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Chieh-Min Liu,1 Bing-Shen Huang,2,3 Yi-Hao Yen,4 Yu-Ming Wang,1,5,6 Eng-Yen Huang,1,5,6 Hsuan-Chih Hsu,1 Tzu-Ting Huang,1 Yao-Hsu Yang,5,7,8 Jen-Yu Cheng1 1Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; 3Graduate Institute of Clinical Medicine, Chang Gung University, Taoyuan, Taiwan; 4Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 5School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan; 6Department of Radiation Oncology, Xiamen Chang Gung Hospital, Fujian, People’s Republic of China; 7Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; 8Health Information and Epidemiology Laboratory of Chang Gung Memorial Hospital, Chiayi, TaiwanCorrespondence: Jen-Yu ChengDepartment of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, TaiwanTel +886-9-10722590Email york480@cgmh.org.twPurpose: Evidence is lacking concerning the benefit of the combination of sorafenib and radiotherapy to treat advanced hepatocellular carcinoma (HCC). To date, no publication has reported the outcomes of radiotherapy alone versus concurrent therapy. We aimed to compare the effectiveness of radiotherapy alone versus concurrent radiotherapy and sorafenib for locally advanced hepatocellular carcinoma.Materials and Methods: We conducted a propensity score matching (PSM) cohort study comparing the effectiveness of the concurrent use of sorafenib and external beam radiotherapy versus radiotherapy alone in Barcelona Clinic Liver Cancer (BCLC) stage B or C, nonsurgically managed, nonmetastatic patients with HCC. Two subpopulations were matched based on baseline characteristics. Stratified analysis was also performed to assess the heterogeneous effects of the two arms. Overall survival (OS) was compared. Radiation-induced liver disease (RILD) and overt gastrointestinal (GI) bleeding events were also recorded.Results: Seven hundred thirty-one BCLC stage B or C nonmetastatic HCC patients were identified from 2007 to 2017. Of these, 347 patients met the inclusion criteria (Radiotherapy alone: 269 patients; concurrent therapy: 78 patients). Propensity score matching yielded 73 patients each in the radiotherapy and concurrent groups. The median OS was 9.6 months in the radiotherapy-alone group and 9.9 months in the concurrent group (hazard ratio (HR): 1.12; 95% CI=0.78– 1.62; p=0.544). Posttreatment toxicities, including radiation-induced liver disease and overt gastrointestinal bleeding, showed no significant differences between the groups.Conclusion: In our study, the concurrent use of sorafenib and conventional external beam radiotherapy shows no survival benefit over radiotherapy alone for locally advanced hepatocellular carcinoma.Keywords: radiotherapy, sorafenib, hepatocellular carcinoma

Chunyu Zhang,1 Jiaoying Cheng,2 Yan Jiang,3 Junyang Liu41Department of Health Reform and Development, China–Japan Friendship Hospital, Beijing, People’s Republic of China; 2Department of Obstetrics and Gynecology, China–Japan Friendship Hospital, Beijing, People’s Republic of China; 3National Management Center of 12320 Health Hotline, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 4Department of Pharmacy, China–Japan Friendship Hospital, Beijing, People’s Republic of ChinaAbstract: Fungal infection has increased in the past 2 decades in China. There are three classes of antifungal drugs, polyenes, azoles, and echinocandins, that are applied frequently in China. Caspofungin, which disrupts the fungal cell wall glucan formation through inhibiting the enzyme 1,3-ß-glucan synthase, is one of the echinocandins. According to the results of clinical practices applied in China, caspofungin has shown to be superior to the other two classes of antifungal drugs, due to its efficacy in treating fungal infection (15% superior to fluconazole); fewer adverse events such as infusion-related reaction, hepatic dysfunction, and vomiting (25%–50% lower incidence rate); rapid resolution of symptoms (about 3 days quicker than amphotericin B); and absence of antagonism in combination with other antifungal drugs. However, caspofungin will remain as a second-line antifungal drug in the near future because of its high price and the policy of health insurance reimbursement in China.Keywords: fungal infection, caspofungin, efficacy, adverse event

Due to the improvement of the signal processing and image technology, the clinical ultrasound system becomes an important tool to assist doctors in detecting diseases. Hence, it is necessary to know the biological effects of ultrasound in human tissue. In ultrasonic waves, the discrepancy between classic elasticity and experimental elasticity becomes a particularly important problem, especially when there are higher frequencies and smaller wavelengths, i.e., in the case of wave propagation in human muscle and compact bone. Consequently, the influence of the microstructure is important and this fact leads to the generation of new types of waves unknown in classic elasticity. General continuum theories, such as couple stress theory and micropolar theory, have degrees of freedom in addition to those of classic elasticity. Such theories are thought to be applicable to composites with granular or porous structure, effective chiral composite, and human compact bone. In this work, a theoretical analysis concerning the reflected and transmitted fields of an incident plane wave P propagating at the human muscle-compact bone interface has been investigated. The results show that the wave fields are affected by microstructures of the human bone. Knowledge of this occurrence may offer some contribution to the understanding of the ultrasound propagation in the biological effects of human tissue.

