EORTC QLQ-HN43 Swallowing scale was used to investigate these methods., Results: From 28 hospitals in 18 countries, 503 patients participated. Correlations with the performance status were |r|< 0.4 in 17 out of 19 scales; hence, performance status was regarded as an unsuitable anchor. The ROC approach yielded an implausible MIC and was also discarded. The remaining approaches worked well and delivered MID values ranging from 10 to 14; the MIC for deterioration ranged from 8 to 16 and the MIC for improvement from - 3 to - 14., Conclusions: For determining MIDs of the remaining scales of the EORTC QLQ-HN43, we will omit comparisons of groups based on the Karnofsky Performance Score. Other external anchors are needed instead. Distribution-based methods worked well and will be applied as a starting strategy for analyses. For the calculation of MICs, subjective change ratings, predictive modelling, and standard-deviation based approaches are suitable methods whereas ROC analyses seem to be inappropriate., (© 2021. The Author(s).)

This study aimed to compare stent graft with balloon tamponade for ruptured dialysis access during percutaneous transluminal angioplasty. Patients over an 8-year period (2010-2018) were identified from a database of 11,609 procedures. The primary endpoint was target lesion primary patency at 12 months. A total of 143 patients who had rupture dialysis access were enrolled, of whom 52 were salvaged by stent grafts and 91 were salvaged by balloon tamponade. The 6-month target lesion primary patency was greater in the stent graft group than in the balloon tamponade group (66.7% vs. 29.5%, P < 0.001). The benefit of stent grafts was sustained for 12 months (52.5% vs. 9.0%, P < 0.001). The stent grafts increased the median time from the index procedure to the next intervention in the ruptured area by 171 days (260 vs. 89 days) at 12 months. There was no significant difference in the access circuit patency rates at 6 months (25.5% vs. 19.8%, P = 0.203) and 12 months (12.0% vs. 5.8%, P = 0.052). The patency results of the stent grafts remained after the multivariable adjustment analysis. Compared to balloon tamponade alone, stent grafts provided superior target lesion primary patency at 6 and 12 months. The access circuit patency rates were similar., (© 2022. The Author(s).)

As the world's largest CO 2 emitter, China's ability to decarbonize its energy system strongly affects the prospect of achieving the 1.5 °C limit in global, average surface-temperature rise. Understanding technically feasible, cost-competitive, and grid-compatible solar photovoltaic (PV) power potentials spatiotemporally is critical for China's future energy pathway. This study develops an integrated model to evaluate the spatiotemporal evolution of the technology-economic-grid PV potentials in China during 2020 to 2060 under the assumption of continued cost degression in line with the trends of the past decade. The model considers the spatialized technical constraints, up-to-date economic parameters, and dynamic hourly interactions with the power grid. In contrast to the PV production of 0.26 PWh in 2020, results suggest that China's technical potential will increase from 99.2 PWh in 2020 to 146.1 PWh in 2060 along with technical advances, and the national average power price could decrease from 4.9 to 0.4 US cents/kWh during the same period. About 78.6% (79.7 PWh) of China's technical potential will realize price parity to coal-fired power in 2021, with price parity achieved nationwide by 2023. The cost advantage of solar PV allows for coupling with storage to generate cost-competitive and grid-compatible electricity. The combined systems potentially could supply 7.2 PWh of grid-compatible electricity in 2060 to meet 43.2% of the country's electricity demand at a price below 2.5 US cents/kWh. The findings highlight a crucial energy transition point, not only for China but for other countries, at which combined solar power and storage systems become a cheaper alternative to coal-fired electricity and a more grid-compatible option., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Importance: Passive surveillance systems are susceptible to the under-reporting of adverse events (AE) and a lack of information pertaining to vaccinated populations. Conventional active surveillance focuses on predefined AEs. Advanced data mining tools could be used to identify unusual clusters of potential AEs after vaccination., Objective: To assess the feasibility of a novel tree-based statistical approach to the identification of AE clustering following the implementation of a varicella vaccination program among one-year-olds., Setting and Participants: This nationwide safety surveillance was based on data from the Taiwan National Health Insurance database and National Immunization Information System for the period 2004 