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Aim: We report diverse phenotypic consequences of the delQKP-1507-1509 cardiac sodium channel mutation in three generations of a Chinese family.Methods and Results: Clinical and electrocardiographic (ECG), echocardiographic examination was followed by direct sequencing of SCN5A, KCNQ1, HERG, and LAMIN A/C to screen genomic DNA from blood samples. Of two mutation carriers, the proband was born with conduction disorders including second-degree atrioventricular (AV) block with prolonged QTc interval, additionally showing left anterior fascicular block (LAFB), incomplete right bundle-branch block (IRBBB), and intermittent third-degree AV block at 2 years, and clinical presentations of multiple syncope despite normal electroencephalograms at 8 years. Continuous ECG monitoring following presentation at 13 years revealed prolonged QTc and biphasic T-waves, multiple episodes of ventricular tachycardia, ventricular fibrillation, and torsades de pointes. Transthoracal echocardiography then revealed left ventricular dilatation and reduced systolic function. Another mutation carrier showed features of long QT syndrome type 3 (LQT3), LAFB, and dilated cardiomyopathy (DCM). Two additional subjects died suddenly at 13 and 33 years.Conclusion: This data compliments and expands the spectrum of phenotypes resulting from this known gain-of-function mutation, including not only LQT3, cardiac conduction defects, and sudden death but also DCM, hitherto associated with loss-of-function mutations, for the first time. [ABSTRACT FROM AUTHOR]

This study examined a new emotional writing paradigm, that is PDDP. PDDP instructs participants to write diary in first-person pronoun first, and then narrate the same event from a different perspective using second-person pronoun. Finally, the participants write it again with third-person pronoun from yet another perspective. These three narrations were to be written in a consecutive sequential order. Results demonstrated that diary writers indeed benefited from features of PDDP. It also showed that highly anxious people received most long-term therapeutic effect from PDDP. We argue that PDDP enacts the needed mechanism to balance psychological distance prolonging and self-disclosure making in emotional writing. [ABSTRACT FROM AUTHOR]

Objectives: This single-arm, open-label, single-center observational pilot study assessed the safety and efficacy of ultrahigh-frequency dorsal root ganglia (UHF-DRG) stimulation in patients with chronic leg pain with or without low back pain. Such high-frequency electrostimulation had not been conducted in the human central nervous system previously., Materials and Methods: The primary objective was to evaluate the safety of UHF-DRG stimulation (2 Hz pulses with 50 msec pulse-width and 500 kHz intrapulse sine waves, 5-min duration per stimulation) by identifying incident adverse events (AE) and severe adverse events (SAE) during the trial. The secondary objectives included assessment of pain reduction using a numerical rating score (NRS), presence of paraesthesia, and changes in four pain medications (weak opioids, anticonvulsants, antidepressants, and non-steroid-anti-inflammatory drugs). One DRG lead was implanted for one day then removed, and the patients received maximal three times of UHF stimulation in total., Results: The study focused on ten cases. Two of them did not complete the study due to difficulty of lead implantation. There was no SAE in this trial. Among the ten cases, AEs occurred in eight, three experienced injection-related local pain and one of them had a post-dural-puncture headache, others had symptoms un-related to implantation procedure or UHF stimulation. The average NRS was reduced from 6.4 ± 1.1 at baseline to 2.9 ± 1.1 on the second-day post-implantation, and it was striking that the NRS was maintained at 3.6 ± 2.8 until 2 days after lead removal. The results showed a trend of lower frequency in medication use for all types of analgesics., Conclusions: In this first-in-human pilot study, we discovered that intermittent pulsed UHF-DRG stimulations ameliorated chronic lower limb pain for an extended period in humans. Our finding opens up a new neuromodulatory concept and may initiate a novel paradigm for treating intractable pain., (© 2024 World Institute of Pain.)

Background: To evaluate the effects of artificial intelligence (AI)-assisted dental monitoring (DM) with and without health counseling on the treatment outcomes and oral health-related quality of life (OHRQoL) of patients with periodontitis., Methods: Patients with periodontitis were randomly assigned to either an AI group (AI group, n = 28), an AI and health counseling group (AIHC group, n = 27), or a control group (n = 27). All patients underwent nonsurgical periodontal treatment. Patients in the AI and AIHC groups underwent additional AI-assisted DM and AI-assisted DM with oral health counseling, respectively, for 6 months. Data on OHRQoL and periodontal measures were collected at baseline and follow-ups., Results: At 3 months of follow-up, the AI and AIHC groups exhibited a significantly greater reduction in probing pocket depth (mean diff: -0.5 and -0.7) and clinical attachment level (mean diff: -0.5 and -0.6) compared with the control group. At 6 months of follow-up, the AI and AIHC groups exhibited a significantly greater improvement in OHRQoL (mean diff: -4.5 and -4.7) compared with the control group. At 3-month follow-up, the AIHC group exhibited a greater improvement in plaque index (mean diff: -0.2) and OHRQoL (mean diff: -4.3) compared with the AI group., Conclusion: AI-assisted DM can be used to remind patients with periodontitis of their oral hygiene at home and effectively improve their periodontal measures and long-term OHRQoL., Plain Language Summary: Gum disease is a common problem, but new technology could help. In this study, researchers looked at how AI affects gum health and quality of life (QoL). The researchers divided participants into 3 groups. One group used an AI system to monitor their gums at home. Another used AI plus got health advice. The third did not use any special technology. After 3 and 6 months, the AI groups had healthier gums, with less deep pockets and better gum attachment, compared to the group without AI. The group that also got health advice saw even greater improvements, like cleaner teeth and a bigger boost to their QoL. This is exciting because gum disease is tricky to manage alone. The AI system seems to help by reminding people to care for their teeth and gums. With expert guidance, the AI becomes an even more powerful tool for improving long-term oral health and well-being. This study shows how new technologies like AI could transform how we approach common health problems. By providing personalized support, AI can empower people to better manage their own health, leading to better outcomes., (© 2024 American Academy of Periodontology.)

