Search

Background and Objectives: METHODS: A structured search strategy encompassing databases including MEDLINE, Embase, CINAHL Plus, PsycINFO and Cochrane Library was implemented from inception to October 2023. Included studies focused on interventions targeting opioid reduction in adults following major surgeries. The risk of bias was evaluated using Cochrane risk-of-bias tool V.2 (RoB 2) and non-randomised studies of interventions (ROBINS-I) tools, and Cohen's d effect sizes were calculated. BCTs were identified using a validated taxonomy., Results: 22 studies, comprising 7 clinical trials and 15 cohort studies, were included, with varying risks of bias. Educational (n=12), guideline-focused (n=3), multifaceted (n=5) and pharmacist-led (n=2) interventions demonstrated diverse effect sizes (small-medium n=10, large n=12). A total of 23 unique BCTs were identified across studies, occurring 140 times. No significant association was observed between the number of BCTs and effect size, and interventions with large effect sizes predominantly targeted healthcare professionals. Key BCTs in interventions with the largest effect sizes included behaviour instructions, behaviour substitution, goal setting (outcome), social support (practical), social support (unspecified), pharmacological support, prompts/cues, feedback on behaviour, environmental modification, graded tasks, outcome goal review, health consequences information, action planning, social comparison, credible source, outcome feedback and social reward., Conclusions: Understanding the dominant BCTs in highly effective interventions provides valuable insights for future opioid tapering strategy implementations. Further research and validation are necessary to establish associations between BCTs and effectiveness, considering additional influencing factors., Prospero Registration Number: CRD42022290060., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The out-of-control action plan (OCAP) is crucial in the wafer probing process of semiconductor manufacturing as it systematically addresses and corrects deviations, ensuring the high quality and reliability of semiconductor devices. However, the traditional OCAP involves many redundant and complicated processes after failures occur on production lines, which can delay production and escalate costs. To overcome the traditional OCAP's limitations, this paper proposes a novel OCAP aimed at enhancing the wafer probing process in semiconductor manufacturing. The proposed OCAP integrates proactive measures such as preventive maintenance and advanced monitoring technologies, which are tested and verified through a comprehensive experimental setup. Implementing the novel OCAP in a case company's production line reduced machine downtime by over 24 h per week and increased wafer production by about 23 wafers per week. Additionally, probe test yield improved by an average of 1.1%, demonstrating the effectiveness of the proposed method. This paper not only explores the implementation of the novel OCAP but also compares it with the traditional OCAP, highlighting significant improvements in efficiency and production output. The results underscore the potential of advanced OCAP to enhance manufacturing processes by reducing dependency on human judgment, thus lowering the likelihood of errors and improving overall equipment effectiveness (OEE).

Background: This prospective study aimed to explore the effectiveness of an oral care intervention with Tegaderm on the oral mucosal health of intubated patients., Methods: A total of 70 intubated patients were included and randomly assigned to 1 of 3 groups, clean water brushing teeth (n = 23), brushing teeth combined with mouthwash (BTM) (n = 23), and brushing teeth combined with mouthwash and Tegaderm (BTMT) (n = 24). The Oral Mucositis Assessment Scale (OMAS) was applied to evaluate the patient's oral mucosal health before and after oral care intervention., Results: The BTMT group had lower OMAS scores in almost all regions of the oral cavity, compared to the brushing teeth and BTM groups. The general linear model for repeated measurement indicated the BTMT group had the lowest total OMAS scores from Day 2 to Day 4 after the initiation of baseline OMAS evaluation. Of the 3 intervention groups, the BTMT group had the shortest length of endotracheal intubation. The BTMT group had the lowest incidence rate of ventilator-associated pneumonia; however, no significant between-group differences were found., Conclusions: BTMT effectively reduced the decline in oral mucosal health that was caused by endotracheal intubation and shortened the length of endotracheal intubation., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Professional self-concept consists of one's judgments, attitudes about oneself professionally, and one's own perception as a professional. A positive professional self-concept can support students and new nurses throughout their nursing careers., Objective: To describe levels of self-concept among pre-licensure undergraduate students., Participants/setting: The participants were nursing students in a Bachelor of Science in Nursing program in the United States., Design/methods: This is a cross-sectional correlational study with self-report instruments, including demographics and the Professional Self-Concept of Nurses Instrument. Data (N = 103) were analyzed with SPSS/WIN 29.0. Descriptive statistics and professional self-concept scores were examined with independent t-tests, ANOVA, and Pearson's correlations., Results: Most participants were female (n = 90), with a mean age of 20 years (SD = 1). The mean professional self-concept of nurses score was 78 (SD = 7), ranging from 27 to 108, and professional self-concept was positively correlated with receiving tutoring through the university's program, working as a tutor for nursing students or students in prerequisite classes, transferring into the nursing program, and participating in campus nursing organizations. Professional self-concept was negatively correlated with advancement in semesters of the nursing program, being a first-generation college student, having a family member who is a nurse, GPA, and having clinical-related work experience in healthcare., Conclusions: Higher levels of exposure to nursing may be related to lower professional self-concept. This is important to recognize and it may generalize to other nursing schools and health-related departments. Schools of nursing should enhance students' resilience by promoting self-concept. Our findings also shade light on self-care and the mental health of healthcare professionals., Competing Interests: Declaration of competing interest Nothing to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Intestinal parasitic infections are the most common infectious diseases among Southeast Asian migrant workers in Taiwan, especially for infections with Blastocystis hominis. However, little is known about the impact of Blastocystis subtypes (STs) on the gut microbiota., Methods: We retrospectively evaluated the prevalence of intestinal parasites in a teaching hospital in Northern Taiwan in the period of 2015-2019. Blastocystis-positive stool specimens were collected for ST analysis by polymerase chain reaction in 2020. Intestinal microbiota analyses of different Blastocystis STs and Blastocystis-free individuals were conducted by 16S rRNA sequencing., Results: A total of 13,859 subjects were analyzed, of which 1802 cases (13%) were diagnosed with intestinal parasitic infections. B. hominis infections were the most prevalent (n = 1546, 85.7%). ST analysis of Blastocystis-positive samples (n = 150) indicated that ST1 was the most common type, followed by ST3, ST4, ST2, ST7, and ST5. Different Blastocystis STs (ST1, ST3, and ST4) were associated with distinct richness and diversity of the microbiota. Taxonomic profiles revealed that Akkermansia muciniphila was significantly enriched for all analyzed Blastocystis STs, whereas Holdemanella biformis was more abundant in the Blastocystis-free group. Additionally, Succinivibrio dextrinosolvens and Coprococcus eutactus were specifically more abundant in ST3 carriers than in non-infected individuals., Conclusion: This study demonstrates that A. muciniphila is positively associated with all Blastocystis STs, while H. biformis was negatively associated with them. Several bacteria were enriched in specific STs, highlighting the need for further microbiota analysis at the ST level to elucidate the pathogenicity of Blastocystis., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (© 2023 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