through 2014. The study population was children aged 12-35 months who received the varicella vaccine., Exposure: First-dose varicella vaccine., Outcomes and Measures: All incident ICD-9-CM diagnoses (emergency or inpatient departments) occurring 1-56 days after the varicella vaccination were classified within a hierarchical system of diagnosis categories using Multi-Level Clinical Classifications Software. A self-controlled tree-temporal data mining tool was then used to explore the incidence of AE clustering with a variety of potential risk intervals. The comparison interval consisted of days in the 56-day follow-up period that fell outside the risk interval., Results: Among 1,194,189 varicella vaccinees with no other same-day vaccinations, nine diagnoses with clustering features were categorized into four safety signals: fever on days 1-6 (attributable risk [AR] 38.5 per 100,000, p < 0.001), gastritis and duodenitis on days 1-2 (AR 5.9 per 100,000, p < 0.001), acute upper respiratory infection on days 1-5 (AR 11.0 per 100,000, p = 0.006), and varicella infection on days 1-9 (AR 2.7 per 100,000, p < 0.001). These safety profiles and their corresponding risk intervals have been identified in previous safety surveillance studies., Conclusions: Unexpected clusters of AEs were not detected after the mass administration of childhood varicella vaccines in Taiwan. The tree-temporal statistical method is a feasible approach to the safety surveillance of vaccines in populations of young children., Competing Interests: Declaration of Competing Interest This research was supported by a grant from the Taiwan Ministry of Science and Technology (MOST 105-2314-B-002-055-MY2) and National Taiwan University Health Data Research Center. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KA Chan reported receiving grants from Bayer, Takeda, Amgen, Boehringer Ingelheim, MundiPharma, Merck Sharp and Dohme, and GlaxoSmithKline; serving on an advisory committee for Bayer; and receiving speaking fees from Amgen outside the submitted work. The other authors have no potential conflicts of interest to report., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cadmium is a heavy metal which exists widely in industrial and agricultural production and can induce a variety of diseases in organisms. Therefore, its detection is of great significance in the fields of biology, environment and medicine. Fluorescent probe has been a powerful tool for cadmium detection because of its convenience, sensitivity, and bioimaging capability. In this paper, we reviewed 98 literatures on cadmium fluorescent sensors reported from 2017 to 2021, classified them according to different fluorophores, elaborated the probe design, application characteristics and recognition mode, summarized and prospected the development of cadmium fluorescent and colorimetric probes. We hope to provide some help for researchers to design cadmium fluorescent probes with higher selectivity, sensitivity and practicability., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group developed a questionnaire to assess sexual health in patients with cancer and cancer survivors. This study evaluates the psychometric properties of the questionnaire., Methods: The 22-item EORTC sexual health questionnaire (EORTC QLQ-SH22) was administered with the EORTC QLQ-C30 to 444 patients with cancer. The hypothesised scale structure, reliability and validity were evaluated through standardised psychometric procedures., Results: The cross-cultural field study showed that the majority of patients (94.7%) were able to complete the QLQ-SH22 in less than 20 min; 89% of the study participants did not need any help to fill in the questionnaire. Multi-item multi-trait scaling analysis confirmed the hypothesised scale structure with two multi-item scales (sexual satisfaction, sexual pain) and 11 single items (including five conditional items and four gender-specific items). The internal consistency yielded acceptable Cronbach's alpha coefficients (.90 for the sexual satisfaction scale, .80 for the sexual pain scale). The test-retest correlations (Pearson's r) ranged from .70 to .93 except for the scale communication with professionals (.67) and male body image (.69). The QLQ-SH22 discriminates well between subgroups of patients differing in terms of their performance and treatment status., Conclusion: The study supports the reliability, the content and construct validity of the QLQ-SH22. The newly developed questionnaire is clinically applicable to assess sexual health of patients with cancer at different treatment stages and during survivorship for clinical trials and for clinical practice., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Dysphagia is present in 25-50% of patients with stroke. Therefore, studying the probability of nasogastric tube removal in such patients before