Background: One key population related to achieving the global goal of hepatitis C virus (HCV) elimination is people who inject drugs (PWID). By surveying opioid agonist treatment (OAT) programs nationwide in Taiwan, this study aimed to examine (1) the current status of HCV care cascade provision by OAT programs and (2) the opinions of the programs' directors on integrating the HCV care cascade into OAT programs., Methods: From September to November 2022, questionnaires were sent via administrative networks to case managers for information on daily operation and routine booking and to directors for information on the HCV care cascade of 185 OAT programs. The responses of the 125 OAT programs that provided information from both case managers and directors were included for subsequent analyses., Results: Among the 125 OAT programs, 91 (73 %) offered HCV antibody testing, and 69 (55 %) offered HCV treatment services. The provision of HCV antibody testing was associated with being general hospital- or psychiatric hospital-based and having more care team personnel, whereas the provision of HCV treatment was associated with being general hospital-based. However, on-site HCV treatment was found to be rarely offered, and the future willingness to do so remained low., Conclusion: Our survey revealed that the provision of HCV screening and treatment in OAT programs in Taiwan has substantial room for improvement. Increasing the number of care personnel for satellite-dispensing OAT programs is key to expanding the service for HCV screening, as more issues related to multidisciplinary medical resources are involved in the provision of HCV treatment. Our results point to some options that might help accomplish these goals., Competing Interests: Declaration of competing interest We declare that we have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pleural infection leading to empyema is a severe condition marked by accumulated infected fluid in the pleural space. Pneumonia with parapneumonic effusion is its most common precursor. The global incidence of pleural infections has increased significantly, with existing literature mainly focusing on bacterial empyema, leaving a gap in comparative analyses.A retrospective review was conducted on 561 cases of bacterial, tuberculous, and fungal empyema over a 10-year period. The study compared and analysed overall survival rates, 30-day mortality rates after surgery, and clinical characteristics.The three empyema groups displayed distinct clinical characteristics. Fungal empyema had the worst overall survival compared to bacterial and tuberculous empyema, which had similar survival rates based on 30-day and 2-year mortality. Fungal empyema, advanced age, and high Charlson Comorbidity Index (CCI) score were independent predictors of poor prognosis.Fungal empyema has the highest mortality rate post-decortication surgery. Advanced age and high CCI score are independent predictors of poor prognosis..

Objectives: Thoracoscopic sympathectomy is an effective treatment for palmar hyperhidrosis. However, compensatory hyperhidrosis occurs frequently as a postoperative complication of the procedure. The goal of this study was to elucidate the clinical significance of thoracoscopic sympathectomy using our surgical procedure., Methods: Consecutive 151 patients who underwent thoracoscopic sympathectomy for palmar hyperhidrosis were studied. In addition, to investigate patients' satisfaction and long-term quality of life, 111 patients were asked to complete a mailing questionnaire survey, and 84 responded (response rate of 75.7%)., Results: All of the 151 patients reported a reduction in palmar sweating during the immediate postoperative period. None of the patients had pneumothorax, hemothorax, Horner's syndrome, or worsening of bradycardia. Based on the questionnaire, the surgical success rate was 98.8%. None of the patients had a recurrence of palmar hyperhidrosis during the long-term postoperative period. However, compensatory hyperhidrosis was reported in 82 patients (97.6%). In total, 94.0% of patients had high levels of postoperative satisfaction., Conclusions: Thoracoscopic sympathectomy is an effective surgical treatment for palmar hyperhidrosis. By contrast, the careful preoperative explanation of compensatory hyperhidrosis is considered to be very important., (© 2024. The Author(s).)