The lack of intrinsic active sites for photocatalytic CO 2 reduction reaction (CO 2 RR) and fast recombination rate of charge carriers are the main obstacles to achieving high photocatalytic activity. In this work, a novel phosphorus and boron binary-doped graphitic carbon nitride, highly porous material that exhibits powerful photocatalytic CO 2 reduction activity, specifically toward selective CO generation, is disclosed. The coexistence of Lewis-acidic and Lewis-basic sites plays a key role in tuning the electronic structure, promoting charge distribution, extending light-harvesting ability, and promoting dissociation of excitons into active carriers. Porosity and dual dopants create local chemical environments that activate the pyridinic nitrogen atom between the phosphorus and boron atoms on the exposed surface, enabling it to function as an active site for CO 2 RR. The P-N-B triad is found to lower the activation barrier for reduction of CO 2 by stabilizing the COOH reaction intermediate and altering the rate-determining step. As a result, CO yield increased to 22.45 µmol g -1  h -1 under visible light irradiation, which is ≈12 times larger than that of pristine graphitic carbon nitride. This study provides insights into the mechanism of charge carrier dynamics and active site determination, contributing to the understanding of the photocatalytic CO 2 RR mechanism., (© 2024 Wiley‐VCH GmbH.)

Lymphoproliferative disorders (LPD) comprise a heterogeneous group and are originally classified into the "Disease of immune dysregulation" category. Of 96 Taiwanese patients during 2003-2022, 31 (median 66, range 0.03-675 months) developed LPD, mainly including palpable lymphadenopathy (in 10 patients), intestinal lymphadenopathy associated with refractory inflammatory bowel disease (IBD in 8) and hepatosplenomegaly (in 7) during long-term follow-up (median 144, range 3-252 months). They distributed in the categories of antibody deficiency (2 CVID, 2 TTC37, PIK3CD, PIK3R1 and AICDA each), phagocyte (4 CYBB, 1 STAT1 and 1 IFNRG1), immune dysregulation (2 FOXP3, 2 XIAP and 2 HLH), combined immunodeficiencies (2 IL2RG; CD40L, ZAP70 and unknown each), syndromic features (2 STAT3-LOF, 1 WAS and 1 ATM) and three with anti-IFN-γ autoantibodies. An increased senescent (CD8 + CD57+) and CD21-low, disturbed transitional B (CD38 + IgM++), plasmablast B (CD38++IgM-), memory B (CD19 + CD27+) and T EMRA (CD27-IgD-) components were often observed in cross-sectional immunophenotyping and trended to develop LPD., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

An electrochemical capacitor configuration extends its operational potential window by leveraging diverse charge storage mechanisms on the positive and negative electrodes. Beyond harnessing capacitive, pseudocapacitive, or Faradaic energy storage mechanisms and enhancing electrochemical performance at high rates, achieving a balance of stored charge across electrodes poses a significant challenge over a wide range of charge-discharge currents or sweep rates. Consequently, fabricating hybrid and asymmetric supercapacitors demands precise electrochemical evaluations of electrode materials and the development of a reliable methodology. This work provides an overview of fundamental aspects related to charge-storage mechanisms and electrochemical methods, aiming to discern the contribution of each process. Subsequently, the electrochemical properties, including the working potential windows, rate capability profiles, and stabilities, of various families of electrode materials are explored. It is then demonstrated, how charge balancing between electrodes falters across a broad range of charge-discharge currents or sweep rates. Finally, a methodology for achieving charge balance in hybrid and asymmetric supercapacitors is proposed, outlining multiple conditions dependent on loaded mass and charge-discharge current. Two step-by-step tutorials and model examples for applying this methodology are also provided. The proposed methodology is anticipated to stimulate continued dialogue among researchers, fostering advancements in achieving stable and high-performance supercapacitor devices., (© 2024 Wiley‐VCH GmbH.)

Best practices in postpartum care encourage rooming-in to promote early breastfeeding and mother-newborn bonding. However, when the medical records of mothers and newborns are stored separately in the postpartum ward and the neonatal nursery, respectively, nurses encounter difficulties in accessing complete information about the mother-infant dyad, which results in suboptimal care quality. Accordingly, the authors designed an integrated electronic information (e-information) system linking the medical records of newborns and their mothers and implemented it in April 2022 at a medical center in Taiwan. System effectiveness assessment results indicated that before the implementation of the e-information system, the nursing care completion scored 72.4 out of 100, and the nurse satisfaction scored 80.9 out of 100. After the implementation of the system, the nursing care completion increased to 97.8 (p < .001), while the nurse satisfaction rose to 95.8 (p < .001), demonstrating significant improvements.