discharge from the rehabilitation ward is crucial. In this study, we developed a model to predict the outcome of dysphagia in patients with stroke. A retrospective study was performed from May 2015 to December 2018. We reviewed the medical charts of all patients with a diagnosis of stroke receiving nasogastric tube feeding. Patients were divided into weaned and nonweaned groups to compare baseline characteristics and functional status. The weaned and nonweaned groups comprised 55 and 65 patients, respectively. In the final logistic regression analysis model, the Barthel index at admission, lip closing status, ability to answer simple questions and functional independence before stroke were used to develop a predictive model (Logit = 0.8942 × functional independence before this stroke + 1.1279 × ability to answer simple question + 0.5345 × lip-close status + 0.0546 × Barthel index at admission - 2.2805). The optimal cutoff point based on Youden's index was more than -0.8403 with a sensitivity and specificity of 85.45 and 73.85%, respectively. The positive predicted value was 73.44%. In patients with stroke and dysphagia, a high Barthel index, intact lip closing status, ability to answer simple questions and better functional status before stroke appeared to affect nasogastric tube removal before discharge from the rehabilitation ward. Based on the final regression model, the proposed equation will help physicians and speech pathologists in planning patient care., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

To the best of our knowledge, none of Taiwanese studies on the relationship between physical activity (PA) and sarcopenia by the latest 2019 Asian Working Group for Sarcopenia (AWGS) cutoff points of sarcopenia has been published. We used the Taiwan version of international physical activity questionnaire-short version and the 2019 AWGS diagnostic criteria of sarcopenia to examine the relationship between PA and sarcopenia in older adults. Volunteers in this cross-sectional study were recruited from those attending senior health checkup program held at a regional hospital in Taipei City from May 2019 to Sep 2019. Muscle strength was assessed by grip strength, physical performance was assessed by usual gait speed on a 6-m course, and muscle mass was measured by bioelectrical impedance analysis. Multiple logistic regression was used to analyze the relationship between PA and sarcopenia. Odds ratios and corresponding 95% confidence intervals were calculated. 565 participants were recruited and data from 500 participants were used. The study participants had a mean age of 73.87 years old, with 47% men and 53% women. 138 (27.6%) participants were classified as having sarcopenia, among which 48 (45.3%) in low PA participants and 90 (22.8%) in moderate to high PA participants. Compared with those with low PA, moderate to high PA protected against the risk of sarcopenia with the odds ratio (OR) 0.46 (95% CI 0.27-0.79, p-value = 0.005). A significant protective effect of PA on sarcopenia was found among the older adults after adjusting for sex, institutionalization, age, BMI, albumin, hemoglobin, HDL-C levels, history of cardiovascular disease, education level and alcohol drinking.

Coxsackievirus A16 (CA16) is one of the major causative agents of hand, foot, and mouth disease (HFMD). Children aged <5 years are the most affected by CA16 HFMD globally. Although clinical symptoms of CA16 infections are usually mild, severe complications, such as aseptic meningitis or even death, have been recorded. Currently, no vaccine or antiviral therapy for CA16 infection exists. Single-chain variable fragment (scFv) antibodies significantly inhibit viral infection and could be a potential treatment for controlling the infection. In this study, scFv phage display libraries were constructed from splenocytes of a laying hen immunized with CA16-infected lysate. The pComb3X vector containing the scFv genes was introduced into ER2738 Escherichia coli and rescued by helper phages to express scFv molecules. After screening with five cycles of bio-panning, an effective scFv antibody showing favorable binding activity to proteins in CA16-infected lysate on ELISA plates was selected. Importantly, the selected scFv clone showed a neutralizing capability against the CA16 virus and cross-reacted with viral proteins in EV71-infected lysate. Intriguingly, polyclonal IgY antibody not only showed binding specificity against proteins in CA16-infected lysate but also showed significant neutralization activities. Nevertheless, IgY-binding protein did not cross-react with proteins in EV71-infected lysate. These results suggest that the IgY- and scFv-binding protein antibodies provide protection against CA16 viral infection in in vitro assays and may be potential candidates for treating CA16 infection in vulnerable young children.