Background: Video-assisted thoracic surgery decortication for phase 3 thoracic empyema is widely accepted, but its optimal timing has not been established. We aim to investigate and assess this timing, in terms of overall survival, for chronic empyema., Methods: Two hundred four patients with pneumonia-caused phase 3 empyema were treated with video-assisted thoracic surgery decortication over 10-years at Changhua Christian Hospital. The 90-day post-operative survival status was analyzed, and we compared the survivor group versus the non-survivor group. A receiver operating characteristic curve was used to identify the optimal decortication timing., Results: A comparison between survivors and non-survivors showed statistical differences among age (p=0.004), presence of cardiovascular disease (p=0.018), presence of end-stage renal disease (p=0.002), duration to surgery (p=0.013), length of intensive care unit stay (p=0.010), and overall length of hospital stay (p=0.015). ROC curve analysis determined the cut-off for video-assisted thoracic surgery decortication, based on optimal 90-day post-operative survival, to be 7.5 days after hospitalization; mortality increases threefold thereafter (14.2% vs 44.6%, p<0.001). Multivariate analysis revealed that age, end-stage renal disease, pleural effusion pH≦7.2 and duration to surgery >7.5 days negatively impacted 90-day post-operative survival., Conclusions: Patients receiving decortication surgery within 7.5 days of hospital admission had better overall survival., (© 2024. The Author(s).)

This study aims to evaluate the potential benefits of treating spinal cord injury (SCI) patients with acidic fibroblast growth factor (aFGF), a potent neurotrophic factor that preserves neuronal survival. The study involved 12 tetraplegic patients with American Spinal Injury Association Impairment Scale (AIS) Grade A SCI who were randomly assigned to receive either a recombinant human aFGF or a placebo every 4 weeks for three doses. Participants underwent comprehensive evaluations of medical, neurological, and functional parameters at baseline and every 4 weeks after the first dose until the 48th week. The first dose was administered directly to the injury site during surgery within 6 weeks of the SCI, while the subsequent two doses were administered via lumbar puncture with a 4-week interval. The results revealed promising beneficial effects of aFGF on AIS Grade A SCI patients. The study report highlights aFGF's potential to expedite motor recovery in complete SCI patients and significantly increase the probability of a 10-point improvement when compared to the placebo group (odds ratio = 6.06, p = 0.0004). Furthermore, aFGF treatment exhibited a significant reduction ( p < 0.01) in the incidence or exacerbation rate of myelomalacia, a known secondary complication following SCIs., (© The Author(s) 2024. Published by Mary Ann Liebert, Inc.)

Metastatic lung cancer is a highly prevalent cancer with a very low chance of long-term survival. Metastasis at secondary sites requires that cancer cells develop anoikis resistance to survive during circulation. High levels of bone sialoprotein (BSP), a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs), have been shown to promote the spread of lung cancer cells; however, the effects of BSP in anoikis resistance are largely unknown. In this study, we determined that BSP promotes anoikis resistance in lung cancer cells. BSP was also shown to promote the expression of E-cadherin and vimentin (epithelial-to-mesenchymal transition markers, which have been utilized as indicators of anoikis resistance). It appears that BSP facilitates MMP-14-dependent anoikis resistance by inhibiting the synthesis of miR-150-5p and activating the ERK signalling pathway. Knockdown of BSP expression was shown to block lung cancer metastasis by lowering anoikis resistance in vivo. These results indicate that BSP is a promising target to deal with anoikis resistance and metastasis in human lung cancers., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background & Problems: Joint replacement wound stitches are typically not removed until two weeks after the operation. Therefore, patients with joint replacement must be able to execute proper wound care after discharge from the hospital to reduce the risk of wound infection. Prior data from Chang Gung Memorial Hospital's orthopedics ward indicate only 69% of joint-replacement patients are able to perform wound care properly at home. Potential causes for this noted by patients include age-related forgetfulness, being unable to discern redness or swelling in the wound, and language comprehension difficulties (i.e., Taiwanese vs. Mandarin). Poor rates of wound care may also be attributable to incomplete wound care education by nursing staff and wound care education being provided without adequate practice on the day of patient discharge., Purpose: This project was implemented to improve the accuracy of wound self-care performed by patients after joint replacement surgery and to enhance their related knowledge and wound-care technical correctness., Resolution: A wound care education checklist, wound care cue cards, wound care video clips, wound condition red flag cue cards, and customized wound care pack were proposed and implemented., Results: The rate of accuracy of wound self-care performance increased from 69% pretest to 98% posttest, showing the intervention to have effectively improved post-discharge wound care quality., Conclusions: To effectively improve the post-discharge accuracy of wound self-care in patients with joint replacement, the consistency of post-surgery wound care education given by nursing staff to patients should be improved, patients should be reminded of wound assessment and care steps, and patients should be aware that wound abnormalities require an immediate return to the hospital for follow-up treatment.

Recent studies suggest a need for reliable biomarkers enhancing prognosis prediction and treatment strategies in cancer. Here, we performed a data analysis bearing on the expression of SCN3B, voltage-gated sodium channel (VGSC) β3 subunit, as a possible candidate for the development of a glioma biomarker for the first time. This extends our previous review article that mentioned the potential of SCN3B as a prognostic biomarker for glioma survival, further examining its association with existing indicators and immune responses. We utilized clinical and genomic data from multiple glioma cohorts. These include the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). We employed analytical techniques including time-dependent receiver operating characteristic (ROC) analysis, decision curves analysis (DCA), and correlation studies with immune checkpoint markers. Our findings indicate a differential SCN3B expression between glioma grades, and that this significantly correlates with patient survival, particularly in oligodendroglioma subtypes. The DCA curves suggested that the inclusion of SCN3B in the prognostic model would improve decision-making in these subtypes. Moreover, SCN3B expression positively correlated with the presence of key immune cells and negatively correlated with several immune checkpoint inhibitors. This suggests potential roles in modulating immune responses in glioma. Thus, SCN3B emerges as a promising potential prognostic biomarker for glioma, especially for oligodendroglioma. Its dual correlations with prognosis and immune regulation present a compelling case for further experimental and clinical investigations to establish its utility in enhancing glioma management strategies. These findings underscore the importance of integrating novel biomarkers with traditional prognostic models to refine treatment paradigms and improve patient outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