Objectives: The Phase 3 Study 338 (NCT02834793) assessed long-term clinical outcomes of adjunctive perampanel in patients ≥2 years of age with uncontrolled seizures associated with Lennox-Gastaut syndrome (LGS)., Methods: Eligible patients were diagnosed with LGS and receiving one to four concomitant antiseizure medications with an average of two or more drop seizures/week during baseline. The study comprised an 18-week double-blind, randomized, placebo-controlled Core Study and ≥52-week open-label Extension. The primary endpoint was median percent change in drop seizure frequency per 28 days during the Core Study. Key secondary endpoints included responder rates, seizure-freedom rates, and safety outcomes. Post hoc analyses were performed encompassing a broader range of drop seizures or all countable motor seizures., Results: Seventy patients were randomized into the Core Study (perampanel, n = 34; placebo, n = 36), and 58 entered the Extension. In the Core Study, numerically greater median percent reductions in drop seizure frequency were observed with perampanel (23.1%) vs placebo (4.5%) using prespecified assessments (p = .107), whereas significantly greater reductions were detected using the broader definition (48.6% vs -.7%, respectively, p = .001) or all countable motor seizures (44.0% vs -.6%, respectively, p = .017). The 50% responder rate for drop seizures was higher with perampanel vs placebo using modern definitions. Reductions in seizure frequency with perampanel were maintained over 52 weeks. Treatment-emergent adverse events occurred in 85.3% of perampanel-treated patients (somnolence [23.5%] was the most frequent) and 72.2% of placebo-treated patients., Significance: This study had a reduced sample size and was underpowered. Although the difference in reductions in drop seizure frequency between treatments was not statistically significant by prespecified assessments, adjunctive perampanel demonstrated sustained efficacy in reducing drop seizures associated with LGS for ≤71 weeks using modern definitions. No new safety signals emerged. These observations suggest the long-term efficacy and safety of perampanel in the LGS population., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: E2730, an uncompetitive γ-aminobutyric acid (GABA) transporter-1 (GAT-1) inhibitor, has potent anti-seizure effects in a rodent model of chronic temporal lobe epilepsy, the kainic acid status epilepticus (KASE) rat model. In this study, we examined purported neuroimaging and physiological surrogate biomarkers of the effect of E2730 on brain GABAergic function., Methods: We conducted a randomized cross-over study, incorporating 1-week treatments with E2730 (100 mg/kg/day subcutaneous infusion) or vehicle in epileptic post-KASE rats. KASE rats underwent serial 9.4 T magnetic resonance spectroscopy (MRS) measuring GABA and other brain metabolites, [ 18 F]Flumazenil positron emission tomography (PET) quantifying GABA A receptor availability, quantitative electroencephalography (qEEG) and transcranial magnetic stimulation (TMS)-mediated motor activity, as well as continuous video-EEG recording to measure spontaneous seizures during each treatment. Age-matched, healthy control animals treated with E2730 or vehicle were also studied., Results: E2730 treatment significantly reduced spontaneous seizures, with 8 of 11 animals becoming seizure-free. MRS revealed that E2730-treated animals had significantly reduced taurine levels. [ 18 F]Flumazenil PET imaging revealed no changes in GABA receptor affinity or density during E2730 treatment. The power of gamma frequency oscillations in the EEG was decreased significantly in the auditory cortex and hippocampus of KASE and control rats during E2730 treatment. Auditory evoked gamma frequency power was enhanced by E2730 treatment in the auditory cortex of KASE and healthy controls, but only in the hippocampus of KASE rats. E2730 did not influence motor evoked potentials triggered by TMS., Significance: This study identified clinically relevant changes in multimodality imaging and functional purported biomarkers of GABAergic activity during E2730 treatment in epileptic and healthy control animals. These biomarkers could be utilized in clinical trials of E2730 and potentially other GABAergic drugs to provide surrogate endpoints, thereby reducing the cost of such trials., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Purpose: Investigate risk factors for short-term reactivation of retinopathy of prematurity (ROP) after intravitreal ranibizumab (IVR) therapy and determine safety and efficacy of repeat injections., Methods: Retrospective chart review study of patients screened for ROP as inpatients between 2013 and 2023 who received IVR within the UCLA health care system. Primary outcomes were rates and timing of short-term ROP reactivation, defined as repeat worsening of ROP to stage 2 or 3 before 52 weeks postmenstrual age, as well as risk factors for reactivation. Other outcomes included adverse events and rates of reactivation after a second intravitreal injection., Results: Eighty-two eyes of 43 patients received primary IVR 0.25 mg/0.025 cc for type 1 ROP. Thirteen patients (22 eyes) (30.2% of patients, 26.8% of eyes) developed short-term reactivation an average of 7.2 weeks ± 1.7 weeks after treatment. Increased reactivation risk was associated with zone I disease (odds ratio 6.23, 95% CI, 1.35-28.7, P = 0.019), lower postmenstrual age at first injection (odds ratio 1.64, 95% CI, 1.19-2.26; P = 0.003), and lower gestational age at birth (odds ratio 1.80, 95% CI, 1.04-3.13, P = 0.037). Of the 13 patients that received repeat injections, five required laser treatment for a second reactivation (11.6% of patients receiving IVR). No eyes developed retinal vascular occlusion, endophthalmitis, or cataract., Conclusion: Repeat injections may be required after primary IVR for aggressive ROP. Repeat IVR treatment for ROP is effective and poses few ophthalmic adverse events, although additional reactivation remains a risk.

