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Chuan Zou,* Shanping Chen,* Jing Shen, Xiaomei Zheng, Lingxiao Wang, Lijuan Guan, Qian Liu, Yongxue Yang Department of Gerontology and Geriatrics, Chengdu Fifth People’s Hospital, Chengdu-Montpellier Geri­atric Research Center, Chengdu, China *These authors contributed equally to this work Background: Depression in the elderly is a serious and often underdiagnosed psychiatric disorder that has been linked to adverse outcomes in the hospital setting. This study aims to evaluate the prevalence of depressive symptoms and associated factors among elderly hospital inpatients. Methods: The cross-sectional study included 411 consecutively hospitalized patients aged 60 years and older. Participants were evaluated within 48 hours of admission using an interviewer-administered questionnaire including the Geriatric Depression Scale and comprehensive geriatric assessment to provide basic demographic and clinical information. Results: Most of the participants were male (64.5%), with a mean (SD) age of 75.9 (8.1) years between 60 and 97 years. The prevalence of depressive symptoms was 32.8%. Univariate analysis showed significant associations between depressive symptoms and older age, female gender, lower body mass index, number of chronic diseases, impaired family function, impaired cognition, malnutrition, increased frailty, and decreased ability to perform activities of daily living. After logistic regression, variables that remained significantly associated with depression were cognitive decline (odds ratio =1.97, 95% CI: 1.09–3.55), poor family function (odds ratio =2.01, 95% CI: 1.10–3.66), and frailty (odds ratio =5.07, 95% CI: 1.95–13.20). Depressive symptoms were independently associated with prolonged hospital length. Conclusion: Depressive symptoms were prevalent among hospitalized elderly and independently associated with cognitive decline, poor family function, and frailty. Therefore, it is essential to screen for depression and perform a comprehensive geriatric assessment in these patients to identify and manage depressive symptoms. Keywords: depressive symptoms, aged, inpatients, prevalence, comprehensive geriatric assessment

During the shutdown of the CERN Large Hadron Collider in 2013-2014, an additional pixel layer was installed between the existing Pixel detector of the ATLAS experiment and a new, smaller radius beam pipe. The motivation for this new pixel layer, the Insertable B-Layer (IBL), was to maintain or improve the robustness and performance of the ATLAS tracking system, given the higher instantaneous and integrated luminosities realised following the shutdown. Because of the extreme radiation and collision rate environment, several new radiation-tolerant sensor and electronic technologies were utilised for this layer. This paper reports on the IBL construction and integration prior to its operation in the ATLAS detector.

Endovascular aortic aneurysm repair is a minimally invasive procedure with low mortality and morbidity. Clinical studies have revealed that a displacement force (DF) can cause stent graft (SG) migration in some circumstances requiring repeated intervention. This study aims to determine the relationship between the SG curvature and the calculated DF from four patient-specific computational fluid dynamics models. The SG's curvature was defined according to the centrelines of the implanted SG's branches. The centrelines were defined as either intersecting or separated lines. The centreline curvature (CLC) metrics were calculated based on the local curvature radii and the distances from the centrelines of idealized straight branches. The average CLC value and average variation were calculated to represent the entire graft's curvature. These CLC calculations were compared, and the method that gave the best correlation to the calculated DF was found. The optimal correlation is obtained from calculating the CLC average variation using separated centrelines and distance from straight lines, with an R2 = 0.89. Understanding the relationship between vascular morphology and DF can help identify at-risk patients before the procedure. In these cases, we can provide appropriate treatment and follow up with the patient to prevent future failure.

Using entry and re-entry analysis we report a simple technique designed to solely manage the fenestrations in an aortic aneurysm caused by chronic type A or B dissections. With meticulous computed tomography mapping of each fenestration, endovascular management can be customized to those areas only. Several cases are presented using this selective approach resulting in durable thrombosis of the false lumen. Targeted coverage of fenestrations in a chronic type B dissecting aneurysm is a feasible and effective management option resulting in reliable false lumen occlusion whilst maintaining visceral perfusion.

The chimney endovascular aortic repair technique is an established option for the treatment of juxtarenal aortic aneurysms. Failure of this repair represents a major surgical challenge. We report the case of a patient treated previously with chimney endovascular aortic repair (for a juxtarenal aortic aneurysm), who had developed a large type IA endoleak. The patient was treated with a custom-made endograft with three inner branches. All vessels were successfully cannulated and bridged, no evidence of endoleak was seen on the completion angiogram, and the patient had an uneventful recovery.

SUMMARY We elucidated the molecular epidemiology and evolution of Japanese encephalitis virus (JEV) strains isolated from 1949 to 2009 in China in this study. Three genotypes (I, III, V) were confirmed to be co-circulating in China in both high- and low-prevalence areas. Genotype III consisted of two clades (mainland clade and Taiwan clade). Compared to the mainland clade, genotype I and the Taiwan clade were newly introduced and evolved more rapidly. We also demonstrated that JEV strains in China, especially those in the mainland clade, were not only under purifying selection, but also probably under positive selection (aa 227 and 408 in the envelope protein). [ABSTRACT FROM AUTHOR]