Objectives: Dihydroisotanshinone I (DT) is a kind of diterpenoid compound extracted from the dried roots of Salvia miltiorrhiza Bunge, and exhibits multiple biological activities including anti-tumor activity. Cisplatin is one of the first-line drugs for the treatment of lung adenocarcinoma (LAUD), but the drug resistance and toxicity limit its efficacy. DT is known to induce apoptosis and ferroptosis, but it is unclear whether DT can inhibit the cisplatin-resistant LAUD cells and reverse the drug resistance in LAUD. Therefore, our study intends to establish the cisplatin-resistant human LAUD cells (A549/DDP), and figure out the influence and related mechanisms of DT reversing cisplatin resistance in A549/DDP cells, so as to provide a theoretical basis for the DT as a new natural candidate for the treatment of LAUD., Methods: The establishment of A549/DDP was the continuous stimulation by exposing A549 to gradient concentrations of Cisplatin. The cell viability of A549 and A549/DDP was detected by CCK-8 kit, and the IC50 value was calculated. The morphological changes of A549 and A549/DDP cells were observed by an inverted microscope. The contents of malondialdehyde (MDA) and glutathione (GSH) in A549/DDP cells after drug treatment were detected by related kits. The levels of Fe2+, cytosolic reactive oxygen species (ROS), and lipid reactive oxygen species (lipid ROS) were detected by a fluorescence microplate reader or fluorescence cell imager according to the related fluorescent probe kit instructions. Western blot was used to detect the expressions of PI3K, phospho-PI3K, AKT, phospho-AKT, MDM2, p53, GPX4, and SLC7A11 in A549/DDP after different drug treatments., Key Findings: Our study demonstrated that the inhibitory effect of DT on A549 and A549/DDP cells was time-dependent and concentration-dependent, and DT and DDP had a synergistic effect on inhibiting the proliferation of A549/DDP cells. Furthermore, DT mainly induced ferroptosis in A549/DDP cells and synergized with cisplatin to promote ferroptosis in A549/DDP cells. The result of KEGG pathway analysis, molecular docking and western blot showed that DT could enhance the cisplatin sensitivity of A549/DDP by inhibiting PI3K/MDM2/P53 signaling pathway., Conclusions: Consequently, we concluded that DT promotes ferroptosis in cisplatin-resistant LAUD A549/DDP cells. Additionally, DT reverses cisplatin resistance by promoting ferroptosis via PI3K/MDM2/P53 pathway in A549/DDP cells., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The NLRP3 inflammasome is an essential component of the innate immune system, but excessive activation can lead to inflammatory diseases. Ion fluxes across the plasma membrane or from intracellular stores are known to regulate NLRP3 inflammasome activation. Deep-sea water (DSW) contains high concentrations of many mineral ions, which could potentially influence NLRP3 inflammasome activation. However, the impact of DSW on NLRP3 inflammasome activation has not been investigated. Here, we demonstrated that DSW with water hardness levels up to 500 mg/L did not affect cell viability or the expression of NLRP3 inflammasome components in macrophages derived from THP-1 cells. However, the DSW significantly inhibited IL-1β secretion and caspase-1 activation in response to NLRP3 activators such as nigericin, ATP, or monosodium urate (MSU) crystals. Mechanically, it was discovered that the presence of 5 mM magnesium ions (Mg2 + ), equivalent to the Mg2 + concentration found in the DSW with a water hardness of 500 mg/L, inhibits NLRP3 inflammasome activation. This indicates that Mg2 + contributes to the mechanism by which DSW mitigates NLRP3 inflammasome activation. Moreover, DSW administration effectively lessens MSU-triggered peritonitis in mice, a commonly used model for examining the impacts of NLRP3 inflammasome activation. These results show that DSW enriched with Mg 2+ could potentially be beneficial in modulating NLRP3 inflammasome-associated diseases., Competing Interests: 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., (© 2024 The Authors.)

This meta-analysis investigated the effects of intravenous magnesium sulfate on the postoperative recovery quality, as assessed using the Quality of Recovery (QoR) questionnaire, in adult surgical patients. Seven randomized controlled trials involving 622 patients were included. Compared with the placebo, magnesium sulfate significantly improved the global QoR score on postoperative day 1 (standardized mean difference [SMD]: 1.24; 95% confidence interval: 0.70-1.78; p < 0.00001). It also enhanced specific QoR dimensions, with substantial effects on pain (SMD: 1, p < 0.00001) and physical comfort (SMD: 0.85, p < 0.0001), a moderate effect on emotional state (SMD: 0.65, p = 0.002), and small improvements in physical independence (SMD: 0.43, p < 0.00001) and psychological support (SMD: 0.37, p < 0.0001). In addition, magnesium sulfate reduced the intraoperative opioid consumption (SMD: -0.66, p < 0.0001), postoperative pain severity, and the incidence of postoperative nausea and vomiting (risk ratio: 0.48, p = 0.008). The extubation times were unaffected, whereas the post-anesthesia care unit stay was slightly prolonged. These findings highlight the potential of magnesium sulfate as a valuable adjunct for multimodal analgesia and enhanced recovery. Future studies should aim to elucidate the optimal dosing strategies, timing of administration, and specific surgical populations that may derive maximum benefits.

Eliminating the core fucose from the N -glycans of the Fc antibody segment by pathway engineering or enzymatic methods has been shown to enhance the potency of therapeutic antibodies, especially in the context of antibody-dependent cytotoxicity (ADCC). However, there is a significant challenge due to the limited defucosylation efficiency of commercially available α-l-fucosidases. In this study, we report a unique α-l-fucosidase ( Pn fucA) from the bacterium Prevotella nigrescens that has a low sequence identity compared with all other known α-l-fucosidases and is highly reactive toward a core disaccharide substrate with fucose α(1,3)-, α (1,4)-and α(1,6)-linked to GlcNAc, and is less reactive toward the Fuc-α(1,2)-Gal on the terminal trisaccharide of the oligosaccharide Globo H (Bb3). The kinetic properties of the enzyme, such as its K m and k cat , were determined and the optimized expression of Pn fucA gave a yield exceeding 30 mg/L. The recombinant enzyme retained its full activity even after being incubated for 6 h at 37 °C. Moreover, it retained 92 and 87% of its activity after freezing and freeze-drying treatments, respectively, for over 28 days. In a representative glycoengineering of adalimumab (Humira), Pn fucA showed remarkable hydrolytic efficiency in cleaving the α(1,6)-linked core fucose from FucGlcNAc on the antibody with a quantitative yield. This enabled the seamless incorporation of biantennary sialylglycans by Endo-S2 D184 M in a one-pot fashion to yield adalimumab in a homogeneous afucosylated glycoform with an improved binding affinity toward Fcγ receptor IIIa.