Acacia confusa Merr. (Fabaceae) (A. confusa) is a native tree species of Taiwan, commonly found in the low-altitude mountains and hilly areas of the Hengchun Peninsula. This evergreen, perennial, and large-sized tree was the focus of a study that employed various chromatographic and spectroscopic methods to analyze the hot water extract of its flowers. The analysis revealed that the major components of the extract were myricitrin, quercitrin, europetin-3-O-rhamnoside, and chalconaringenin-2'-xyloside, with respective concentrations of approximately 0.22, 0.02, 0.26, and 0.10 mg/g of the flowers. Subsequent cell assays were conducted to assess the inhibitory effect of the extract on lipid synthesis in fat cells. Oil Red O staining results indicated that the extract significantly suppressed fatty acid accumulation in 3T3-L1 cells, with the most pronounced effect observed at a concentration of 180 μg/ml. Furthermore, the hot water extract of A. confusa flowers was found to increase the phosphorylation of AMP-activated protein kinase (AMPK), decrease the phosphorylation of cAMP response element-binding protein (CREB), and reduce the expression of glucocorticoid receptor (GR) protein. This, in turn, inhibited the expression of downstream transcription factors such as CCAT/ehancer binding proteins α (C/EBPα), CCAT/ehancer binding proteins β (C/EBPβ), CCAT/ehancer binding proteins δ (C/EBPδ), peroxisome proliferation-actived receptor γ (PPARγ), and sterol regulatory element binding proteins-1 (SREBP-1). Consequently, the expression of lipid synthesis-related proteins acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and fatty acid translocase (CD36) was reduced, ultimately inhibiting lipid generation. Therefore, the hot water extract of A. confusa flowers shows potential for development as a weight-loss tea., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Objectives: Horticultural therapy (HT) has garnered growing interest because of its psychological and physical benefits. Previous reviews have demonstrated its therapeutic effects in older adults with cognitive impairment or mental illnesses. However, its impact on older adults without dementia has not been synthesized. This systematic review studied the effects of HT on the physical and psychosocial functions of older adults without dementia., Design: Systematic review and meta-analysis., Settings and Participants: Older adults without dementia ≥60 years of age., Methods: Randomized controlled trials and quasi-experimental studies were systematically searched in 7 databases. The Cochrane Risk of Bias Tool version 2 and the Risk of Bias in Non-randomized Studies of Interventions tool were used to assess study quality. A random-effects meta-analysis with Hedges' g was conducted to estimate the effect size, and Cochran's Q test and I 2 were used to evaluate heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation approach was applied to determine the overall quality of evidence., Results: Twenty-seven studies, including 11 randomized controlled trials and 16 quasi-experimental studies comprising 1629 older adults from 11 countries, were included. HT tended to improve psychosocial outcomes in older adults, particularly in terms of self-efficacy (g = 0.52; 95% CI, 0.26-0.79) and self-esteem (g = 0.52; 95% CI, 0.26-0.79). In terms of physical benefits, HT appeared to have a greater impact on aerobic endurance, with a large effect size (g = 0.84; 95% CI, 0.54-1.15), compared to agility, which showed a smaller effect size (g = 0.45; 95% CI, -0.90 to -0.01)., Conclusions and Implications: This review demonstrated that HT could provide psychosocial and physical benefits to older adults without dementia. These benefits include slight improvements in self-efficacy, self-esteem, aerobic endurance, and agility. However, the certainty of this evidence is very low due to the quasi-experimental design and potential bias in outcome measurements. Further research with well-designed clinical trials is necessary to confirm its effectiveness., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Purpose: To report eight cases of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) or persistent placoid maculopathy (PPM) initially masquerading as age-related macular degeneration in elderly individuals., Methods: APMPPE or PPM eyes in patients above age 55 years with macular retinal pigment epithelium disruption including drusenoid lesions on macular examination and/or with multimodal imaging were included. At least one method of multimodal imaging including fluorescein angiography (FA), indocyanine green angiography, optical coherence tomography (OCT), and OCT angiography (OCTA) was performed in all eyes for diagnosis and to monitor for macular neovascularization., Results: Eight elderly male patients presented with vision loss and were all initially diagnosed with non-neovascular or neovascular age-related macular degeneration. With the aid of multimodal retinal imaging, a final diagnosis of either APMPPE or PPM was rendered. With FA and indocyanine green angiography, choroidal hypoperfusion was detected in all but one eye. With OCT, the angular sign of Henle fiber layer hyperreflectivity was identified in >50% of eyes. With OCTA, inner choroidal flow deficits were detected in all eyes. Macular neovascularization requiring anti-vascular endothelial growth factor injection therapy complicated three of eight cases., Conclusion: Both APMPPE and PPM may develop in elderly individuals and may masquerade as age-related macular degeneration on presentation. Multimodal imaging including FA, indocyanine green angiography, and OCTA are important diagnostic modalities to assess for inner choroidal hypoperfusion to arrive at an accurate diagnosis and to detect macular neovascularization, which frequently complicates APMPPE and PPM. In these patients, serial anti-vascular endothelial growth factor intravitreal injections are essential in treating macular neovascularization and in preventing significant vision loss.

Background: Superoxide dismutase 1 (SOD1) is one of the most important participants of antioxidant enzyme system in biological system. Previous studies have found that SOD1 is associated with many inflammatory diseases. The goal of this study was to assess the associations of serum SOD1 with the severity and prognosis in community-acquired pneumonia (CAP) patients by a prospective cohort study., Methods: CAP patients were enrolled from the Second Affiliated Hospital of Anhui Medical University. Peripheral blood samples were gathered. The level of serum SOD1 was detected through enzyme linked immunosorbent assay (ELISA). Clinical characteristics and demographic information were analyzed., Results: The level of serum SOD1 was gradually upregulated with elevated CAP severity scores. Spearman correlation coefficient or Pearson rank correlation analyses indicated that serum SOD1 was strongly connected with many clinical parameters among CAP patients. Further linear and logistic regression analyses found that the level of serum SOD1 was positively associated with CRB-65, CURB-65, SMART-COP, and CURXO scores among CAP patients. Moreover, serum higher SOD1 at admission substantially increased the risks of ICU admission, mechanical ventilation, vasoactive agent usage, death, and longer hospital stays during hospitalization. Serum SOD1 level combination with CAP severity scores elevated the predictive abilities for severity and death compared with alone serum SOD1 and CAP severity scores in CAP patients during hospitalization., Conclusion: The level of serum SOD1 is positively associated with the severity and poor prognosis in CAP patients, suggesting that SOD1 is implicated in the initiation and progression of CAP. Serum SOD1 may be regarded as a biomarker to appraise the severity and prognosis for CAP patients., Competing Interests: Declaration of competing interest All authors have declared that no competing interest existed., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Objectives: To provide an updated summary of published