Background: To gain a comprehensive understanding of the altered sensory processing in patients with migraine, in this study, we developed an electroencephalography (EEG) protocol for examining brainstem and cortical responses to sensory stimulation. Furthermore, machine learning techniques were employed to identify neural signatures from evoked brainstem-cortex activation and their interactions, facilitating the identification of the presence and subtype of migraine., Methods: This study analysed 1,000-epoch-averaged somatosensory evoked responses from 342 participants, comprising 113 healthy controls (HCs), 106 patients with chronic migraine (CM), and 123 patients with episodic migraine (EM). Activation amplitude and effective connectivity were obtained using weighted minimum norm estimates with spectral Granger causality analysis. This study used support vector machine algorithms to develop classification models; multimodal data (amplitude, connectivity, and scores of psychometric assessments) were applied to assess the reliability and generalisability of the identification results from the classification models., Results: The findings revealed that patients with migraine exhibited reduced amplitudes for responses in both the brainstem and cortical regions and increased effective connectivity between these regions in the gamma and high-gamma frequency bands. The classification model with characteristic features performed well in distinguishing patients with CM from HCs, achieving an accuracy of 81.8% and an area under the curve (AUC) of 0.86 during training and an accuracy of 76.2% and an AUC of 0.89 during independent testing. Similarly, the model effectively identified patients with EM, with an accuracy of 77.5% and an AUC of 0.84 during training and an accuracy of 87% and an AUC of 0.88 during independent testing. Additionally, the model successfully differentiated patients with CM from patients with EM, with an accuracy of 70.5% and an AUC of 0.73 during training and an accuracy of 72.7% and an AUC of 0.74 during independent testing., Conclusion: Altered brainstem-cortex activation and interaction are characteristic of the abnormal sensory processing in migraine. Combining evoked activity analysis with machine learning offers a reliable and generalisable tool for identifying patients with migraine and for assessing the severity of their condition. Thus, this approach is an effective and rapid diagnostic tool for clinicians., (© 2024. The Author(s).)

Background: Castanopsis carlesii is a dominant tree species in subtropical evergreen broad-leaved forests and holds significant ecological value. It serves as an excellent timber tree species and raw material for cultivating edible fungi. Henry Chinquapin (Castanea henryi) wood is known for its hardness and resistance to water and moisture, making it an exceptional timber species. Additionally, its fruit has a sweet and fruity taste, making it a valuable food source. However, the mitogenomes of these species have not been previously reported. To gain a better understanding of them, this study successfully assembled high-quality mitogenomes of C. carlesii and Ca. henryi for the first time., Results: Our research reveals that the mitochondrial DNA (mtDNA) of C. carlesii exhibits a unique multi-branched conformation, while Ca. henryi primarily exists in the form of two independent molecules that can be further divided into three independent molecules through one pair of long repetitive sequences. The size of the mitogenomes of C. carlesii and Ca. henryi are 592,702 bp and 379,929 bp respectively, which are currently the largest and smallest Fagaceae mitogenomes recorded thus far. The primary factor influencing mitogenome size is dispersed repeats. Comparison with published mitogenomes from closely related species highlights differences in size, gene loss patterns, codon usage preferences, repetitive sequences, as well as mitochondrial plastid DNA segments (MTPTs)., Conclusions: Our study enhances the understanding of mitogenome structure and evolution in Fagaceae, laying a crucial foundation for future research on cell respiration, disease resistance, and other traits in this family., (© 2024. The Author(s).)

Background: Pre-cluster symptoms (PCSs) are symptoms preceding cluster bouts and might have implications for the treatment of cluster headache (CH). This study investigated the prevalence of PCSs, and their utility in predicting upcoming bouts as well as the associations with therapeutic efficacy., Methods: We prospectively collected data from patients with CH. Each patient received a structured interview and completed questionnaire surveys during CH bouts. In sub-study 1, we cross-sectionally analyzed the prevalence, symptomatology, and predictability of upcoming bouts. Overall, 34 PCSs, divided into seven categories, were queried, including head and neck pain, cranial autonomic symptoms, restlessness, fatigue or mood changes, sleep alterations, constitutional symptoms, and generalized pain. In sub-study 2, we recorded the weekly frequency of CH attacks after the initiation of verapamil concurrently with a 14-day transitional therapy based on the patients' headache diary. A responder to verapamil was defined as a patient who have a reduction from baseline of at least 50% in the weekly frequency of CH attacks 4 weeks after the initiation of verapamil., Results: A total of 168 CH patients (women/men: 39/129) completed the study. In sub-study 1, we found 149 (88.7%) experienced PCSs, with a median of 24 (IQR 18 to 72) hours before the bouts. Up to 57.7% of patients with PCS reported that they could predict upcoming bouts. Among the seven categories of PCSs, head and neck pain was the most common (81.0%) and was associated with a higher predictability of upcoming bouts (odds ratio [OR] = 4.0; 95% confidence interval [CI] 1.7-9.6). In sub-study 2, we found two categories of PCSs were associated with the response to verapamil: sleep alteration (OR = 2.5 [95% CI = 1.3-4.8], p = 0.004) and ≥ 1 cranial autonomic symptoms (OR = 2.7 [95% CI = 1.4-5.1], p = 0.003)., Conclusion: PCSs were very common in CH and could be used to predict upcoming bouts. Different symptom categories of PCSs may have different clinical implications., (© 2024. The Author(s).)