exo-6b 2 -Methyl-substituted pentabenzocorannulene (exo-PBC-Me) was synthesized by the palladium-catalyzed cyclization of 1,2,3-triaryl-1H-cyclopenta[l]phenanthrene. Its bowl-shaped geometry with an sp 3 carbon atom in the backbone and a methyl group located at the convex (exo) face was verified by X-ray crystallography. According to DFT calculations, the observed conformer is energetically more favorable than the endo one by 39.9 kcal/mol. Compared to the nitrogen-doped analogs with intact π-conjugated backbones (see the main text), exo-PBC-Me displayed a deeper bowl depth (avg. 1.93 Å), redshifted and broader absorption (250-620 nm) and emission (from 585 to more than 850 nm) bands and a smaller optical HOMO-LUMO gap (2.01 eV). exo-PBC-Me formed polar crystals where all bowl-in-bowl stacking with close π ⋅ ⋅ ⋅ π contacts is arranged unidirectionally, providing the potential for applications as organic semiconductors and pyroelectric materials. This unusual structural feature, molecular packing, and properties are most likely associated with the assistance of the methyl group and the sp 3 carbon atom in the backbone., (© 2024 Wiley-VCH GmbH.)

Competing Interests: All the authors declare no conflict of interest.

Despite docetaxel combined with cisplatin and 5-fluorouracil (TPF) being the established treatment for advanced nasopharyngeal carcinoma (NPC), there are patients who do not respond positively to this form of therapy. However, the mechanisms underlying this lack of benefit remain unclear. DCAF7 is identified as a chemoresistance gene attenuating the response to TPF therapy in NPC patients. DCAF7 promotes the cisplatin resistance and metastasis of NPC cells in vitro and in vivo. Mechanistically, DCAF7 serves as a scaffold protein that facilitates the interaction between USP10 and G3BP1, leading to the elimination of K48-linked ubiquitin moieties from Lys76 of G3BP1. This process helps prevent the degradation of G3BP1 via the ubiquitin‒proteasome pathway and promotes the formation of stress granule (SG)-like structures. Moreover, knockdown of G3BP1 successfully reversed the formation of SG-like structures and the oncogenic effects of DCAF7. Significantly, NPC patients with increased levels of DCAF7 showed a high risk of metastasis, and elevated DCAF7 levels are linked to an unfavorable prognosis. The study reveals DCAF7 as a crucial gene for cisplatin resistance and offers further understanding of how chemoresistance develops in NPC. The DCAF7-USP10-G3BP1 axis contains potential targets and biomarkers for NPC treatment., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: This study aimed to investigate the clinical efficacy of intra-articular injections of medical chitosan for treating knee osteoarthritis (KOA) and measure the lipid metabolism profiles of the synovial tissue., Methods: Sixty patients with KOA undergoing conservative treatment were recruited and randomized into two groups: one without pharmacological intervention (OA group) and the other receiving course-based intra-articular medical chitosan injections (CSI group). Quantitative lipidomic profile of synovial tissue was analyzed. Functional scores, including Kellgren-Lawrence rating (K-L), Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scoring, and American Knee Society (AKS) scoring were conducted., Results: Survival from the initial conservative treatment to final knee arthroplasty was significantly longer in the CSI group compared to the OA group. Except for the presurgery VAS score, no statistically significant differences were observed in the other scores, including K-L, initial VAS, WOMAC, and AKS. However, the CSI group experienced more reductions in AKS-Knee subscores compared to the OA group. Compared to the CSI group, the OA group exhibited a significant upregulation in most differential lipids, particularly triacylglycerides (TAGs, 77%). The OA group had notably higher levels of long-chain unsaturated fatty acids., Conclusion: Intra-articular injection of medical chitosan significantly prolongs the survival period before knee arthroplasty and reduces the deposition of TAGs metabolites., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Lung cancer stands as the primary cause of cancer-related death across the globe. The standard therapeutic approach for lung cancer involves concurrent chemoradiotherapy, with consideration of prophylactic cranial irradiation for younger or well-performing patients. In this study, we aimed to investigate prognostic factors and the impacts of different treatment methods on overall survival for stage IIIA small cell lung cancer in Taiwan. We obtained data from the Taiwan Cancer Registry, which included clinical and pathology data of 579 stage IIIA small cell lung cancer patients from January 2010 to December 2018, for this retrospective study. The enrolled patients had data on age, sex, Charlson Comorbidity Index score, histologic grading, clinical T, clinical N, clinical stage, treatment modality, and overall survival time. We compared overall survival among different subgroups to assess the impacts of these prognostic factors. The five-year survival rate for all patients was 20.57%, with a median survival time of 15.79 months. The data suggest that Charlson Comorbidity Index score, histologic grade, and clinical stage subgroups did not reach statistically significant differences. During the multivariate analysis, age over 70 years, sex, and treatment method were determined to be statistically significant independent prognostic factors. Patients who underwent surgical intervention exhibited significantly better outcomes compared to those who did not undergo operation.. In conclusion, stage IIIA small cell lung cancer is a highly heterogeneous disease. Operation should be considered as one of the alternative treatments in stage IIIA Small cell lung cancer patients., Competing Interests: NO authors have competing interests, (Copyright: © 2024 Yu 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.)