anchor-based Minimally Important Difference (MID) estimates for the EQ-5D index and EQ visual analog scale (EQ VAS) scores and identify factors influencing those estimates., Study Design and Setting: We systematically searched eight electronic databases from January 1990 to March 2023. We examined the association of baseline score, type of score change (improvement/worsening), data source, value set, disease/condition, treatment type (surgical/non-surgical), and type of anchor (clinical vs. self-rated) with MID estimates for the EQ-5D-3L and EQ-5D-5L indices, and EQ VAS. Significant variables were used to develop prediction formulas for MID by testing both linear and nonlinear regression models., Results: Of 6786 records reviewed, 47 articles were included for analysis. MID ranges for improved scores were -0.13 to 0.68 (EQ-5D-3L), 0.01-0.41 (EQ-5D-5L), and 0.42-23.0 (EQ VAS). Surgical intervention and lower baseline scores were associated with higher MIDs for both the EQ indices but not for EQ VAS. The nonlinear polynomial model outperformed the linear model in predicting the MIDs. MIDs based on deteriorated scores were insufficient for quantitative synthesis (mean: -0.02 for EQ-5D-3L; -0.04 for EQ-5D-5L; and -6.5 for EQ VAS)., Conclusion: This review revealed that the MID of EQ-5D index scores varies with baseline score and treatment type, indicating that use of a uniform MID may not be appropriate. We recommend using baseline score-adjusted and treatment type-specific EQ-5D MIDs, and call for more MID research, particularly in the context of assessing deterioration in health using this widely used generic health-status instrument., Competing Interests: Declaration of competing interest Dr Nan Luo and Dr Michael Herdman are members of the EuroQol Group. No other disclosures were reported., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Hinokiflavone (HF), classified as a flavonoid, is a main bioactive compound in Platycladus orientalis and Selaginella. HF exhibits activities including anti-HIV, anti-inflammatory, antiviral, antioxidant and anti-tumor effects. The study aimed to explore the function and the mechanisms of HF on acetaminophen (APAP)-induced acute liver injury. Results indicated that HF treatment mitigated the impact of APAP on viability and restored levels of MDA, GSH and SOD on HepG2 cells. The accumulation of reactive oxygen species (ROS) mitochondrial membrane potential (MMP) in HepG2 cells stimulated by APAP were also blocked by HF. HF reduced the levels of pro-apoptotic and pro-pyroptotic proteins. Flow cytometry analysis and fluorescence staining results were consistent with western blot analysis. Following HF treatment in the APAP-induced cell model, there was observed an augmentation in the phosphorylation of Stat3 and an increase in the expression of SIX4. However, not only silenced the SIX4 protein in HepG2 cells by siRNA, but also adding the Stat3 inhibitor (Stattic), attenuated the anti-apoptotic and anti-pyroptotic effects of HF significantly. Furthermore, HF alleviated liver damage in C57BL/6 mice model. Overall, our study demonstrated that HF mitigates apoptosis and pyroptosis induced by APAP in drug-induced liver injury (DILI) through the SIX4/Akt/Stat3 pathway in vivo and in vitro. HF may have promising potential for for the treatment of DILI., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Because some hypnotics worsen respiratory conditions, it was important to determine the respiratory safety of lemborexant, a competitive dual orexin-receptor antagonist approved to treat adults with insomnia, in subjects with moderate-to-severe chronic obstructive pulmonary disease. E2006-A001-113 (Study 113; NCT04647383) was a multicentre, multiple-dose, randomised, double-blind, placebo-controlled, two-period crossover study in adult subjects with moderate or severe chronic obstructive pulmonary disease (per spirometry-based Global Initiative for Chronic Obstructive Lung Disease [GOLD] criteria). Subjects (N = 30) were randomised to two treatment sequences comprising 8-night treatment periods (washout ≥ 14 days) with lemborexant 10 mg or placebo. Peripheral oxygen saturation (SpO 2 ; primary endpoint), apnea-hypopnea index, objective sleep parameters and sleep architecture measures were assessed after single (Day 1) and multiple (Day 8) doses. There was no significant difference in least-squares mean SpO 2 after a single dose of lemborexant (91.1%) versus placebo (91.5%). Although a statistically significant difference in SpO 2 was observed after multiple doses (least-squares mean: lemborexant, 91.3%; placebo, 90.8%) favouring lemborexant, this was not considered clinically meaningful. Apnea-hypopnea index was not significantly different between treatments after single or multiple doses. Total sleep time and total rapid eye movement sleep were significantly greater on Days 1 and 8 with lemborexant versus placebo. Treatment-emergent adverse events were reported in five (16.7%) subjects when taking lemborexant and four (13.3%) subjects when taking placebo; treatment-emergent adverse events were mostly mild. Lemborexant was well tolerated and did not adversely impact SpO 2 or apnea-hypopnea index after single and multiple doses relative to placebo in subjects with moderate-to-severe chronic obstructive pulmonary disease., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Family caregivers living with patients with dementia (PwD) face psychological challenges due to care burden. Technology-delivered psychosocial interventions (TPIs) have played a promising role in improving health outcomes among family caregivers living with PwD. This review aims to synthesise evidence of the effectiveness of TPIs on primary (burden and depression) and secondary outcomes (self-efficacy, stress and anxiety) for family caregivers living with PwD. Random-effects meta-analyses were performed to determine effect size. Using Cochran's Q and I 2 tests, statistical heterogeneity was evaluated. Sensitivity, subgroup analyses and meta-regression were employed to explain statistical heterogeneity. Twenty-eight trials comprising 4160 family caregivers from eight countries were included. Our meta-analysis revealed that TPIs resulted in slight reduction in depression, probably resulted in a slight reduction in burden and anxiety and slight increase in self-efficacy. Subgroup differences were detected in geographical regions (Western Pacific and Southeast Asia) for burden. While there were no significant subgroup differences in other factors, TPIs with preventive function and mobile applications had a more prominent larger effect size. Meta-regression analysis showed that attrition rate was a significant moderator on depression. Results are limited by the high risk of bias of included trials, which may reduce certainty of evidence. This review suggest TPIs are recommended as an adjunct treatment for alleviating burden and depressive outcomes in healthcare institutions. PROSPERO Registration Number: PROSPERO (CRD42023387962)., (© 2024 John Wiley & Sons Australia, Ltd.)