Background: Changing environmental factors are likely responsible for the rising prevalence of allergic diseases in children. However, whether environmental exposures induce allergen sensitizations, and which allergen sensitization is related to the development of allergic diseases, is not clear. The study is aimed to investigate the association between environmental exposure, allergen sensitization, and the development of allergic diseases for further preventive intervention., Methods: We conducted the Taiwan Childhood Environment and Allergic diseases Study (TCEAS) in kindergarten children in Taiwan. Skin prick tests for 6 allergens were performed. Information on the development of allergic diseases and environmental exposure was collected using standardized questionnaires. Multiple logistic regressions were used to estimate the association between environmental factors, allergen sensitization, and the development of allergic diseases., Results: A total of 3192 children were recruited. 485 (15.2%) children had atopic dermatitis (AD), 1126 (35.3%) had allergic rhinitis (AR), and 552 (17.3%) had asthma. Children with environmental tobacco smoke exposure and fungi on the house wall had a higher risk of asthma, with ORs (95% CIs) of 1.25 (1.03-1.52) and 1.22 (1.01-1.47), respectively. The mite sensitization rate was found to be the highest. Mite sensitization was associated with significant increases in the risks of AD, AR, and asthma, with ORs (95% CIs) of 2.15 (1.53-3.03), 1.94 (1.46-2.58), and 2.31 (1.63-3.29), respectively. Cockroach sensitization also increased the risk of asthma, with an OR (95% CI) of 2.38 (1.01-5.61). Mite sensitization was associated with carpet in the home and fungi on the house wall, and milk sensitization was associated with breastfeeding duration., Conclusion: Environmental exposures play a role in the development of allergic diseases. Allergen sensitizations were associated with certain environmental exposures. Early environmental interventions are urgently needed to prevent the development of childhood allergic diseases., Competing Interests: The authors declare no competing interests., (© 2020 The Authors.)

Aim: This study explored the effect of a moderate (90 g/d) low-carbohydrate diet (LCD) in type 2 diabetes patients over 18 months., Methods: Ninety-two poorly controlled type 2 diabetes patients aged 20-80 years with HbA1c ≥7.5% (58 mmol/mol) in the previous three months were randomly assigned to a 90 g/d LCD r traditional diabetic diet (TDD). The primary outcomes were glycaemic control status and change in medication effect score (MES). The secondary outcomes were lipid profiles, small, dense low-density lipoprotein (sdLDL), serum creatinine, microalbuminuria and carotid intima-media thickness (IMT)., Results: A total of 85 (92.4%) patients completed 18 months of the trial. At the end of the study, the LCD and TDD group consumed 88.0±29.9 g and 151.1±29.8 g of carbohydrates, respectively (p < 0.05). The 18-month mean change from baseline was statistically significant for the HbA1c (-1.6±0.3 vs. -1.0±0.3%), 2-h glucose (-94.4±20.8 vs. -18.7±25.7 mg/dl), MES (-0.42±0.32 vs. -0.05±0.24), weight (-2.8±1.8 vs. -0.7±0.7 kg), waist circumference (-5.7±2.7 vs. -1.9±1.4 cm), hip circumference (-6.1±1.8 vs. -2.9±1.7 cm) and blood pressure (-8.3±4.6/-5.0±3 vs. 1.6±0.5/2.5±1.6 mmHg) between the LCD and TDD groups (p<0.05). The 18-month mean change from baseline was not significantly different in lipid profiles, sdLDL, serum creatinine, microalbuminuria, alanine aminotransferase (ALT) and carotid IMT between the groups., Conclusions: A moderate (90 g/d) LCD showed better glycaemic control with decreasing MES, lowering blood pressure, decreasing weight, waist and hip circumference without adverse effects on lipid profiles, sdLDL, serum creatinine, microalbuminuria, ALT and carotid IMT than TDD for type 2 diabetic patients., Competing Interests: The authors have declared that no competing interests exist.