Background: Purpose: High-flow nasal cannula (HFNC) has many benefits in various clinical conditions. The original hypothesis suggests that the high and constant fraction of inspired oxygen (FiO 2 ) is one of the main physiological effects. However, increasing evidence shows that there is a gap between the actual FiO 2 and administered FiO 2 . We aimed to determine the actual FiO 2 under different respiratory conditions and develop a regression model using a spontaneous breathing lung model., Methods: A spontaneous breathing simulation model was built using an airway manikin and a model lung. The FiO 2 was measured under different respiratory conditions with varying tidal volumes and respiratory and HFNC flow rates. The relationships between the respiratory parameters and actual FiO 2 were determined and used to build the predictive model., Results: The actual FiO 2 was negatively correlated with respiratory rate and tidal volume and positively correlated with HFNC flow. The regression model could not be developed using simple respiratory parameters. Therefore, we introduced a new variable, defined as flow ratio, which equaled the HFNC flow divided by inspiratory flow. Our equation demonstrated that the actual FiO 2 was mainly determined by the flow ratio in a non-linear relationship. Accordingly, a flow ratio greater than 1 did not ensure a constant high FiO 2 , whereas a flow ratio >1.435 could produce FiO 2 >0.9., Conclusion: The FiO 2 during HFNC was not constant even at sufficiently high oxygen flow compared with inspiratory flow. The predictive model showed that the actual FiO 2 was mainly determined by the flow ratio., 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 © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Solid tumours have abnormally high intracellular [Na + ]. The activity of various Na + channels may underlie this Na + accumulation. Voltage-gated Na + channels (VGSCs) have been shown to be functionally active in cancer cell lines, where they promote invasion. However, the mechanisms involved, and clinical relevance, are incompletely understood. Here, we show that protein expression of the Na v 1.5 VGSC subtype strongly correlates with increased metastasis and shortened cancer-specific survival in breast cancer patients. In addition, VGSCs are functionally active in patient-derived breast tumour cells, cell lines, and cancer-associated fibroblasts. Knockdown of Na v 1.5 in a mouse model of breast cancer suppresses expression of invasion-regulating genes. Na v 1.5 activity increases ATP demand and glycolysis in breast cancer cells, likely by upregulating activity of the Na + /K + ATPase, thus promoting H + production and extracellular acidification. The pH of murine xenograft tumours is lower at the periphery than in the core, in regions of higher proliferation and lower apoptosis. In turn, acidic extracellular pH elevates persistent Na + influx through Na v 1.5 into breast cancer cells. Together, these findings show positive feedback between extracellular acidification and the movement of Na + into cancer cells which can facilitate invasion. These results highlight the clinical significance of Na v 1.5 activity as a potentiator of breast cancer metastasis and provide further evidence supporting the use of VGSC inhibitors in cancer treatment., (© 2024. The Author(s).)

The utility of a universal DNA 'barcode' fragment (658 base pairs of the Cytochrome C Oxidase I [COI] gene) has been established as a useful tool for species identification, and widely criticized as one for understanding the evolutionary history of a group. Large amounts of COI sequence data have been produced that hold promise for rapid species identification, for example, for biosecurity. The fruit fly tribe Dacini holds about a thousand species, of which 80 are pests of economic concern. We generated a COI reference library for 265 species of Dacini containing 5601 sequences that span most of the COI gene using circular consensus sequencing. We compared distance metrics versus monophyly assessments for species identification and although we found a 'soft' barcode gap around 2% pairwise distance, the exceptions to this rule dictate that a monophyly assessment is the only reliable method for species identification. We found that all fragments regularly used for Dacini fruit fly identification >450 base pairs long provide similar resolution. 11.3% of the species in our dataset were non-monophyletic in a COI tree, which is mostly due to species complexes. We conclude with recommendations for the future generation and use of COI libraries. We revise the generic assignment of Dacus transversus stat. rev. Hardy 1982, and Dacus perpusillus stat. rev. Drew 1971 and we establish Dacus maculipterus White 1998 syn. nov. as a junior synonym of Dacus satanas Liang et al. 1993., (© 2024 John Wiley & Sons Ltd.)