Adult zebrafish are able to heal large-sized cutaneous wounds in hours with little to no scarring. This rapid re-epithelialization is crucial for preventing infection and jumpstarting the subsequent regeneration of damaged tissues. Despite significant progress in understanding this process, it remains unclear how vast numbers of epithelial cells are orchestrated on an organismic scale to ensure the timely closure of millimeter-sized wounds. Here, we report an unexpected role of adult zebrafish appendages (fins) in accelerating the re-epithelialization process. Through whole-body monitoring of single-cell dynamics in live animals, we found that fin-resident epithelial cells (FECs) are highly mobile and migrate to cover wounds in nearby body regions. Upon injury, FECs readily undergo organ-level mobilization, allowing for coverage of body surfaces of up to 4.78 mm 2 in less than 8 h. Intriguingly, long-term fate-tracking experiments revealed that the migratory FECs are not short-lived at the wound site; instead, the cells can persist on the body surface for more than a year. Our experiments on "fin-less" and "fin-gaining" individuals demonstrated that the fin structures are not only capable of promoting rapid re-epithelialization but are also necessary for the process. We further found that fin-enriched extracellular matrix laminins promote the active migration of FECs by facilitating lamellipodia formation. These findings lead us to conclude that appendage structures in regenerative vertebrates, such as fins, may possess a previously unrecognized function beyond serving as locomotor organs. The appendages may also act as a massive reservoir of healing cells, which speed up wound closure and tissue repair., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Pain is one of the most common and harmful symptoms experienced by individuals with acute herpetic neuralgia (AHN). In this population, studies to determine the causes that affect patients taking medications compliance are rare. This study aimed to construct a predictive model for medication compliance of patients with AHN and to verify its performance., Design and Methods: In this prospective study of 398 patients with AHN who were discharged from a tertiary hospital with medications from July 2020 to October 2022, we used logistic regression analysis to explore the predictive factors of medication compliance of patients with AHN and to construct a nomogram. The area under the curve was used to evaluate the predictive effect of the model., Results: A predictive model of drug compliance of patients with AHN was constructed based on the following four factors: disease duration, pain severity before treatment, medication beliefs, and comorbidity of chronic diseases. The area under the curve of the model was 0.766 (95% confidence interval [0.713, 0.819]), with a maximum Youden's index of 0.431, sensitivity of 0.776, and specificity of 0.655. A linear calibration curve was found with a slope close to 1., Conclusions: The prediction model constructed in this study had good predictive performance and provided a reference for early clinical screening of independent factors that affected the medication compliance of patients with AHN., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Non-ST-segment elevation myocardial infarction (NSTEMI) is a common form of coronary artery disease, and its prognosis is influenced by multiple factors. This study aimed to analyze the predictive role of the combined application of cardiac troponin and cardiac function indices in NSTEMI patients' prognosis., Methods: NSTEMI patients were screened and included in the study. Cardiac troponin elevation ratio (cardiac troponin I (cTnI)/upper limit of normal (ULN)) was measured upon admission, and cardiac function was assessed. General clinical data, laboratory parameters, Grace score, New York Heart Association (NYHA) functional class, complications, and mortality data were collected. The correlation between mortality in NSTEMI patients and clinical parameters was analyzed, and a nomogram prediction model for NSTEMI patient mortality was established., Results: A total of 252 NSTEMI patients were included. Female gender, elevated high-sensitivity C-reactive protein (H-CRP), left ventricular ejection fraction (LVEF) < 50%, NYHA class III and IV, and cTnI/ULN elevation by 36.25-fold were significantly independently associated with mortality outcomes. Multifactorial logistic analysis indicated that these indices remained associated with mortality. A nomogram model predicting NSTEMI patient mortality was constructed using these indices, with an area under the curve (AUC) of 0.911, sensitivity of 97.5%, and specificity of 72.8%. This predictive model outperformed the Grace score (AUC = 0.840)., Conclusions: In NSTEMI patients, a 36.25-fold increase in cTnI/ULN, coupled with NYHA class III and IV, independently predicted prognosis. We developed a nomogram model integrating cTnI/ULN and cardiac function indices, aiding clinicians in assessing risk and implementing early interventions for improved outcomes., Competing Interests: All the authors have no conflict of interest., (Copyright 2024, Hu et al.)

Graphene supported electrocatalysts have demonstrated remarkable catalytic performance for oxygen reduction reaction (ORR). However, their durability and cycling performance are greatly limited by Oswald ripening of platinum (Pt) and graphene support corrosion. Moreover, comprehensive studies on the mechanisms of catalysts degradation under 0.6-1.6 V versus RHE (Reversible Hydrogen Electrode) is still lacking. Herein, degradation mechanisms triggered by different defects on graphene supports are investigated by two cycling protocols. In the start-up/shutdown cycling (1.0-1.6 V vs. RHE), carbon oxidation reaction (COR) leads to shedding or swarm-like aggregation of Pt nanoparticles (NPs). Theoretical simulation results show that the expansion of vacancy defects promotes reaction kinetics of the decisive step in COR, reducing its reaction overpotential. While under the load cycling (0.6-1.0 V vs. RHE), oxygen containing defects lead to an elevated content of Pt in its oxidation state which intensifies Oswald ripening of Pt. The presence of vacancy defects can enhance the transfer of electrons from graphene to the Pt surface, reducing the d-band center of Pt and making it more difficult for the oxidation state of platinum to form in the cycling. This work will provide comprehensive understanding on Pt/Graphene catalysts degradation mechanisms., (© 2024 Wiley‐VCH GmbH.)