Background: The inclusion of a connecting path in a porous implant can promote nutrient diffusion to cells and enhance bone ingrowth. Consequently, this study aimed to evaluate the biomechanical, radiographic, and histopathological performance of a novel 3D-printed porous suture anchor in a rabbit femur model., Methods: Three test groups were formed based on the type of suture anchor (SA): Commercial SA (CSA, Group A, n = 20), custom solid SA (CSSA, Group B, n = 20), and custom porous SA (CPSA, Group C, n = 20). The SAs were implanted in the lateral femoral condyle of the right leg in each rabbit. The rabbits (New Zealand white rabbits, male, mean body weight of 2.8 ± 0.5 kg, age 8 months) underwent identical treatment and were randomized into experimental and control groups via computer-generated randomization. Five rabbits (10 femoral condyles) were euthanized at 0, 4, 8, and 12 weeks post-implantation for micro-CT, histological analysis, and biomechanical testing., Results: At 12 weeks, the CPSA showed a higher BV/TV (median 0.7301, IQR 0.7276-0.7315) than the CSSA and CSA. The histological analysis showed mineralized osteocytes near the SA. At 4 weeks, new bone was observed around the CPSA and had penetrated its porous structure. By 12 weeks, there was no significant difference in ultimate failure load between the CSA and CPSA., Conclusions: We demonstrated that the innovative 3D-printed porous suture anchor exhibited comparable pullout strength to conventional threaded suture anchors at the 12-week postoperative time-point period. Furthermore, our porous anchor design enhanced new bone formation and facilitated bone growth into the implant structure, resulting in improved biomechanical stability., (© 2024. The Author(s).)

Black GaAs nanotip arrays (NTs) with 3300 nm lengths were fabricated via self-masked plasma etching. We show, both experimentally and numerically, that these NTs, with three gradient refractive index layers, effectively suppress Fresnel reflections at the air-GaAs interface over a broad range of wavelengths. These NTs exhibit exceptional UV-Vis light absorption (up to 99%) and maintain high NIR absorption (33-60%) compared to bare GaAs. Moreover, possessing a graded layer with a low refractive index (n = 1.01 to 1.12), they achieve angular and polarization-independent antireflection properties exceeding 80° at 632.8 nm, aligning with perfect antireflective coating theory predictions. This approach is anticipated to enhance the performance of optoelectronic devices across a wide range of applications.

Competing Interests: None disclosed.

Aiming at the problems of high stochasticity and volatility of power loads as well as the difficulty of accurate load forecasting, this paper proposes a power load forecasting method based on CEEMDAN (Completely Integrated Empirical Modal Decomposition) and TCN-LSTM (Temporal Convolutional Networks and Long-Short-Term Memory Networks). The method combines the decomposition of raw load data by CEEMDAN and the spatio-temporal modeling capability of TCN-LSTM model, aiming to improve the accuracy and stability of forecasting. First, the raw load data are decomposed into multiple linearly stable subsequences by CEEMDAN, and then the sample entropy is introduced to reorganize each subsequence. Then the reorganized sequences are used as inputs to the TCN-LSTM model to extract sequence features and perform training and prediction. The modeling prediction is carried out by selecting the electricity compliance data of New South Wales, Australia, and compared with the traditional prediction methods. The experimental results show that the algorithm proposed in this paper has higher accuracy and better prediction effect on load forecasting, which can provide a partial reference for electricity load forecasting methods., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Heng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: None disclosed.

Objectives: Esophagectomy after chemoradiotherapy is associated with an increased risk of surgical complications. The significance of preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio after chemoradiotherapy in predicting pulmonary complications following radical esophagectomy in esophageal squamous cell carcinoma patients receiving preoperative chemoradiotherapy remains unknown. We aimed to investigate the utility of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in predicting the pulmonary complications of esophagectomy after preoperative chemoradiotherapy., Methods: We retrospectively reviewed 111 consecutive patients with stage III esophageal squamous cell carcinoma who received preoperative chemoradiotherapy followed by esophagectomy between January 2009 and December 2017. Laboratory data were collected before the operation and surgical outcomes and complications were recorded. We calculated neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and correlated them with the clinical parameters, postoperative complications, overall survival, and disease-free survival., Results: Postoperative complications were observed in 75 (68%) patients, including 32 (29%) with pulmonary complications. The preoperative neutrophil-to-lymphocyte ratio of ≥ 3 (P = 0.008), clinical T4 classification (P = 0.007), and advanced stage IIIC (P = 0.012) were significantly associated with pulmonary complications. Pulmonary complication rates were 15% and 38% in patients with preoperative neutrophil-to-lymphocyte ratio of < 3 and ≥ 3, respectively. Preoperative neutrophil-to-lymphocyte ratio was not associated with the oncological stratification such as pathological T classification, pathological N classification, and pathological AJCC stage. The 3-year overall survival rates were 70% and 34% in patients with preoperative neutrophil-to-lymphocyte ratio of < 3 and ≥ 3, respectively (P = 0.0026). The 3-year disease-free survival rates were 57% and 29% in patients with preoperative neutrophil-to-lymphocyte ratio of < 3 and ≥ 3, respectively (P = 0.0055). The preoperative neutrophil-to-lymphocyte ratio of ≥ 3 was independently associated with more pulmonary complications, inferior overall survival, and worse disease-free survival., Conclusions: Elevated preoperative neutrophil-to-lymphocyte ratio after chemoradiotherapy is independently associated with higher pulmonary complication rate following radical esophagectomy and poor prognosis in patients with esophageal squamous cell carcinoma receiving preoperative chemoradiotherapy. Preoperative neutrophil-to-lymphocyte ratio is routinely available in clinical practice and our findings suggest it can be used as a predictor for pulmonary complications after esophagectomy in patients with esophageal squamous cell carcinoma receiving preoperative chemoradiotherapy., (© 2024. The Author(s).)