Objective: The objective of this study was to adapt and validate the Vietnamese version of Active Aging Index (AAI). Method: We conducted an expert panel, focus groups, test-retest and examination of internal consistency, and construct and concurrent validity among 804 older Vietnamese adults. Results: Scale content validity index (CVI) was 0.98. Test-retest coefficients ranged from 0.70 to 1.00. The Cronbach's alphas of well-being, voluntary, affordability, and politics were 0.94, 0.70, 0.65, and 0.16, respectively. Voluntary and well-being had good construct validity. Regarding politics, only one of four items had good test-retest reliability (Kappa 0.84), while other three had low variance in both test-retest and field study. In exploratory factor analysis, items assessing affordability loaded on three components. AAI was positively associated with perceived health, life satisfaction, and quality of life; it was negatively associated with falls, loneliness, and frailty. Discussion: In adapting AAI, researchers should consider cultural sensitivity. Key modifications, findings, explanations, and suggestions are presented here.

Objective: Paclitaxel-coated balloons are used to reduce neointimal hyperplasia in native arteriovenous (AV) fistulas. However, no study specifically evaluated their effect on venous anastomotic stenosis of dialysis grafts. We aimed to compare the efficacy of angioplasty with drug-coated balloons (DCBs) and angioplasty with conventional balloons (CBs) for venous anastomotic stenosis in dysfunctional AV grafts., Methods: In this investigator-initiated, single-center, single-blinded, prospective randomized controlled trial, we randomly assigned 44 patients who had venous anastomotic stenosis to undergo angioplasty with DCBs (n = 22) or CBs (n = 22) from July 2015 to August 2018. Access function was observed per the hemodialysis center's protocols; ancillary angiographic follow-up was performed every 2 months for 1 year after the interventions. The primary end point was target lesion primary patency at 6 months. Secondary outcomes included anatomic and clinical success after angioplasty, circuit primary patency at 6 months and 1 year, and target lesion primary patency at 1 year., Results: At 6 months, target lesion primary patency in the DCB group was significantly greater than that in the CB group (41% vs 9%; hazard ratio [HR], 0.393; 95% confidence interval [CI], 0.194-0.795; P = .006), as was the primary patency of the entire access circuit (36% vs 9%; HR, 0.436; 95% CI, 0.218-0.870; P = .013). At 1 year, the target lesion primary patency in the DCB group remained greater than that in the CB group (23% vs 9%; HR, 0.477; 95% CI, 0.243-0.933; P = .019) but not the primary patency of the access circuit (14% vs 9%; HR, 0.552; 95% CI, 0.288-1.059; P = .056). No difference in anatomic or clinical success was observed; no major complications were noted., Conclusions: Angioplasty with DCBs showed a modest improvement in primary patency of venous anastomotic stenosis and all dialysis AV grafts at 6 months. The short-term benefit was not durable to 1 year, and reinterventions were eventually needed., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) assesses quality of life (QOL) in patients with lung cancer and was the first EORTC module developed for use in international clinical trials. Since its publication in 1994, major treatment advances with possible effects on QOL have occurred. These changes called for an update of the module and its international psychometric validation. We aimed to investigate the scale structure and psychometric properties of the updated lung cancer module, QLQ-LC29, in patients with lung cancer., Methods: This international, observational field study was done in 19 hospitals across 12 countries. Patients aged older than 18 years with a confirmed diagnosis of lung cancer and no other previous primary tumour, and who were mentally fit with sufficient language skills to understand and complete the questionnaire were included. Patients were asked