Background: Migraine-related perfusion changes are documented but inconsistent across studies due to limited sample size and insufficient phenotyping. The phasic and spatial dynamics across migraine subtypes remains poorly characterized. This study aimed to determine spatiotemporal dynamics of gray matter (GM) perfusion in migraine., Methods: We prospectively recruited episodic (EM) and chronic migraine (CM) patients, diagnosed with the International Headache Society criteria and healthy controls (HCs) between 2021 and 2023 from the headache center in a tertiary medical center, and adjacent communities. Magnetic resonance (3-tesla) arterial spin labeling (ASL) was conducted for whole brain cerebral blood flow (CBF) in all participants. The voxel-wise and whole brain gray matter (GM) CBF were compared between subgroups. Spatial pattern analysis of CBF and its correlations with headache frequency were investigated regarding different migraine phases and subtypes. Sex- and age-adjusted voxel-wise and whole brain GM comparisons were performed between HCs and different EM and CM phases. Spatial pattern analysis was conducted by CBF clusters with phasic differences and spin permutation test. Correlations between headache frequency and CBF were investigated regarding different EM and CM phases., Results: Totally 344 subjects (172 EM, 120 CM, and 52 HCs) were enrolled. Higher CBF in different anatomical locations was identified in ictal EM and CM. The combined panels of the specific locations with altered CBF in ictal EM on receiver operating characteristic curve analysis demonstrated areas under curve of 0.780 (vs. HCs) and 0.811 (vs. preictal EM). The spatial distribution of ictal-interictal CBF alteration of EM and CM were not correlated with each other (p = 0.665; r = - 0.018). Positive correlations between headache frequency and CBF were noted in ictal EM and CM regarding whole GM and specific anatomical locations., Conclusions: Patients with migraine exhibited unique spatiotemporal CBF dynamics across different phases and distinct between subtypes. The findings provide neurobiological insights into how selected anatomical structures engage in a migraine attack and adapt to plastic change of repeated attacks along with chronicity., (© 2024. The Author(s).)

Background: There have been limited data on idiopathic intracranial hypertension (IIH) in Asians and there remain uncertainties whether a cerebrospinal fluid (CSF) pressure of 250 mm CSF is an optimum diagnostic cutoff. The aims of the present study included (1) characterization of IIH patients in Taiwan, (2) comparisons among different diagnostic criteria for IIH, and (3) comparisons between patients with CSF pressures of > 250 and 200-250 mm CSF., Methods: This retrospective study involved IIH patients based on the modified Dandy criteria from two tertiary medical centers in Taiwan. Clinical manifestations were retrieved from electronic medical records, and findings on ophthalmologic examination and magnetic resonance images (MRIs) were reviewed., Results: A total of 102 patients (71 F/31 M, mean age 33.4 ± 12.2 years, mean CSF pressure 282.5 ± 74.5 mm CSF) were identified, including 46 (45.1%) with obesity (body-mass index ≥ 27.5), and 57 (62.6%) with papilledema. Overall, 80 (78.4%), 55 (53.9%), 51 (50.0%), and 58 (56.9%) patients met the Second and Third Edition of International Classification of Headache Disorders, Friedman, and Korsbæk criteria, respectively. Patients in the 200-250 mm CSF group (n = 40) were less likely to have papilledema (48.5% vs. 70.7%, p = 0.035), transient visual obscuration (12.5% vs. 33.9%, p = 0.005), and horizontal diplopia (10.0% vs. 30.6%, p = 0.006), and had fewer signs on MRIs (2.2 ± 1.3 vs. 2.8 ± 1.0, p = 0.021) when compared with those with CSF pressures > 250 mm CSF (n = 62). However, the percentages of patients with headache (95.0% vs. 87.1%, p = 0.109) at baseline, chronic migraine at six months (31.6% vs. 25.0%, p = 0.578), and visual field defect (86.7% vs. 90.3%, p = 0.709) were similar., Conclusions: It was found that obesity and papilledema were less common in Asian IIH patients when compared with Caucasian patients. Although patients with CSF pressures of 200-250 mm CSF had a less severe phenotype, the risks of having headache or visual loss were comparable to those in the > 250 mm CSF group. It is possible that a diagnostic cutoff of > 200 mm CSF could be more suitable for Asians, although further studies are still needed., (© 2024. The Author(s).)

Introduction: Recent immigrants from racialized minority backgrounds and those who are not proficient in the local language are some of the most vulnerable members of society. Despite having postsecondary educational qualifications and permanent residency status, many are engaged in precarious employment. There is a scarcity of research that has explicitly focused on the work experiences and mental health challenges faced by these immigrants., Methods: Using a grounded theory approach and semi-structured face-to-face interviews, this study examined the work experiences and mental health challenges of 42 recent immigrant employees from two cities in Canada who were working in various industries and engaged in precarious employment., Findings: Eighty-one percent of the employee participants were overqualified for their jobs. Findings highlighted several ongoing mental problems that participants experienced, stemming from challenging physical and psychological workplace conditions, negative mindsets associated with their recent immigrant status, and other contextual factors and barriers. However, various coping strategies, both constructive and unconstructive, were used to address this mental distress., Discussion: The study proposes a multidimensional approach to address workplace conditions to promote good mental health for these employees. This includes preventative programs for raising awareness among employers about the importance of recent immigrant employees' mental health and well-being and policy and legislation changes to ensure the employer's commitment to creating a safe and culturally friendly workplace. The approach also recommends that recent immigrant employees receive occupational health and safety training, learn about Canadian workplace norms and culture, and have access to professional healthcare services., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Shankar, Chen, Lai, Joseph, Narayanan, Suleman, Ali and Kharat.)