In a high-pressure environment, electrospray ionization (ESI) can be achieved without discharge between the emitter and the counter electrode, thus enabling the generation of gas-phase ions from liquid with high surface tension, such as pure water, which requires a high onset voltage for stable ESI. In this study, the ion dissociation during the transferring of ions/charged droplets from a superatmospheric pressure environment to vacuum has been systematically investigated using benzyl ammonium thermometer ions. The ion source pressure did not affect the internal energy distribution of ions, whereas the gas throughput into the first vacuum stage clearly influences the internal energy distribution of the ions. The increase in the gas throughput increased the density of molecules/atoms presented in ion transfer/focusing electrodes located in the first vacuum stage. As a result, the mean free path of ions in the first vacuum stage decreases, and the energy of ions decreases by decreasing the kinetic energy involved in each collision between ions and residue gas. The gas throughput into the first vacuum stage is found to describe the internal energy distribution of ions associated with the local conditions more quantitatively instead of using the measured pressure of the vacuum stage, which is different from the effective local pressure. This study also demonstrated the controlled dissociation of ions using the ion transfer settings of the instrument in combination with ion inlet tubes of different sizes.

Objective: To assess the treatment efficacy of dienogest specifically in the Taiwanese population with endometriosis., Materials and Methods: Eighty-eight patients diagnosed with endometriosis receiving at least 3 months of dienogest 2 mg once daily, from January 2018 to June 2022, were enrolled. They were divided into two groups: surgery group and non-surgery group. The assessment of pain improvement was based on visual analog scale (VAS) scores (0-100 mm) recorded at 0, 3, 6, and 12 months following the initiation of dienogest. Serum CA-125 value and ovarian endometrioma size were analyzed at 0 and 6 months., Results: A total of 65 patients with endometriosis presented painful symptoms. In the surgery group (N = 28), the initial VAS score was 47.5 mm, which significantly declined to 9.6 mm at 3 months (p < 0.01), then to 7.5 mm, 2.9 mm, and 2.1 mm at 6, 9, and 12 months, respectively. In the non-surgery group (N = 37), the initial VAS score was 65.7 mm, which significantly declined to 13.2 mm at 3 months (p < 0.01) and 4.9 mm at 6 months (p < 0.05), remained low at 0.3 mm at both 9 and 12 months. Endometrioma size (N = 33) exhibited a significant 35% decrease from 38.2 mm to 24.8 mm after 6 months treatment (p < 0.01). Serum CA-125 levels showed significant improvement from 86.5 to 30.2 U/ml (p < 0.01) at 6 months., Conclusion: This retrospective cohort study proved that dienogest is effective in reducing endometriosis-associated pain and endometrioma size in Taiwanese population., Competing Interests: Conflict of interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Chondrosarcoma is a malignant bone tumor that arises from abnormalities in cartilaginous tissue and is associated with lung metastases. Extracellular vesicles called exosomes are primarily used as mediators of intercellular signal transmission to control tumor metastasis. Visfatin is an adipokine reported to enhance tumor metastasis, but its relationship with exosome generation in chondrosarcoma motility remains undetermined. Our results found that overexpressing visfatin augments the production of exosomes from chondrosarcoma cells. Visfatin-treated chondrosarcoma exosomes educate macrophage polarization towards the M2 but not M1 phenotype. Interestingly, M2 macrophages polarized by exosomes return to chondrosarcoma cells to facilitate cell motility. According to these findings, chondrosarcoma cells emit more exosomes when treated with visfatin. The stimulation of exosome generation by visfatin polarizes M2 macrophages and enhances the motility of chondrosarcoma., (© 2024 Wiley Periodicals LLC.)

Background: Daptomycin is widely used in critically ill patients for Gram-positive bacterial infections. Extracorporeal membrane oxygenation (ECMO) is increasingly used in this population and can potentially alter the pharmacokinetic (PK) behaviour of antibiotics. However, the effect of ECMO has not been evaluated in daptomycin. Our study aims to explore the effect of ECMO on daptomycin in critically ill patients through population pharmacokinetic (PopPK) analysis and to determine optimal dosage regimens based on both efficacy and safety considerations., Methods: A prospective, open-label PK study was carried out in critically ill patients with or without ECMO. The total concentration of daptomycin was determined by UPLC-MS/MS. NONMEM was used for PopPK analysis and Monte Carlo simulations., Results: Two hundred and ninety-three plasma samples were collected from 36 critically ill patients, 24 of whom received ECMO support. A two-compartment model with first-order elimination can best describe the PK of daptomycin. Creatinine clearance (CLCR) significantly affects the clearance of daptomycin while ECMO has no significant effect on the PK parameters. Monte Carlo simulations showed that, when the MICs for bacteria are  ≥1 mg/L, the currently recommended dosage regimen is insufficient for critically ill patients with CLCR > 30 mL/min. Our simulations suggest 10 mg/kg for patients with CLCR between 30 and 90 mL/min, and 12 mg/kg for patients with CLCR higher than 90 mL/min., Conclusions: This is the first PopPK model of daptomycin in ECMO patients. Optimal dosage regimens considering efficacy, safety, and pathogens were provided for critical patients based on pharmacokinetic-pharmacodynamic analysis., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Synthetic cathinones have gained increasing popularity in the illicit drug market, yet their abuse potential remains poorly understood. In this study, zebrafish were used to compare the addictive potential of three cathinone analogs, namely pentylone, eutylone, and N-ethylpentylone (NEP). The zebrafish received various doses (0 to 60 mg/kg) of the cathinone analogs by oral gavage over two sessions per day for two consecutive days to induce conditioned place preference (CPP). Pentylone, eutylone, and NEP dose-dependently induced CPP, with NEP showing significantly higher CPP than pentylone and eutylone at the dose of 20 mg/kg. The fish that received 60 mg/kg of cathinones underwent extinction, followed by reinstatement triggered by drug priming. NEP required six sessions to meet the criteria of extinction, followed by eutylone, which required four sessions, and pentylone, which required three sessions. Furthermore, NEP and eutylone at a dose of 40 mg/kg could reinstate the extinguished CPP, while 60 mg/kg of pentylone was necessary for CPP reinstatement. The persistence of susceptibility to reinstatement was also assessed at 7 and 14 days after the initial reinstatement. The CPP induced by all three cathinone analogs could be reinstated 7 days after the initial reinstatement, whereas only CPP induced by NEP, but not pentylone and eutylone, could be reinstated again after 14 days. Considering the potency to induce CPP, resistance to extinction, and the propensity for reinstatement, the abuse liability rank order of the cathinone analogs might be as follows: NEP > eutylone > pentylone. These findings suggest that the zebrafish CPP paradigm can serve as a viable model for assessing the relative abuse liability of substances.