Objective: Static assignment of participants in randomized clinical trials to placebo or ineffective treatment confers risk from continued seizures. An alternative trial design of time to exceed prerandomization monthly seizure count (T-PSC) has replicated the efficacy conclusions of traditionally designed trials, with shorter exposure to placebo and ineffective treatment. Trials aim to evaluate efficacy as well as safety and tolerability; therefore, we evaluated whether this T-PSC design also could replicate the trial's safety and tolerability conclusions., Methods: We retrospectively applied the T-PSC design to analyze treatment-emergent adverse events (TEAEs) from a blinded, placebo-controlled trial of perampanel for primary generalized tonic-clonic seizures (NCT01393743). The safety analysis set consisted of 81 and 82 participants randomized to perampanel and placebo arms, respectively. We evaluated the incidences of TEAEs, treatment-related TEAEs, serious TEAEs, and TEAEs of special interest that occurred before T-PSC relative to those observed during the full-length trial., Results: Of the 67 and 59 participants who experienced TEAEs in the perampanel and placebo arms during full-length trial, 66 (99%) and 54 (92%) participants experienced TEAEs with onset occurring before T-PSC, respectively. When limited to treatment-related TEAEs, 55 of 56 (98%) and 32 of 37 (86%) participants reported treatment-related TEAEs that occurred before T-PSC in the perampanel and placebo arms, respectively. There were more TEAEs after T-PSC with placebo as compared to perampanel (Fisher exact odds ratio = 8.6, p = .035), which resulted in overestimation of the difference in TEAE rate. There was a numerical reduction in serious TEAEs (3/13 occurred after T-PSC, one in placebo and two in perampanel)., Significance: Almost all TEAEs occurred before T-PSC. More treatment-related TEAEs occurred after T-PSC for participants randomized to placebo than perampanel, which may be due to either a shorter T-PSC or delayed time to TEAE for placebo., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: circRNAs have been shown to participate in diverse diseases; however, their role in oral submucous fibrosis (OSF), a potentially malignant disorder, remains obscure. Our preliminary experiments detected the expression of circRNA mitochondrial translation optimization 1 homologue (circMTO1) in OSF tissues (n = 20) and normal mucosa tissues (n = 20) collected from Hunan Xiangya Stomatological Hospital, and a significant decrease of circMTO1 expression was showed in OSF tissues. Therefore, we further explored circMTO1 expression in OSF., Methods: Target molecule expression was detected using RT-qPCR and western blotting. The migration and invasion of buccal mucosal fibroblasts (BMFs) were assessed using wound healing and Transwell assays. The interaction between miR-30c-5p, circMTO1, and SOCS3 was evaluated using dual luciferase, RNA immunoprecipitation (RIP), and RNA pull-down assays. The colocalisation of circMTO1 and miR-30c-5p was observed using fluorescence in situ hybridisation (FISH)., Results: circMTO1 and SOCS3 expression decreased, whereas miR-30c-5p expression increased in patients with OSF and arecoline-stimulated BMFs. Overexpression of circMTO1 effectively restrained the fibroblast-myofibroblast transition (FMT), as evidenced by the increase in expression of Coll I, α-SMA, Vimentin, and the weakened migration and invasion functions in BMFs. Mechanistic studies have shown that circMTO1 suppresses FMT by enhancing SOCS3 expression by sponging miR-30c-5p and subsequently inactivating the FAK/PI3K/AKT pathway. FMT induced by SOCS3 silencing was reversed by the FAK inhibitor TAE226 or the PI3K inhibitor LY294002., Conclusion: circMTO1/miR-30c-5p/SOCS3 axis regulates FMT in arecoline-treated BMFs via the FAK/PI3K/AKT pathway. Expanding the sample size and in vivo validation could further elucidate their potential as therapeutic targets for OSF., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study examines the impact of Human-Drone Interaction (HDI) modalities on construction workers' safety and balance control within virtual environments. Utilising virtual reality (VR) simulations, the study explored how gesture and speech-based communications influence workers' physical postures and balance, contrasting these modalities with a non-interactive control group. One hundred participants were recruited, and their movements and balance control were tracked using motion sensors while they interacted with virtual drones through either gesture, speech, or without communication. Results showed that interactive modalities significantly improved balance control and reduced the risk of falls, suggesting that advanced HDI can enhance safety on construction sites. However, speech-based interaction increased cognitive workload, highlighting a trade-off between physical safety and mental strain. These findings underscore the potential of integrating intuitive communication methods into construction operations, although further research is needed to optimise these interactions for long-term use and in diverse noise environments.

Competing Interests: Disclosure of competing interest: The authors have no conflicts of interest or proprietary interests to disclose.

Objectives: This review aims to examine the ceiling effects of EQ-5D-3L (3L) and EQ-5D-5L (5L) in general adult populations and identify the factors influencing these effects., Methods: We searched 8 databases for observational studies published in English from inception to 24 July 2023. Ceiling effects were calculated by dividing the number of participants reporting full health at dimension or profile level by the total sample size. Subgroup analysis and meta-regression using the metafor package in R software were performed., Results: We identified 94 studies from 70 articles, including 4 543 647 adults across 37 countries. The global pooled proportion of individuals reporting full health ("11111") was 56% (95% CI 51%-62%) for 3L and 49% (95% CI 44%-54%) for 5L. The self-care dimension showed the highest ceiling effects (3L: 97%; 5L: 94%), whereas pain/discomfort had the lowest (3L: 69%; 5L: 60%). The ceiling effects in East/South-East Asia were higher than in Europe by 25% (95% CI 18%-32%) in 3L and 9% (95% CI -2%-20%) in 5L. Adjusting for mean age and proportion of males, significant regional differences persisted in the overall profile level of 3L, in all 3L dimensions (except for self-care), and 5L dimensions (except for pain/discomfort and anxiety/depression)., Conclusions: This review highlights significant ceiling effects in the EQ-5D, especially in Asian populations. The 5L version exhibited fewer ceiling effects than the 3L, indicating its superiority for general population surveys. Further research is crucial to understand the disparities in self-reported health outcomes between Asians and other populations., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Lithium-ion batteries with Li 3 V 2 (PO 4 ) 3 /C as the cathode have been a popular research topic in recent years; however, studies of the effects of external magnetic fields on them are less common. This study investigates the effects of an external magnetic field applied parallel to the direction of the anode and cathode on the ion transport through iron-doped Li 3 (V 1- x Fe x ) 2 (PO 4 ) 3 , the outer carbon coating, the film/electrolyte/separator, and up to the lithium metal electrode on a microscopic level. The results reveal that for the x = 0.05 sample with lower doping, the magnetostriction expansion of Li 3 (V 1- x Fe x ) 2 (PO 4 ) 3 and the magnetostrictive contraction effect of the outer ordered carbon layer cancel each other out, resulting in no significant enhancement of the battery's energy and power density due to the external magnetic field. In contrast, the x = 0.1 sample, lacking magnetostrictive contraction in the outer ordered carbon layer, shows that its energy and power density can be influenced by the magnetic field. Under zero magnetic field, the cyclic performance exhibits superior average capacity performance in the x = 0.05 sample, while the x = 0.1 sample shows a lower decay rate. Both samples are affected by the magnetic field; however, the x = 0.1 sample performs better under magnetic conditions. In particular, in the C-rate tests under a magnetic field, the sample with x = 0.1 showed a significant relative reduction in capacity decay rate by 20.18% compared to the sample with x = 0.05., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Contrast enhanced pulmonary vein magnetic resonance angiography (PV CE-MRA) has value in atrial ablation pre-procedural planning. We aimed to provide high fidelity, ECG gated PV CE-MRA accelerated by variable density Cartesian sampling (VD-CASPR) with image navigator (iNAV) respiratory motion correction acquired in under 4 min. We describe its use in part during the global iodinated contrast shortage. VD-CASPR/iNAV framework was applied to ECG-gated inversion and saturation recovery gradient recalled echo PV CE-MRA in 65 patients (66 exams) using .15 mmol/kg Gadobutrol. Image quality was assessed by three physicians, and anatomical segmentation quality by two technologists. Left atrial SNR and left atrial/myocardial CNR were measured. 