T cell acute lymphoblastic leukemia (T-ALL) is difficult to treat when it relapses after therapy or is chemoresistant; the prognosis of patients with relapsed or refractory T-ALL is generally poor. We report a case series of 17 such patients who received autologous chimeric antigen receptor (CAR) T cells expressing an anti-CD7 CAR and an anti-CD7 protein expression blocker (PEBL), which prevented CAR T cell fratricide. Despite high leukemic burden and low CAR T cell dosing, 16 of the 17 patients attained minimal residual disease-negative complete remission within 1 month. The remaining patient had CD7 - T-ALL cells before infusion, which persisted after infusion. Toxicities were mild: cytokine release syndrome grade 1 in ten patients and grade 2 in three patients; immune effector cell-associated neurotoxicity syndrome grade 1 in two patients. Eleven patients remained relapse-free (median follow-up, 15 months), including all nine patients who received an allotransplant. The first patient is in remission 55 months after infusion without further chemotherapy or transplantation; circulating CAR T cells were detectable for 2 years. T cells regenerating after lymphodepletion lacked CD7 expression, were polyclonal and responded to SARS-CoV-2 vaccination; CD7 + immune cells reemerged concomitantly with CAR T cell disappearance. In conclusion, autologous anti-CD7 PEBL-CAR T cells have powerful antileukemic activity and are potentially an effective option for the treatment of T-ALL., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background and Purpose: This study aimed to investigate early changes in interstitial fluid (ISF) flow in patients with severe carotid stenosis after carotid angioplasty and stenting (CAS)., Methods: We prospectively recruited participants with carotid stenosis ≥80% undergoing CAS at our institute between October 2019 and March 2023. Magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), and the Mini-Mental State Examination (MMSE) were performed 3 days before CAS. MRI with DTI and MMSE were conducted within 24 hours and 2 months after CAS, respectively. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was calculated from the DTI data to determine the ISF status. Increments were defined as the ratio of the difference between post- and preprocedural values to preprocedural values., Results: In total, 102 participants (age: 67.1±8.9 years; stenosis: 89.5%±5.7%) with longitudinal data were evaluated. The DTI-ALPS index increased after CAS (0.85±0.15; 0.85 [0.22] vs. 0.86±0.14; 0.86 [0.21]; P=0.022), as did the MMSE score (25.9±3.7; 24.0 [4.0] vs. 26.9±3.4; 26.0 [3.0]; P<0.001). Positive correlations between increments in the DTI-ALPS index and MMSE score were found in all patients (rs=0.468; P<0.001)., Conclusion: An increased 24-hour post-CAS DTI-ALPS index suggests early improvement in ISF flow efficiency. The positive correlation between the 24-hour DTI-ALPS index and 2-month MMSE score increments suggests that early ISF flow improvement may contribute to long-term cognitive improvement after CAS.

Objective: To compare the real-world effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients., Methods: This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult-to-treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS)., Results: The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (-13.0 vs. -8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (-13.0 vs. -9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication-overuse headache (MOH) (-13.3 vs. -9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (-42.2 vs. -11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs., Conclusions: In this multicenter, real-world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

The circadian clock is the inner rhythm of life activities and is controlled by a self-sustained and endogenous molecular clock, which maintains a ~ 24 h internal oscillation. As the core element of the circadian clock, BMAL1 is susceptible to degradation through the ubiquitin-proteasome system (UPS). Nevertheless, scant information is available regarding the UPS enzymes that intricately modulate both the stability and transcriptional activity of BMAL1, affecting the cellular circadian rhythm. In this work, we identify and validate UBR5 as a new E3 ubiquitin ligase that interacts with BMAL1 by using affinity purification, mass spectrometry, and biochemical experiments. UBR5 overexpression induced BMAL1 ubiquitination, leading to diminished stability and reduced protein level of BMAL1, thereby attenuating its transcriptional activity. Consistent with this, UBR5 knockdown increases the BMAL1 protein. Domain mapping discloses that the C-terminus of BMAL1 interacts with the N-terminal domains of UBR5. Similarly, cell-line-based experiments discover that HYD, the UBR5 homolog in Drosophila, could interact with and downregulate CYCLE, the BMAL1 homolog in Drosophila. PER2-luciferase bioluminescence real-time reporting assay in a mammalian cell line and behavioral experiments in Drosophila reveal that UBR5 or hyd knockdown significantly reduces the period of the circadian clock. Therefore, our work discovers a new ubiquitin ligase UBR5 that regulates BMAL1 stability and circadian rhythm and elucidates the underlying molecular mechanism. This work provides an additional layer of complexity to the regulatory network of the circadian clock at the post-translational modification level, offering potential insights into the modulation of the dysregulated circadian rhythm., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

The contributing genetic factors of vertigo remain poorly characterized, particularly in individuals of non-European ancestries. Here we show the genetic landscape of vertigo in an Asian population-based cohort. In a two-stage genome-wide association study (N case = 6199; N control  = 54,587), we identify vertigo-associated genomic loci in DROSHA and ZNF91/LINC01224, with the latter replicating the findings in European ancestries. Gene-based association testing corroborates these findings. Interestingly, both genes are enriched in cerebellum, a key structure receiving sensory input from the vestibular system. Subjects carrying risk alleles from lead SNPs of DROSHA and ZNF91 incur a 1.74-fold risk of vertigo than those without. Moreover, composite clinical-polygenic risk scores allow differentiation between patients and controls, yielding an area under receiver operating characteristic curve of 0.69. This study identified novel genomic loci for vertigo in an Asian population-based cohort, which may help identifying high risk subjects and provide mechanistic insight in understanding the pathogenesis of vertigo., (© 2024. The Author(s).)