Objective: In this study, we used a bibliometric and visual analysis to evaluate the characteristics of the 100 most cited articles on axon regeneration., Methods: The 100 most cited papers on axon regeneration published between 2003 and 2023 were identified by searching the Web of Science Core Collection database. The extracted data included the title, author, keywords, journal, publication year, country, and institution. A bibliometric analysis was subsequently undertaken., Results: The examined set of 100 papers collectively accumulated a total of 39,548 citations. The number of citations for each of the top 100 articles ranged from 215 to 1,604, with a median value of 326. The author with the most contributions to this collection was He, Zhigang, having authored eight papers. Most articles originated in the United States ( n  = 72), while Harvard University was the institution with the most cited manuscripts ( n  = 19). Keyword analysis unveiled several research hotspots, such as chondroitin sulfate proteoglycan, alternative activation, exosome, Schwann cells, axonal protein synthesis, electrical stimulation, therapeutic factors, and remyelination. Examination of keywords in the articles indicated that the most recent prominent keyword was "local delivery.", Conclusion: This study offers bibliometric insights into axon regeneration, underscoring that the United States is a prominent leader in this field. Our analysis highlights the growing relevance of local delivery systems in axon regeneration. Although these systems have shown promise in preclinical models, challenges associated with long-term optimization, agent selection, and clinical translation remain. Nevertheless, the continued development of local delivery technologies represents a promising pathway for achieving axon regeneration; however, additional research is essential to fully realize their potential and thereby enhance patient outcomes., Competing Interests: The 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 Saijilafu, Ye, Zhang and Xu.)

The Diels-Alder reaction is one of the most effective methods for the synthesis of substituted cyclohexenes. The development of protein catalysts for this reaction remains a major priority, affording new sustainable routes to high value target molecules. Whilst a small number of natural enzymes have been shown capable of catalysing [4 + 2] cycloadditions, there is a need for significant mechanistic understanding of how these prospective Diels-Alderases promote catalysis to underpin their development as biocatalysts for use in synthesis. Here we present a molecular description of the complete reaction cycle of the bona fide natural Diels-Alderase AbyU, which catalyses formation of the spirotetronate skeleton of the antibiotic abyssomicin C. This description is derived from X-ray crystallographic studies of AbyU in complex with a non-transformable synthetic substrate analogue, together with transient kinetic analyses of the AbyU catalysed reaction and computational reaction simulations. These studies reveal the mechanistic intricacies of this enzyme system and establish a foundation for the informed reengineering of AbyU and related biocatalysts., Competing Interests: The authors declare that they have no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Background: The interplay between diabetes mellitus (DM), glycemic traits, and vascular and valvular calcifications is intricate and multifactorial. Exploring potential mediators may illuminate underlying pathways and identify novel therapeutic targets., Methods: We utilized univariable and multivariable Mendelian randomization (MR) analyses to investigate associations and mediation effects. Additionally, the multivariable MR analyses incorporated cardiometabolic risk factors, allowing us to account for potential confounders., Results: Type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c) were positively associated with both coronary artery calcification (CAC) and calcific aortic valvular stenosis (CAVS). However, fasting glucose (FG) was only linked to CAVS and showed no association with CAC. Additionally, CAVS demonstrated a causal effect on FG. Calcium levels partially mediated the impact of T2DM on both types of calcifications. Specifically, serum calcium was positively associated with both CAC and CAVS. The mediation effects of calcium levels on the impact of T2DM on CAC and CAVS were 6.063% and 3.939%, respectively. The associations between T2DM and HbA1c with calcifications were influenced by body mass index (BMI) and smoking status. However, these associations were generally reduced after adjusting for hypertension., Conclusion: Our findings suggest a genetically supported causal relationship between DM, glycemic traits, and vascular and valvular calcifications, with serum calcium playing a critical mediating role., (© 2024. The Author(s).)