Voltage-gated sodium channels (VGSCs) initiate action potentials in electrically excitable cells and tissues. Surprisingly, some VGSC genes are aberrantly expressed in a variety of cancers, derived from "non-excitable" tissues that do not generate classic action potentials, showing potential as a promising pharmacological target for cancer. Most of the previous review articles on this topic are limited in scope, and largely unable to provide researchers with a comprehensive understanding of the role of VGSC in cancers. Here, we review the expression patterns of all nine VGSC α-subunit genes (SCN1A-11A) and their four regulatory β-subunit genes (SCN1B-4B). We reviewed data from the Cancer Genome Atlas (TCGA) database, complemented by an extensive search of the published papers. We summarized and reviewed previous independent studies and analyzed the VGSC genes in the TCGA database regarding the potential impact of VGSC on cancers. A comparison between evidence gathered from independent studies and data review was performed to scrutinize potential biases in prior research and provide insights into future research directions. The review supports the view that VGSCs play an important role in diagnostics as well as therapeutics of some cancer types, such as breast, colon, prostate, and lung cancer. This paper provides an overview of the current knowledge on voltage-gated sodium channels in cancer, as well as potential avenues for further research. While further research is required to fully understand the role of VGSCs in cancer, the potential of VGSCs for clinical diagnosis and treatment is promising., (© 2024. The Author(s).)

This study aims to explore the efficacy of group music and game therapy in enhancing the well-being of the institutionalised elderly. The implementation of group music and game therapy have significantly improved the well-being of the participating elderly residents in Long-Term Care Facilities. These participants demonstrated increased engagement and achieved interpersonal interaction objectives during the sessions.

Objective: The aim of the study was to explore the psychological characteristics of the individuals with various suicide risks using computerized text analysis, in the hopes of a better understanding of suicide trajectories., Methods: 627 first-time callers' records were randomly selected from Taiwan An-Shin Hotline database between 2013 and 2018. The voice records were evaluated by two psychologists to determine the levels of suicide risk (156 with uncertainty of risk, 177 with low suicidal ideation, 157 with high suicidal ideation, and 137 with suicide preparation/attempt) and transcribed into text. The Linguistic Inquiry and Word Count 2015 (LIWC2015) program combined with Chinese dictionary were then used to calculate the frequency of word categories., Results: Exploratory factor analysis identified four mindsets of language characteristics, named "opposition and questioning", "active engagement", "negative rumination", and "focus on death". Psychological descriptions of the mindsets were also obtained through correlation analysis with the LIWC2015 categories and indicators. The four mindsets effectively distinguished the callers with different levels of suicide risk., Conclusion: The psychological characteristics of people with various suicide risks can be described and differentiated via the closed-word categories and composite indicators. These results provide useful information for practitioners and researchers., (© 2024 American Association of Suicidology.)

We explored physiological effects of the sodium-glucose co-transporter-2 inhibitor empagliflozin on intact experimentally hypertrophic murine hearts following transverse aortic constriction (TAC). Postoperative drug (2-6 weeks) challenge resulted in reduced late Na + currents, and increased phosphorylated (p-)CaMK-II and Nav1.5 but not total (t)-CaMK-II, and Na + /Ca 2+ exchanger expression, confirming previous cardiomyocyte-level reports. It rescued TAC-induced reductions in echocardiographic ejection fraction and fractional shortening, and diastolic anterior and posterior wall thickening. Dual voltage- and Ca 2+ -optical mapping of Langendorff-perfused hearts demonstrated that empagliflozin rescued TAC-induced increases in action potential durations at 80% recovery (APD 80 ), Ca 2+ transient peak signals and durations at 80% recovery (CaTD 80 ), times to peak Ca 2+ (TTP 100 ) and Ca 2+ decay constants (Decay 30-90 ) during regular 10-Hz stimulation, and Ca 2+ transient alternans with shortening cycle length. Isoproterenol shortened APD 80 in sham-operated and TAC-only hearts, shortening CaTD 80 and Decay 30-90 but sparing TTP 100 and Ca 2+ transient alternans in all groups. All groups showed similar APD 80 , and TAC-only hearts showed greater CaTD 80 , heterogeneities following isoproterenol challenge. Empagliflozin abolished or reduced ventricular tachycardia and premature ventricular contractions and associated re-entrant conduction patterns, in isoproterenol-challenged TAC-operated hearts following successive burst pacing episodes. Empagliflozin thus rescues TAC-induced ventricular hypertrophy and systolic functional, Ca 2+ homeostatic, and pro-arrhythmogenic changes in intact hearts., (© 2024. The Author(s).)