Three new ent-kaurane diterpenoids, silvaticusins A-C (1-3), along with a new ent-kaurane dimer silvaticusin D (4) were isolated from the aerial parts of Isodon silvaticus. The structures of these new compounds were established mainly by comprehensive analysis of their NMR and MS data. The absolute configuration of compounds 1 and 4 were determined using a single-crystal X-ray diffraction and computational methods, respectively. Compounds 2 and 3 were found to exhibit remarkable cytotoxic effects against five human tumor cell lines (HL-60, A-549, SMMC-7721, MDA-MB-231, and SW-480), with IC 50 values spanning from 1.27 ± 0.08 to 7.52 ± 0.33 μM., (© 2024. The Author(s).)

When Fourier transform (FT) spectrum peaks are overlapped, primary maxima of odd-order derivatives can be used to evaluate their independent intensities. We studied the feasibility of higher odd-order derivatives on Lorentzian peak shape and magnitude peak shape. Simulation studies for FT nuclear magnetic resonance (NMR) spectroscopy demonstrated good results toward quantitative deconvolution of overlapping FT spectrum peaks. Although it is not so desirable to deconvolute special line shapes such as Gaussian, Voigt, and Tsallis profiles, the odd-order derivatives exhibit a bright future compared to even-order derivatives. An application example of practical NMR spectroscopy with ethylbenzene isomers is presented. White Gaussian noises were added to the simulated spectra at two different signal-to-noise ratios (20 and 40). Kauppinen's denoising and smoothing algorithms can effectively remove interference of the noise and help to have good deconvoluting results using the odd-order derivatives. We compared features of our approach with popular deconvolution sharpening algorithms and conducted a comparison study with Kauppinen's Fourier self-deconvolution. Our approach has a better dynamic range of peak intensities and is not sensitive to the sampling rates. Other common deconvolution methods are also discussed briefly., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: The demand for certified nurse aides (CNAs) in long-term care institutions is gradually increasing. Factors such as well-being that positively influence the work of CNAs have been inadequately explored in the literature., Purpose: This study was designed to examine the relationships among social support, self-efficacy, demographics, and psychological well-being in CNAs during the recent COVID-19 pandemic and to assess the moderating role of social support on self-efficacy and well-being in this population., Methods: In this quantitative correlational study, CNAs from 24 legally registered long-term care institutions were recruited as participants. Data were collected using a demographic questionnaire, the General Self-Efficacy Scale, the Social Support Scale, and the Chinese Happiness Inventory. Partial least squares structural equation modeling was used to test the research hypotheses model. The Strengthening the Reporting of Observational Studies in Epidemiology checklist was followed in this cross-sectional study., Results: A total of 148 CNAs were enrolled as participants. The mean age of the participants was 46.48 years. Social support and having children were identified as being significantly and positively correlated with well-being, and self-efficacy was identified as having no significant impact on well-being. Importantly, social support was found to moderate the relationship between self-efficacy and well-being. Overall, social support and having children were important predictors of well-being, with a combined explanatory power of 41.6% ( Q2 = .28, f2 = 0.40)., Conclusions/implications for Practice: Self-efficacy was found to be less predictive of well-being in the presence of higher levels of social support. Being a parent was also identified as an important factor affecting the well-being of CNAs under stress. Managers of long-term care institutions should intervene to improve the CNA's social support. Also, CNAs who do not have children should pay more attention to their well-being., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Objectives: Here, we report the distribution of HLA-DPB1 alleles studied in a cohort of 55 randomly collected blood samples from unrelated Taiwanese individuals and the deduced most likely HLA haplotypes associated with the defined DPB1 alleles in the cohort. Our aim is to reveal the unprecedented data on the distribution of HLA-DPB1 alleles in the Taiwanese population and to find out the most probable HLA haplotypes associated with the HLA-DPB1 alleles detected., Materials and Methods: The material for this study was blood samples, preserved in K 2 EDTA and/or acid citrate dextrose anticoagulants. The blood donors were voluntary individuals of Tzu Chi Bone Marrow Donor Registry, Tzu Chi Stem Cells Center, Hualien Tzu Chi Hospital. Sequence-based typing of the Sanger's sequencing method was performed for the HLA allelic typing. To discern the HLA-DPB1 alleles, exons 2 and 3 of the HLA-DPB1 locus were sequenced. Target exon sequence amplifications were achieved by polymerase chain reaction, and the resulting amplicons were sequenced by BigDye Terminator Cycle Sequencing Ready Reaction Kit according to the manufacturer's protocols., Results: In the total number of 55 randomized unrelated Taiwanese individuals studied, we detected 11 different HLA-DPB1 alleles. DPB1*05:01 (44.54%) was the allele with the highest frequency observed and the next highest frequency allele found was DPB1*02:01 (17.27%), while DPB1*38:01 (0.90%) and DPB1*700:01N (0.90%) ranked the least observed DPB1 alleles., Conclusion: Our findings in this study may be useful in researches reinforcing the comprehensive understanding on the distribution of DPB1 alleles and their associated HLA haplotypes and their clinical applications in Taiwanese., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Tzu Chi Medical Journal.)