Background and Purpose: Parents of preterm infants experience anxiety and stress in the neonatal intensive care unit (NICU). Visitation restrictions due to COVID-19 have increased maternal pressure and limited bonding opportunities. Little research exists in Taiwan on using video conferencing as a solution. This study investigates depression and stress levels in mothers of preterm infants and evaluates the effectiveness of video visitation during NICU restrictions., Methods: This study adopts a cross-sectional design and a qualitative survey. Mothers of premature infants were recruited and they participated in the study. Interventions for video visits were scheduled on the third day of admission to the NICU (T1) and during the second week of the study (T2). After each video visit, participants completed an online survey. The study's online survey used structured questionnaires including demographics, the Edinburgh Postnatal Depression Scale (EPDS) and the Parental Stress Scale (PSS): Infant Hospitalization (IH)., Results: A total of 51 mothers of preterm infants participated in the study. During the T1 and T2 periods, single mothers with lower educational levels and those aged below 30 experienced depression and high levels of stress. Lower birth weight and gestational age were associated with maternal depression. Video visitation intervention led to a significant decrease in depression scores (EPDS, T1: 11.3 ± 5.5 vs. T2: 10.1 ± 5.2, p = 0.039). Positive correlations were observed between EPDS and PSS: IH scores (p < 0 .005)., Conclusion: Video visitation intervention can reduce maternal depression in mothers with preterm infants. Since it is practical, video visitation may be applied even after the pandemic., Competing Interests: Declaration of competing interest The authors declare there are no conflicts of interest., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

All-inorganic perovskites show great promise as an emission layer in perovskite light-emitting diodes (PeLEDs) owing to their easy solution processing, low manufacturing cost, and excellent optoelectronic properties. However, there is still an immense performance gap from small-area devices to large-area PeLED devices. The inhomogeneity of large-area high-quality perovskite films inevitably leads to vast defects and electroluminescence performance losses. Herein, a post-hot-cast annealing deposition scheme and the introduction of the multifunctional molecule 2-amino-1,3-propanediol (APDO) were proposed to regulate the crystallization of the perovskite film. As a result, uniform APDO:CsPbBr 2.5 Cl 0.5 perovskite films with high crystallinity and lower defect density were deposited by post-hot-cast annealing. A decent maximum brightness of 2659 cd m -2 was achieved for the large-area cyan PeLEDs with an emitting area of 400 mm 2 ., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

Selective synthesis of chiral bridged (hetero)bicyclic scaffolds via asymmetric C-H activation constitutes substantial challenges due to the multiple reactivities of strained bicyclic structures. Herein, we develop the domino transformations through an unprecedented cobalt-catalyzed enantioselective C-H activation/nucleophilic [3 + 2] annulation with symmetrical bicyclic alkenes. The methods offer straightforward access to a wide range of chiral molecules bearing [2.2.1]-bridged bicyclic cores with four and five consecutive stereocenters in a single step. Two elaborate salicyloxazoline (Salox) ligands were synthesized based on the rational design and mechanistic understanding. The well-defined chiral pockets generated from asymmetric coordination around the trivalent cobalt catalyst direct the orientation of bicyclic alkenes, leading to excellent enantioselectivity.

Introduction: Tyrosine kinase inhibitors (TKIs) have been used as the first-line treatment for many patients with renal cell carcinoma (RCC), the seventh most common cancer in the United Kingdom. However, suboptimal adherence to TKIs can result in poor clinical prognosis. This study quantified RCC patients' adherence to TKIs and explored factors associated with suboptimal adherence., Method: This retrospective cohort study was conducted at a specialist oncology tertiary hospital in Northwest England, using pharmacy dispensing records between November 2021 and March 2022. TKI prescriptions dispensed to patients with RCC were extracted to calculate the persistency gaps (≥7 or ≥14 days) and medication possession ratio (MPR). Multilevel regression analysis was conducted to associate MPR and persistency gaps with specific patient-related and TKI-related factors. This study did not require ethics approval., Results: Of the 2225 prescriptions dispensed to 109 patients, 469 (23.4%) and 274 (13.7%) persistency gaps of ≥7 and ≥14 days were identified. About 75% and 92% of patients had a persistency gap of ≥7 days within the first 90 days and 180 days. The length of time since the first TKI prescription ( p  < 0.001) and the use of sunitinib( p  = 0.003) were significantly associated with the number of prescription gaps of ≥7 days. Moreover, the median MPR was 95.6% (interquartile range: 90.7%, 100.1%). Similarly, the length of time since the first TKI prescription was dispensed ( p  < 0.001) and the use of sunitinib ( p  = 0.034) were significantly associated with MPR., Discussion and Conclusion: This single-centre study found that patients with RCC generally adhere to TKIs (MPR > 90%), but many patients experienced a persistency gap. The crucial window to mitigate TKI utilisation is within 180 days after the initial dispensing of TKIs. Further large-scale studies are required to comprehensively investigate other factors associated with adherence to TKIs and develop interventions to improve adherence and medication use problems., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Substantial data support a heritable basis for supraventricular tachycardias, but the genetic determinants and molecular mechanisms of these arrhythmias are poorly understood. We sought to identify genetic loci associated with atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular accessory pathways or atrioventricular reciprocating tachycardia (AVAPs/AVRT)., Methods: We performed multiancestry meta-analyses of genome-wide association studies to identify genetic loci for AVNRT (4 studies) and AVAP/AVRT (7 studies). We assessed evidence supporting the potential causal effects of candidate genes by analyzing relations between associated variants and cardiac gene expression, performing transcriptome-wide analyses, and examining prior genome-wide association studies., Results: Analyses comprised 2384 AVNRT cases and 106 489 referents, and 2811 AVAP/AVRT cases and 1,483 093 referents. We identified 2 significant loci for AVNRT, which implicate NKX2-5 and TTN as disease susceptibility genes. A transcriptome-wide association analysis supported an association between reduced predicted cardiac expression of NKX2-5 and AVNRT. We identified 3 significant loci for AVAP/AVRT, which implicate SCN5A , SCN10A , and TTN/CCDC141 . Variant associations at several loci have been previously reported for cardiac phenotypes, including atrial fibrillation, stroke, Brugada syndrome, and electrocardiographic intervals., Conclusions: Our findings highlight gene regions associated with ion channel function (AVAP/AVRT), as well as cardiac development and the sarcomere (AVAP/AVRT and AVNRT) as important potential effectors of supraventricular tachycardia susceptibility., Competing Interests: Disclosures Dr Lubitz is a full-time employee of Novartis as of July 2022. Previously, Dr Lubitz received research support from Bristol Myers Squibb/Pfizer, Bayer AG, Boehringer Ingelheim, Fitbit, IBM, Medtronic, and Premier, Inc, and consulted for Bristol Myers Squibb/Pfizer, Bayer AG, Blackstone Life Sciences, and Invitae. Dr Ellinor receives research support from Bayer AG, IBM, and Bristol Myers Squibb/Pfizer and has consulted for Novartis, MyoKardia, and Bayer AG. Dr Damrauer receives research support for RenalytixAI and has consulted for Calico Labs. Dr Svendsen is a member of Medtronic advisory boards and has received speaker honoraria and research grants from Medtronic outside this work. Dr Cutler has consulted for Janssen Scientific. Dr Roselli is supported by a grant from Bayer AG to the Broad Institute focused on the development of therapeutics for cardiovascular disease. The other authors report no conflicts.