during a hospital visit to fill in the paper versions of the core questionnaire EORTC QLQ-C30 plus QLQ-LC29, and investigators selected half of these patients to complete the questionnaire again 2-4 weeks later. Our primary aim was to assess the scale structure and psychometric properties of EORTC QLQ-LC29. We analysed scale structure using confirmatory factor analysis; reliability using Cronbach's α value (internal consistency) and intra-class coefficient (test-retest reliability); sensitivity using independent t tests stratified by Karnofsky performance status; and responsiveness to change over time by ANOVA. This study is registered with ClinicalTrials.gov, NCT02745691., Findings: Between April 12, 2016, and Sept 26, 2018, 523 patients with a confirmed diagnosis of either non-small-cell lung cancer (n=442) or small-cell lung cancer (n=81) were recruited. Confirmatory factor analysis provided a solution composed of five multi-item scales (coughing, shortness of breath, fear of progression, hair problems, and surgery-related symptoms) plus 15 single symptom or side-effect items: χ 2 =370·233, root mean square error of approximation=0·075, and comparative-fit index=0·901. Cronbach's α for internal consistencies of all multi-item scales were above the threshold of 0·70. Intra-class coefficients for test-retest reliabilities ranged between 0·82 and 0·97. Three (shortness of breath, fear of progression, and hair problems) of the five multi-item scales showed responsiveness to change over time (p values <0·05), as did nine of 15 single symptom items. Four (coughing, shortness of breath, fear of progression, and surgery-related symptoms) of the five multi-item scales and ten of the 15 single symptom items were sensitive to known group differences (ie, lower vs higher Karnofsky performance status)., Interpretation: Results determined the psychometric properties of the updated lung cancer module, which is ready for use in international clinical studies., Funding: EORTC Quality of Life Group., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Restenosis remains a significant problem in endovascular therapy for hemodialysis vascular access. Drug-coated balloon (DCB) angioplasty decreases restenosis in peripheral and coronary artery diseases. The aim of this systematic review and meta-analysis is to assess the patency outcomes following DCB angioplasty, as compared to conventional balloon (CB) angioplasty for the stenosis of hemodialysis vascular access., Methods: A comprehensive search in the MEDLINE, EMBASE, and CENTRAL databases was conducted in order to identify eligible randomized controlled trials evaluating DCB angioplasty for hemodialysis vascular access dysfunction. The primary endpoint was the 6-month target lesion primary patency and the secondary endpoints were 12-month target lesion primary patency and procedure-related complications. Risk ratios (RR) were pooled and relevant subgroups were analyzed separately., Results: Eleven randomized controlled trials comprised of 487 patients treated with DCB angioplasty and 489 patients treated with CB angioplasty were included. There were no significant differences in the target lesion primary patency at 6 months [RR, 0.75; 95% confidence interval (CI), 0.56, 1.01; p = 0.06] and at 12 months (RR 0.89; 95% CI, 0.79, 1.00; p = 0.06). The absence of benefit for the DCB group remained, even in the arteriovenous fistula subgroup or the subgroup of studies excluding central vein stenosis. The risk of procedure-related complication did not differ between the two groups (RR 1.00; 95% CI 0.98, 1.02; p = 0.95)., Conclusion: DCB angioplasty did not demonstrate significant patency benefit for the treatment of hemodialysis vascular access dysfunction. Wide variations in patency outcomes across studies were noted. Further studies focusing on specific types of access or lesions are warranted to clarify the value of DCB for hemodialysis vascular access. (PROSPERO Number CRD42019119938)., Competing Interests: The authors have declared that no competing interests exist.