Background: In bronchiectasis, nontuberculous mycobacteria (NTM) lung disease (NTM-LD) is a well-known coexisting infection. However, microorganism coisolates and clinical NTM-LD predictors are poorly studied., Methods: Patients with bronchiectasis diagnosed by means of computed tomography between January 2017 and June 2020 were screened, using the date of computed tomography as the index date. Those with a major bronchiectasis diagnosis in ≥2 follow-up visits after the index date were enrolled in the study, and NTM-LD occurrence and its association with pneumonia and hospitalization within 1 year were analyzed., Results: Of the 2717 participants, 79 (2.9%) had NTM-LD diagnosed. The factors associated with NTM-LD included hemoptysis, postinfectious bronchiectasis, a tree-in-bud score ≥2, a modified Reiff score ≥4, and chronic obstructive pulmonary disease (adjusted odds ratios, 1.80, 2.36, 1.78, 2.95, and 0.51, respectively). Compared with patients in the non-NTM group, those with NTM-LD had higher rates of hospitalization (15.9% vs 32.9%; P < .001) and pneumonia (9.8% vs 20.3%; P = .003). Pseudomonas aeruginosa was the most common microorganism in those with NTM-LD and those in the non-NTM group (10.1% vs 7.8%; P = .40). However, compared with those in the non-NTM group, Acinetobacter baumannii and Escherichia coli were more prevalent in patients with NTM-LD (0.7% vs 3.8% [ P = .03%] and 1.0% vs 3.8% [ P = .05], respectively)., Conclusions: Postinfectious bronchiectasis with hemoptysis, higher radiological involvement, and a tree-in-bud pattern were associated with NTM-LD risk. The rate of A baumannii and E coli coisolation was higher in bronchiectasis populations with NTM-LD., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Reversible cerebral vasoconstriction syndrome (RCVS) is a complex neurovascular disorder characterized by repetitive thunderclap headaches and reversible cerebral vasoconstriction. The pathophysiological mechanism of this mysterious syndrome remains underexplored and there is no clinically available molecular biomarker. To provide insight into the pathogenesis of RCVS, this study reported the first landscape of dysregulated proteome of cerebrospinal fluid (CSF) in patients with RCVS (n  =  21) compared to the age- and sex-matched controls (n  =  20) using data-independent acquisition mass spectrometry. Protein-protein interaction and functional enrichment analysis were employed to construct functional protein networks using the RCVS proteome. An RCVS-CSF proteome library resource of 1054 proteins was established, which illuminated large groups of upregulated proteins enriched in the brain and blood-brain barrier (BBB). Personalized RCVS-CSF proteomic profiles from 17 RCVS patients and 20 controls reveal proteomic changes involving the complement system, adhesion molecules, and extracellular matrix, which may contribute to the disruption of BBB and dysregulation of neurovascular units. Moreover, an additional validation cohort validated a panel of biomarker candidates and a two-protein signature predicted by machine learning model to discriminate RCVS patients from controls with an area under the curve of 0.997. This study reveals the first RCVS proteome and a potential pathogenetic mechanism of BBB and neurovascular unit dysfunction. It also nominates potential biomarker candidates that are mechanistically plausible for RCVS, which may offer potential diagnostic and therapeutic opportunities beyond the clinical manifestations., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Chlorpyrifos, widely used for pest control, is known to have various harmful effects, although its toxic effects in macrophages and the mechanisms underlying its toxicity remain unclear. The present study investigated the toxic effects of chlorypyrifos in a macrophage cell line. Here, we found that chlorpyrifos induced cytotoxicity and genotoxicity in RAW264.7 macrophages. Moreover, chlorpyrifos induced intracellular ROS production, subsequently leading to lipid peroxidation. Chlorpyrifos reduced the activation of antioxidative enzymes including superoxide dismutase, catalase, and glutathione peroxidase. Chlorpyrifos upregulated HO-1 expression and activated the Keap1-Nrf2 pathway, as indicated by enhanced Nrf2 phosphorylation and Keap1 degradation. Chlorpyrifos exerted effects on the following in a dose-dependent manner: cytotoxicity, genotoxicity, lipid peroxidation, intracellular ROS production, antioxidative enzyme activity reduction, HO-1 expression, Nrf2 phosphorylation, and Keap1 degradation. Notably, N-acetyl-L-cysteine successfully inhibited chlorpyrifos-induced intracellular ROS generation, cytotoxicity, and genotoxicity. Thus, chlorpyrifos may induce cytotoxicity and genotoxicity by promoting intracellular ROS production and suppressing the antioxidative defense system activation in macrophages., 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. Published by Elsevier B.V.)

Background: Our study aimed to confirm a simplified radiological scoring system, derived from a modified Reiff score, to evaluate its relationship with clinical symptoms and predictive outcomes in Taiwanese patients with noncystic fibrosis bronchiectasis (NCFB)., Methods: This extensive multicenter retrospective study, performed in Taiwan, concentrated on patients diagnosed with NCFB verified through high-resolution computed tomography (HRCT) scans. We not only compared the clinical features of various types of bronchiectasis (cylindrical, varicose, and cystic). Furthermore, we established relationships between the severity of clinical factors, including symptom scores, pulmonary function, pseudomonas aeruginosa colonization, exacerbation and admission rates, and HRCT parameters using modified Reiff scores., Results: Data from 2,753 patients were classified based on HRCT patterns (cylindrical, varicose, and cystic) and severity, assessed by modified Reiff scores (mild, moderate, and severe). With increasing HRCT severity, a significant correlation was found with decreased forced expiratory volume in the first second (FEV1) (p < 0.001), heightened clinical symptoms (p < 0.001), elevated pathogen colonization (pseudomonas aeruginosa) (p < 0.001), and an increased annual hospitalization rate (p < 0.001). In the following multivariate analysis, elderly age, pseudomonas aeruginosa pneumonia, and hospitalizations per year emerged as the only independent predictors of mortality., Conclusion: Based on our large cohort study, the simplified CT scoring system (Reiff score) can serve as a useful adjunct to clinical factors in predicting disease severity and prognosis among Taiwanese patients with NCFB., (© 2024. The Author(s).)