Background: Critically ill neonates receive care in the neonatal intensive care unit (NICU). Unfortunately, some neonates pass away in the NICU. Providing comprehensive neonatal palliative care and hospice services is crucial in supporting parents through the loss of their offspring. In our NICU, we identified that only 74.5% of nurses are able to properly recognize the need for palliative care and only 55% are able to implement the necessary procedures., Purpose: A project was designed and implemented to enhance the ability of nursing staff to recognize the need for and properly implement palliative care to improve the quality of this care in the NICU., Resolutions: We organized an on-the-job education and training program within our NICU with the goals of heightening awareness among nursing staff. In addition, a specialist palliative care operation flow chart, process preparation checklist, and palliative-care-related tools were created to facilitate the care process., Results: After program implementation, among nursing staff in our NICU, the palliative care recognition accuracy rate rose to 100% (from 74.5%) and the implementation rate rose to 94.8% (from 55%). The quality of provided neonatal palliative care and hospice services was significantly improved., Conclusions: The developed program was shown to significantly improve nursing staff recognition and implementation of neonatal palliative care in our NICU. This experience provides a reference for improving palliative care quality and for helping families effectively manage end-of-life challenges.

MEK inhibitors have immunomodulatory activity and potential for synergistic activity when combined with PD-1 inhibitors. We evaluated selumetinib (inhibitor of MEK1/2) plus pembrolizumab (anti‒PD-1 antibody) in patients with advanced/metastatic solid tumors. In this phase 1b study, adults with previously treated advanced/metastatic solid tumors received pembrolizumab 200 mg intravenously every 3 weeks plus selumetinib on days 1‒14 per 3-week cycle (2 weeks on/1 week off); selumetinib dosing began at 50 mg orally twice daily with escalation in 25 mg increments for ≤ 35 cycles. Primary endpoints were dose-limiting toxicities (DLTs), adverse events (AEs), and treatment discontinuations due to AEs. Thirty-two patients were enrolled. Dose escalation was completed up to selumetinib 125 mg twice daily. The target DLT rate of 30% was not reached at any dose level. In the selumetinib 100 mg group, 2/11 patients (18.2%) experienced DLTs (n = 1 grade 3 diarrhea, n = 1 grade 3 fatigue). In the selumetinib 125 mg group, 3/14 (21.4%) experienced DLTs (n = 1 grade 2 retinal detachment, n = 1 grade 3 retinopathy, n = 1 grade 3 stomatitis). Dose-related changes in pharmacokinetic exposures were observed for selumetinib and N-desmethyl selumetinib up to 100 mg (saturation at 125 mg). Two patients achieved partial responses (1 each with selumetinib 75 mg and 125 mg) for an objective response rate of 6%. The study was stopped early because of insufficient efficacy. Although the target DLT rate was not reached at any dose level and no new safety signals were identified, selumetinib plus pembrolizumab had limited antitumor activity in this population. Trial registration: ClinicalTrials.gov , NCT03833427., (© 2024. Merck & Co., Inc., Rahway, NJ, USA and its affiliates and Maxime Chénard-Poirier, Aaron R. Hansen, Martin E. Gutierrez, Drew Rasco, Yan Xing, Manish R. Sharma.)

Aminoglycosides are commonly used antibiotics for treatment of gram-negative bacterial infections, however, they might act on inner ear, leading to hair-cell death and hearing loss. Currently, there is no targeted therapy for aminoglycoside ototoxicity, since the underlying mechanisms of aminoglycoside-induced hearing impairments are not fully defined. This study aimed to investigate whether the calcium channel blocker verapamil and changes in intracellular & extracellular calcium could ameliorate aminoglycoside-induced ototoxicity in zebrafish. The present findings showed that a significant decreased number of neuromasts in the lateral lines of zebrafish larvae at 5 days' post fertilization after neomycin (20 μM) and gentamicin (20 mg/mL) exposure, which was prevented by verapamil. Moreover, verapamil (10-100 μM) attenuated aminoglycoside-induced toxic response in different external calcium concentrations (33-3300 μM). The increasing extracellular calcium reduced hair cell loss from aminoglycoside exposure, while lower calcium facilitated hair cell death. In contrast, calcium channel activator Bay K8644 (20 μM) enhanced aminoglycoside-induced ototoxicity and reversed the protective action of higher external calcium on hair cell loss. However, neomycin-elicited hair cell death was not altered by caffeine, ryanodine receptor (RyR) agonist, and RyR antagonists, including thapsigargin, ryanodine, and ruthenium red. The uptake of neomycin into hair cells was attenuated by verapamil and under high external calcium concentration. Consistently, the production of reactive oxygen species (ROS) in neuromasts exposed to neomycin was also reduced by verapamil and high external calcium. Significantly, zebrafish larvae when exposed to neomycin exhibited decreased swimming distances in reaction to droplet stimulus when compared to the control group. Verapamil and elevated external calcium effectively protected the impaired swimming ability of zebrafish larvae induced by neomycin. These data imply that prevention of hair cell damage correlated with swimming behavior against aminoglycoside ototoxicity by verapamil and higher external calcium might be associated with inhibition of excessive ROS production and aminoglycoside uptake through cation channels. These findings indicate that calcium channel blocker and higher external calcium could be applied to protect aminoglycoside-induced listening impairments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)