Background/purpose: Additive manufacturing (AM) technology, such as selective laser melting (SLM), has been used to fabricate medical devices of Ti-6wt.% Al-4wt.%V (Ti6Al4V) alloys in dentistry. Strontium (Sr) has been shown to have the potential to treat osteoporosis. The aim of this study was to investigate the physicochemical and biological properties of strontium-containing coatings on selective laser melted Ti6Al4V (SLM-Ti6Al4V) substrate., Materials and Methods: The disk of Ti6Al4V was prepared by SLM method. The strontium-containing coatings were prepared by micro-arc oxidation (MAO) in aqueous electrolytes. The surface topography, chemical composition, and phase of strontium-containing MAO (SrMAO) coatings were performed by scanning electron microscope (SEM), energy dispersive X-ray spectrometer (EDS), and thin film X-ray diffraction (TF-XRD), respectively. The apatite-forming ability of the MAO coatings was conducted in simulating body fluid (SBF), and the cell proliferation was determined by methylthiazoletetrazolium (MTT) assay., Results: The microstructure of SLM-Ti6Al4V displays acicular α-phase organization. The TF-XRD results indicated that the phase of SrMAO coating was anatase, rutile, and titanium. The calcium, phosphorus, and strontium were detected in the coatings by EDS. Using the SEM, the surface morphology of SrMAO coatings exhibited a uniform 3D porous structure. The SrMAO coatings could induce a bone-like apatite layer after immersion in SBF, and presented significantly higher cell proliferation than untreated specimens in in-vitro experiments., Conclusion: All findings in this study indicate that SrMAO coatings formed on SLM-Ti6Al4V surfaces exhibit a benefit on biological responses and thereby are suitable for biomedical applications., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Both concurrent chemoradiotherapy (CCRT) and induction chemotherapy (ICT) followed by CCRT are standard care of advanced nasopharyngeal carcinoma (NPC). However, tailoring personalized treatment is lacking. Herein, we established a radiogenomic clinical decision support system to classify patients into three subgroups according to their predicted disease-free survival (DFS) with CCRT and ICT response. The CCRT-preferred group was suitable for CCRT since they achieved good survival with CCRT, which could not be improved by ICT. The ICT-preferred group was suitable for ICT plus CCRT since they had poor survival with CCRT; additional ICT could afford an improved DFS. The clinical trial-preferred group was suitable for clinical trials since they exhibited poor survival regardless of receiving CCRT or ICT plus CCRT. These findings suggest that our radiogenomic clinical decision support system could identify optimal candidates for CCRT, ICT plus CCRT, and clinical trials, and may thus aid in personalized management of advanced NPC., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: Whole plant senescence represents the final stage in the life cycle of annual plants, characterized by the decomposition of aging organs and transfer of nutrients to seeds, thereby ensuring the survival of next generation. However, the transcriptomic profile of vegetative organs during this death process remains to be fully elucidated, especially regarding the distinctions between natural programmed death and artificial sudden death induced by herbicide., Results: Differential genes expression analysis using RNA-seq in leaves and roots of Arabidopsis thaliana revealed that natural senescence commenced in leaves at 45-52 days after planting, followed by roots initiated at 52-60 days. Additionally, both organs exhibited similarities with artificially induced senescence by glyphosate. Transcription factors Rap2.6L and WKRY75 appeared to serve as central mediators of regulatory changes during natural senescence, as indicated by co-expression networks. Furthermore, the upregulation of RRTF1, exclusively observed during natural death, suggested its role as a regulator of jasmonic acid and reactive oxygen species (ROS) responses, potentially triggering nitrogen recycling in leaves, such as the glutamate dehydrogenase (GDH) shunt. Root senescence was characterized by the activation of AMT2;1 and GLN1;3, facilitating ammonium availability for root-to-shoot translocation, likely under the regulation of PDF2.1., Conclusions: Our study offers valuable insights into the transcriptomic interplay between phytohormones and ROS during whole plant senescence. We observed distinct regulatory networks governing nitrogen utilization in leaf and root senescence processes. Furthermore, the efficient allocation of energy from vegetative organs to seeds emerges as a critical determinant of population sustainability of annual Arabidopsis., (© 2024. The Author(s).)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We previously reported comparable 3-year regional relapse-free survival (RRFS) using elective upper-neck irradiation (UNI) in N0-1 nasopharyngeal carcinoma (NPC) compared with standard whole-neck irradiation (WNI). Here, we present the prespecified 5-year overall survival (OS), RRFS, late toxicity, and additional analyses. In this randomized trial, patients received UNI (n = 224) or WNI (n = 222) for an uninvolved neck. After a median follow-up of 74 months, the UNI and WNI groups had similar 5-year OS (95.9% v 93.1%, hazard ratio [HR], 0.63 [95% CI, 0.30 to 1.35]; P = .24) and RRFS (95.0% v 94.9%, HR, 0.96 [95% CI, 0.43 to 2.13]; P = .91) rates. The 5-year disease-free survivors in the UNI group had a lower frequency of hypothyroidism (34% v 48%; P = .004), neck tissue damage (29% v 46%; P < .001), dysphagia (14% v 27%; P = .002), and lower-neck common carotid artery stenosis (15% v 26%; P = .043). The UNI group had higher postradiotherapy circulating lymphocyte counts than the WNI group (median: 400 cells/μL v 335 cells/μL, P = .007). In conclusion, these updated data confirmed that UNI of the uninvolved neck is a standard of care in N0-1 NPC, providing outstanding efficacy and reduced long-term toxicity, and might retain more immune function.