In pursuit of enhancing the mechanical properties, especially the tensile strength, of 4D-printable consumables derived from waste cooking oil (WCO), we initiated the production of acrylate-modified WCO, which encompasses epoxy waste oil methacrylate (EWOMA) and epoxy waste oil acrylate (EWOA). Subsequently, a series of WCO-based 4D-printable photocurable resins were obtained by introducing a suitable diacrylate molecule as the second monomer, coupled with a composite photoinitiator system comprising Irgacure 819 and p-dimethylaminobenzaldehyde (DMAB). These materials were amenable to molding using an LCD light-curing 3D printer. Our findings underscored the pivotal role of triethylene glycol dimethacrylate (TEGDMA) among the array of diacrylate molecules in enhancing the mechanical properties of WCO-based 4D-printable resins. Notably, the 4D-printable material, composed of EWOA and TEGDMA in an equal mass ratio, exhibited nice mechanical strength comparable to that of mainstream petroleum-based 4D-printable materials, boasting a tensile strength of 9.17 MPa and an elongation at break of 15.39%. These figures significantly outperformed the mechanical characteristics of pure EWOA or TEGDMA resins. Furthermore, the EWOA-TEGDMA resin demonstrated impressive thermally induced shape memory performance, enabling deformation and recovery at room temperature and retaining its shape at -60 °C. This resin also demonstrated favorable biodegradability, with an 8.34% weight loss after 45 days of soil degradation. As a result, this 4D-printable photocurable resin derived from WCO holds immense potential for the creation of a wide spectrum of high-performance intelligent devices, brackets, mold, folding structures, and personalized products.

Background: Mesenchymal stem cells (MSCs) have promising potential in clinical application, whereas their limited amount and sources hinder their bioavailability. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have become prominent options in regenerative medicine as both possess the ability to differentiate into MSCs., Methods: Recently, our research team has successfully developed human leukocyte antigen (HLA)-homozygous iPSC cell lines with high immune compatibility, covering 13.5% of the Taiwanese population. As we deepen our understanding of the differences between these ESCs and HLA-homozygous iPSCs, our study focused on morphological observations and flow cytometry analysis of specific surface marker proteins during the differentiation of ESCs and iPSCs into MSCs., Results: The results showed no significant differences between the two pluripotent stem cells, and both of them demonstrated the equivalent ability to further differentiate into adipose, cartilage, and bone cells., Conclusion: Our research revealed that these iPSCs with high immune compatibility exhibit the same differentiation potential as ESCs, enhancing the future applicability of highly immune-compatible iPSCs., Competing Interests: Conflicts of interest: Dr. Shih-Hwa Chiou, an editorial board member at Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. The other 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.)

Background: We aimed to redefine Immune checkpoint inhibitors (ICIs)-responsive "hot" TME and develop a corresponding stratification model to maximize ICIs-efficacy in Hepatocellular Carcinoma (HCC)., Methods: Hypoxic scores were designed, and the relevance to immunotherapy responses were validated in pan-cancers through single cell analysis. Multi-omics analysis using the hypoxic scores and immune infiltrate abundance was performed to redefine the ICIs-responsive TME subtype in HCC patients from TCGA (n = 363) and HCCDB database (n = 228). The immune hypoxic stress index (IHSI) was constructed to stratify the ICIs-responsive TME subtype, with exploring biological mechanism in vitro and in vivo. MRI-radiomics models were built for clinical applicability., Results: The hypoxic scores were lower in the dominant cell-subclusters of responders in pan-cancers. The higher immune infiltrate-normoxic (HIN) subtype was redefined as the ICIs-responsive TME. Stratification of the HIN subtype using IHSI effectively identified ICIs-responders in Melanoma (n = 122) and urological cancer (n = 22). TRAF3IP3, the constituent gene of IHSI, was implicated in ICIs-relevant "immune-hypoxic" crosstalk by stimulating MAVS/IFN-I pathway under normoxic condition. MRI-radiomics models assessing TRAF3IP3 with HIF1A expression (AUC > 0.80) screened ICIs-Responders in HCC cohort (n = 75)., Conclusion: The hypoxic-immune stratification redefined ICIs-responsive TME and provided MRI-Radiomics models for initial ICIs-responders screening, with IHSI facilitating further identification., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Utilising both morphological and molecular analyses, this study unveils Mazusjiangshiense sp. nov. , a novel addition to the Mazaceae family, discovered in Shaowu County, Fujian Province, China. The comprehensive description and illustrations provided here are a result of a meticulous exploration of its morphological features. While bearing a resemblance to M.gracilis , this new-found species is distinguished by three distinct characteristics: its stems are delicately soft, its leaves possess a membranous quality and the ovary is notably villous at the apex. Integration of molecular evidence, derived from the nuclear ribosomal DNA (nrITS) and three plastid DNA sequences ( rps16 , rbcL and trnL-trnF ), unequivocally supports the classification of M.jiangshiense as a distinct species. Notably, the molecular analysis positions it as a sister species to M.spicatus , underscoring the phylogenetic relationships within the genus Mazus . Our research not only introduces M.jiangshiense as a novel taxonomic entity, but also provides a nuanced understanding of its morphological differences and molecular affinities, enriching our comprehension of the diversity and evolutionary relationships of Mazaceae., Competing Interests: The authors have declared that no competing interests exist., (Yong-Bin Chen, Xin-Yan Chen, Liang Ma, Zhuang Zhao, Shi-Pin Chen.)