12 patients had CTA within 6 months of MRA. Two readers assessed PV ostial measurements versus CTA for intermodality/interobserver agreement. Inter-rater/intermodality reliability, reproducibility of ostial measurements, SNR/CNR, image, and anatomical segmentation quality was compared. The mean acquisition time was 3.58 ± 0.60 min. Of 35 PV pre-ablation datasets (34 patients), mean anatomical segmentation quality score was 3.66 ± 0.54 and 3.63 ± 0.55 as rated by technologists 1 and 2, respectively (p = 0.7113). Good/excellent anatomical segmentation quality (grade 3/4) was seen in 97% of exams. Each rated one exam as moderate quality (grade 2). 95% received a majority image quality score of good/excellent by three physicians. Ostial PV measurements correlated moderate to excellently with CTA (ICCs range 0.52-0.86). No difference in SNR was observed between IR and SR. High quality PV CE-MRA is possible in under 4 min using iNAV bolus timing/motion correction and VD-CASPR., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Colitis is a common manifestation of immune checkpoint inhibitor (ICI) toxicity and can present with varied histologic patterns of inflammation, some of which have been shown to be associated with specific ICI drug types. Although the histologic features of ICI colitis seen at the time of diagnosis have been described, there have been few reports following these patients over time. We evaluated initial and follow-up biopsies in 30 patients with ICI colitis and found that 37% of patients developed a different pattern of injury on follow-up biopsy compared to the initial biopsy. Patients with a different inflammatory pattern were more likely to have restarted ICI therapy before their follow-up biopsy (64%) compared to those without a change in inflammatory pattern (11%; P < 0.01). The majority of these patients had changed ICI drug types (86%). Additionally, many cases changed to an inflammatory bowel disease (IBD)-like pattern (36%), raising a question of de novo IBD. However, all of our patients with an IBD-like pattern experienced sustained resolution of symptoms without steroids or other immunosuppressive medications following discontinuation of ICI therapy, consistent with a diagnosis of ICI toxicity. Our findings suggest that follow-up biopsies in patients with ICI colitis may show a different histology and that this does not necessarily warrant a change in the histologic diagnosis to another disease., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The pore structure of carbon anodes plays a crucial role in enhancing the sodium storage capacity. Designing more confined pores in carbon anodes is accepted as an effective strategy. However, current design strategies for confined pores in carbon anodes fail to achieve both high capacity and initial Coulombic efficiency (ICE) simultaneously. Herein, we develop a strategy for utilizing the repeated impregnation and precarbonization method of liquid pitch to regulate the pore structure of the activated carbon (AC) material. Driven by capillary coalescence, the pitch is impregnated into the pores of AC, which reduces the specific surface area of the material. During the carbonization process, numerous pores with diameters less than 1 nm are formed, resulting in a high capacity and improved ICE of the carbon anode. Moreover, the ordered carbon layers derived from the liquid pitch also enhance the electrical conductivity, thereby improving the rate capability of as-obtained carbon anodes. This enables the fabricated material (XA-4T-1300) to have a high ICE of 91.1% and a capacity of 383.0 mA h g -1 at 30 mA g -1 . The capacity retention is 95.5% after 300 cycles at 1 A g -1 . This study proposes a practical approach to adjust the microcrystalline and pore structures to enhance the performance of sodium-ion storage in materials.

Electric fields (EF) play an essential role in cancer cell migration. Numerous cancer cell types exhibit electrotaxis under direct current electric fields (dcEF) of physiological electric field strength (EFs). This study investigated the effects of doxycycline on the electrotactic responses of U87 cells. After EF stimulation, U87 cells migrated toward the cathode, whereas doxycycline-treated U87 cells exhibited enhanced cell mobility but hindered cathodal migration. We further investigated the expression of the metastasis-correlated proteins matrix metallopeptidase-2 (MMP-2) and MMP-9 in U87 cells. The levels of MMP-2 in the cells were not altered under EF or doxycycline stimulation. In contrast, the EF stimulation greatly enhanced the levels of MMP-9 and then repressed in doxycycline-cotreated cells, accompanied by reduced cathodal migration. Our results demonstrated that an antibiotic at a non-toxic concentration could suppress the enhanced cell migration accelerated by EF of physiological strength. This finding may be applied as an anti-metastatic treatment for cancers., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors.)

Purpose: Patients with gynaecological cancer often experience psychological issues due to multiple stressors. Psychological disturbances have debilitating effects on patients with gynaecological cancer. In recent decades, digital psychosocial interventions have rapidly advanced and been incorporated into mental health interventions. Digital psychosocial interventions could provide patients with several benefits over traditional in-person interventions, including convenience, anonymity, flexible scheduling, and geographic mobility. The aim of this systematic review was to synthesize the effectiveness of digital psychosocial intervention in reducing psychological distress, depression, and anxiety and improving health-related quality of life in patients with gynaecological cancer., Methods: Three-step extensive search was performed on 22 December 2022 from nine bibliographic databases, trial registries and grey literature. Experimental studies involving patients with gynaecological cancer utilizing digital psychosocial interventions for the improvement of mental health outcomes were included. Meta-analysis was conducted using RevMan 5.4 software. Heterogeneity was analysed by Cochran's Q test and I 2 . Subgroup analyses were attempted to evaluate relative effect sizes of subgroup features., Results: Meta-analysis of nine studies revealed small effect size in reduction of depression post-intervention (d = 0.24, 95% CI - 0.46 to - 0.02) and medium effect size in reduction of psychological distress post-intervention (d = 0.51, 95% CI - 0.81 to - 0.21) and follow-up (d = 0.65, 95% CI - 1.25 to - 0.05) compared to the control group. The effects of digital psychosocial interventions on anxiety and health-related quality of life were not statistically significant., Conclusions: Digital psychosocial interventions probably reduced psychological distress and slightly