Aurora kinase inhibitors, such as alisertib, can destabilize MYC-family oncoproteins and have demonstrated compelling antitumor efficacy. In this study, we report 6K465, a novel pyrimidine-based Aurora A inhibitor, that reduces levels of c-MYC and N-MYC oncoproteins more potently than alisertib. In an analysis of the antiproliferative effect of 6K465, the sensitivities of small cell lung cancer (SCLC) and breast cancer cell lines to 6K465 were strongly associated with the protein levels of c-MYC and/or N-MYC. We also report DBPR728, an acyl-based prodrug of 6K465 bearing fewer hydrogen-bond donors, that exhibited 10-fold improved oral bioavailability. DBPR728 induced durable tumor regression of c-MYC- and/or N-MYC-overexpressing xenografts including SCLC, triple-negative breast cancer, hepatocellular carcinoma, and medulloblastoma using a 5-on-2-off or once-a-week dosing regimen on a 21-day cycle. A single oral dose of DBPR728 at 300 mg/kg induced c-MYC reduction and cell apoptosis in the tumor xenografts for more than 7 days. The inhibitory effect of DBPR728 at a reduced dosing frequency was attributed to its uniquely high tumor/plasma ratio (3.6-fold within 7 days) and the long tumor half-life of active moiety 6K465. Furthermore, DBPR728 was found to synergize with the mTOR inhibitor everolimus to suppress c-MYC- or N-MYC-driven SCLC. Collectively, these results suggest DBPR728 has the potential to treat cancers overexpressing c-MYC and/or N-MYC., (©2024 American Association for Cancer Research.)

Lung cancer stands as a major contributor to cancer-related fatalities globally, with cigarette smoke playing a pivotal role in its development and metastasis. Cigarette smoke is also recognized as a risk factor for bone loss disorders like osteoporosis. However, the association between cigarette smoke and another bone loss disorder, lung cancer osteolytic bone metastasis, remains largely uncertain. Our Gene Set Enrichment Analysis (GSEA) indicated that smokers among lung cancer patients exhibited higher expression levels of bone turnover gene sets. Both The Cancer Genome Atlas (TCGA) database and our clinic samples demonstrated elevated expression of the osteolytic factor IL-6 in ever-smokers with bone metastasis among lung cancer patients. Our cellular experiments revealed that benzo[α]pyrene (B[α]P) and cigarette smoke extract (CSE) promoted IL-6 production and cell migration in lung cancer. Activation of the PI3K, Akt, and NF-κB signaling pathways was involved in cigarette smoke-augmented IL-6-dependent migration. Additionally, cigarette smoke lung cancer-secreted IL-6 promoted osteoclast formation. Importantly, blocking IL-6 abolished cigarette smoke-facilitated lung cancer osteolytic bone metastasis in vivo . Our findings provide evidence that cigarette smoke is a risk factor for osteolytic bone metastasis. Thus, inhibiting IL-6 may be a valuable therapeutic strategy for managing osteolytic bone metastasis in lung cancer patients who smoke., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Renal tubules are featured with copious mitochondria and robust transport activity. Mutations in mitochondrial genes cause congenital renal tubulopathies, and changes in transport activity affect mitochondrial morphology, suggesting mitochondrial function and transport activity are tightly coupled. Current methods of using bulk kidney tissues or cultured cells to study mitochondrial bioenergetics are limited. Here, we optimized an extracellular flux analysis (EFA) to study mitochondrial respiration and energy metabolism using microdissected mouse renal tubule segments. EFA detects mitochondrial respiration and glycolysis by measuring oxygen consumption and extracellular acidification rates, respectively. We show that both measurements positively correlate with sample sizes of a few centimeter-length renal tubules. The thick ascending limbs (TALs) and distal convoluted tubules (DCTs) critically utilize glucose/pyruvate as energy substrates, whereas proximal tubules (PTs) are significantly much less so. Acute inhibition of TALs' transport activity by ouabain treatment reduces basal and ATP-linked mitochondrial respiration. Chronic inhibition of transport activity by 2-week furosemide treatment or deletion of with-no-lysine kinase 4 (Wnk4) decreases maximal mitochondrial capacity. In addition, chronic inhibition downregulates mitochondrial DNA mass and mitochondrial length/density in TALs and DCTs. Conversely, gain-of-function Wnk4 mutation increases maximal mitochondrial capacity and mitochondrial length/density without increasing mitochondrial DNA mass. In conclusion, EFA is a sensitive and reliable method to investigate mitochondrial functions in isolated renal tubules. Transport activity tightly regulates mitochondrial bioenergetics and biogenesis to meet the energy demand in renal tubules. The system allows future investigation into whether and how mitochondria contribute to tubular remodeling adapted to changes in transport activity., (© 2024 Federation of American Societies for Experimental Biology.)

Although many cohort studies have reported that long-term exposure to particulate matter (PM) causes lung cancer, the molecular mechanisms underlying the PM-induced increases in lung cancer progression remain unclear. We applied the lung cancer cell line A549 (Parental; A549.Par) to PM for an extended period to establish a mimic PM-exposed lung cancer cell line, A549.PM. Our results indicate that A549.PM exhibits higher cell growth and proliferation abilities compared to A549.Par cells in vitro and in vivo . The RNA sequencing analysis found amphiregulin (AREG) plays a critical role in PM-induced cell proliferation. We observed that PM increases AREG-dependent lung cancer proliferation through glutamine metabolism. In addition, the EGFR/PI3K/AKT/mTOR signaling pathway is involved in PM-induced solute carrier family A1 member 5 (SLC1A5) expression and glutamine metabolism. Our findings offer important insights into how lung cancer proliferation develops upon exposure to PM., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)