reduced depression amongst patients with gynaecological cancer compared to the control group, which can be integrated into clinical practice. Additional trials with rigorous methodology and bigger sample sizes are needed to validate findings., Trial Registration: PROSPERO (CRD42023389502)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: The aim of this study is to determine the cumulative amount of lemborexant (a competitive dual orexin receptor antagonist approved to treat adults with insomnia) excreted in human breast milk and the relative infant dose (RID) as a proportion of daily maternal dose., Methods: E2006-A001-010 was a single-centre, open-label study that enrolled lactating women (≥18 years) who breastfed for ≥5 weeks postpartum. After overnight fasting, subjects received a single 10-mg oral dose of lemborexant. Using a standardized electric pump, milk was sampled before and ≤240 h (10 days) after dosing; combined and total volume were recorded. The cumulative total amount of lemborexant excreted, fraction of dose excreted, daily infant dose and RID were calculated. Lemborexant concentration in human milk was assessed by liquid chromatography with tandem mass spectrometry., Results: Eight subjects completed the study. The mean cumulative total amount of lemborexant reached 0.0174 mg (coefficient of variation [CV] 54.5%; 0.174% of lemborexant 10 mg administered) in breast milk at 240 h (10 days); ~70% of excreted lemborexant accumulated in the first 24 h. For an infant weighing 6 kg, the daily infant dose was 0.00290 mg kg -1 (CV 54.5%) and the RID was 1.96% (CV 63.1%) of daily maternal dose. Mild treatment-emergent adverse events were reported in 4 subjects; these all resolved by end of study., Conclusion: Trace quantities of lemborexant were found in human breast milk. Lemborexant was well tolerated by healthy lactating women., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Study Objectives: To evaluate the respiratory safety of lemborexant among adults and older adults with moderate to severe obstructive sleep apnea (OSA)., Methods: E2006-A001-113 (Study 113; NCT04647383) was a double-blind, two-period crossover, placebo-controlled study in adults (ages ≥ 45 to ≤ 90 years, n = 33) with moderate (apnea-hypopnea index [AHI] score ≥ 15 to < 30 events/h, n = 13) or severe (AHI ≥ 30 events/h, n = 20) OSA. Participants were randomized to lemborexant 10 mg (LEM10) or placebo (PBO) for two treatment periods of 8 nights with a ≥ 14-day washout period. AHI and peripheral oxygen saturation were evaluated after treatment on Day 1 (after a single dose) and Day 8 (after multiple doses)., Results: No significant differences in AHI were observed after single and multiple doses of LEM10 compared with PBO in participants with moderate to severe OSA (least-squares mean: single-dose LEM10, 41.7; PBO, 44.8; multiple-dose LEM10, 44.9; PBO, 45.7). In addition, there were no significant differences between treatments in peripheral oxygen saturation (least-squares mean: single-dose LEM10, 93.0; PBO, 93.1; multiple-dose LEM10, 93.1; PBO, 93.4). Further, there were no significant differences between treatments in percentage of total sleep time with peripheral oxygen saturation < 90%, < 85%, or < 80%. No significant differences were observed between treatments when AHI and peripheral oxygen saturation outcomes were analyzed by OSA severity. Altogether, 6/33 (18.2%) participants receiving LEM10, vs 3/33 (9.1%) PBO, reported treatment-emergent adverse events, mostly mild in severity., Conclusions: LEM10 demonstrated respiratory safety and was well tolerated with single-dose and multiple-dose administration in participants with moderate to severe OSA. This suggests that LEM may be a treatment option for patients with OSA and comorbid insomnia., Clinical Trial Registration: Registry: ClinicalTrials.gov; Name: A Study to Evaluate the Respiratory Safety of Lemborexant in Adult and Elderly Participants With Moderate to Severe Obstructive Sleep Apnea and in Adult and Elderly Participants With Moderate to Severe Chronic Obstructive Pulmonary Disease; URL: https://clinicaltrials.gov/ct2/show/NCT04647383; Identifier: NCT04647383., Citation: Cheng JY, Lorch D, Lowe AD, et al. A randomized, double-blind, placebo-controlled, crossover study of respiratory safety of lemborexant in moderate to severe obstructive sleep apnea. J Clin Sleep Med . 2024;20(1):57-65., (© 2024 American Academy of Sleep Medicine.)

Cutibacterium acnes is a commensal bacterium on the skin that is generally well-tolerated, but different strain types have been hypothesized to contribute to the disease acne vulgaris. To understand how some strain types might contribute to skin inflammation, we generated a repository of C. acnes isolates from skin swabs of healthy subjects and subjects with acne and assessed their strain-level identity and capacity to stimulate cytokine release. Phylotype II K-type strains were more frequent on healthy and nonlesional skin of subjects with acne than those isolated from lesions. Phylotype IA-1 C-type strains were increased on lesional skin compared with those on healthy skin. The capacity to induce cytokines from cultured monocyte-derived dendritic cells was opposite to this action on sebocytes and keratinocytes and did not correlate with the strain types associated with the disease. Whole-genome sequencing revealed a linear plasmid in high-inflammatory isolates within similar strain types that had different proinflammatory responses. Single-cell RNA sequencing of mouse skin after intradermal injection showed that strains containing this plasmid induced a higher inflammatory response in dermal fibroblasts. These findings revealed that C. acnes strain type is insufficient to predict inflammation and that carriage of a plasmid could contribute to disease., (Copyright © 2023. Published by Elsevier Inc.)

The period of the year from spring to fall, when clocks in most parts of the United States are set one hour ahead of standard time, is called daylight saving time, and its beginning and ending dates and times are set by federal law. The human biological clock is regulated by the timing of light and darkness, which then dictates sleep and wake rhythms. In daily life, the timing of exposure to light is generally linked to the social clock. When the solar clock is misaligned with the social clock, desynchronization occurs between the internal circadian rhythm and the social clock. The yearly change between standard time and daylight saving time introduces this misalignment, which has been associated with risks to physical and mental health and safety, as well as risks to public health. In 2020, the American Academy of Sleep Medicine (AASM) published a position statement advocating for the elimination of seasonal time changes, suggesting that evidence best supports the adoption of year-round standard time. This updated statement cites new evidence and support for permanent standard time. It is the position of the AASM that the United States should eliminate seasonal time changes in favor of permanent standard time, which aligns best with human circadian biology. Evidence supports the distinct benefits of standard time for health and safety, while also underscoring the potential harms that result from seasonal time changes to and from daylight saving time., Citation: Rishi MA, Cheng JY, Strang AR, et al. Permanent standard time is the optimal choice for health and safety: an American Academy of Sleep Medicine position statement. J Clin Sleep Med . 2024;20(1):121-125., (© 2024 American Academy of Sleep Medicine.)