Objective: Quantitative sensory testing is widely used in clinical and research settings to assess the sensory functions of healthy subjects and patients. It is of importance to establish normative values in a healthy population to provide reference for studies involving patients. Given the absence of normative values for pain thresholds in Taiwan, the aim of this study was to report the normative values for future reference in the Taiwanese population and compare the differences between male and female participants., Methods: Healthy adults without any chronic or acute pain condition were recruited. The pain thresholds were assessed over the cephalic (supraorbital area and masseter muscle) and extracephalic (medio-volar forearm and thenar eminence) areas. The heat, cold, mechanical punctate, and pressure pain thresholds were measured with a standardized protocol. Comparisons between male and female participants were performed., Results: One hundred and thirty healthy participants (55 males: 30.4 ± 7.4 years; 75 females: 30.5 ± 8.1 years) finished the assessments. Male participants were less sensitive to mechanical stimuli, including pressure over masseter muscle (male vs. female: 178.5 ± 56.7 vs. 156.6 ± 58.4 kPa, p = .034) and punctate over medio-volar forearm (male vs. female: 116.4 ± 45.2 vs. 98.7 ± 65.4 g, p = .011), compared to female participants. However, female participants were less sensitive to cold stimuli, indicated by lower cold pain thresholds over the supraorbital area (male vs. female: 18.6 ± 8.4 vs. 13.6 ± 9.3°C, p = .004), compared to male participants. No significant differences were found between sexes in other pain threshold parameters., Conclusions: We provided the normative values of healthy male and female adults in Taiwan. This information is crucial for comparison in future pain-related studies to identify potential hypoalgesia or hyperalgesia of tested subjects., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Chronic migraine (CM) is a profoundly debilitating condition that has detrimental clinical and social outcomes. Over the past two decades, novel small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists, known as gepants, and CGRP monoclonal antibodies (mAbs) have been developed, ushering in a new era of migraine-specific treatment. In this review, we discuss the literature investigating the role of gepants for the treatment of CM. Numerous completed and ongoing clinical studies have conclusively demonstrated the safety, tolerability, and efficacy of several gepants for the acute treatment of migraine. However, preventive trials involving gepants have focused on patients with episodic migraine, with atogepant being the only gepant approved for CM prevention by the US Food and Drug Administration at the time of writing. Although some preliminary positive results have been reported, further research is still required to achieve additional advancements in the future. In summary, the effectiveness of gepants for treating individuals with CM are highly expected. This review highlights the development and current progress of gepants for the treatment of CM, focusing both on their role as acute abortive agents and preventive measures and on their concomitant use with other antimigraine medications, such as CGRP mAbs or triptans., 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.)

Physical exercise is crucial to the development of students' physical and mental health. This study explored the relationship between live sports learning and college students' exercise behaviors, and the mediating roles of exercise motivation and exercise commitment, aiming to provide theoretical bases for the future that explain the mechanism of live sports learning in exercise behaviors, as well as practical guidance for the promotion of positive physical exercise behaviors in college students. In total, 1189 college students from China volunteered to complete questionnaires. The results showed that live sports learning positively predicted college students' exercise behavior and that live sports learning was able to affect exercise behavior through the mediating roles of exercise motivation and exercise commitment, with specific mediating paths including the two independent mediating paths and a serial mediating path of exercise motivation and exercise commitment. This study confirmed, for the first time, on live sports learning in the process of promoting exercise behavior. It is suggested that educators instruct college students to regulate their participation in live sports learning and to cultivate healthy exercise motivation and exercise commitment, which is an effective way to facilitate college students' practice of physical activity.

The Tripterospermum , comprising 34 species, is a genus of Gentianaceae. Members of Tripterospermum are mostly perennial, entwined herbs with high medicinal value and rich in iridoids, xanthones, flavonoids, and triterpenes. However, our inadequate understanding of the differences in the plastid genome sequences of Tripterospermum species has severely hindered the study of their evolution and phylogeny. Therefore, we first analyzed the 86 Gentianae plastid genomes to explore the phylogenetic relationships within the Gentianae subfamily where Tripterospermum is located. Then, we analyzed six plastid genomes of Tripterospermum , including two newly sequenced plastid genomes and four previously published plastid genomes, to explore the plastid genomes' evolution and phylogenetic relationships in the genus Tripterospermum . The Tripterospermum plastomes have a quadripartite structure and are between 150,929 and 151,350 bp in size. The plastomes of Tripterospermum encoding 134 genes were detected, including 86 protein-coding genes (CDS), 37 transfer RNA (tRNA) genes, eight ribosomal RNA (rRNA) genes, and three pseudogenes ( infA , rps19 , and ycf1 ). The result of the comparison shows that the Tripterospermum plastomes are very conserved, with the total plastome GC content ranging from 37.70% to 37.79%. In repeat sequence analysis, the number of single nucleotide repeats (A/T) varies among the six Tripterospermum species, and the identified main long repeat types are forward and palindromic repeats. The degree of conservation is higher at the SC/IR boundary. The regions with the highest divergence in the CDS and the intergenic region (IGS) are psaI and rrn4.5-rrn5 , respectively. The average pi of the CDS and the IGS are only 0.071% and 0.232%, respectively, indicating that the Tripterospermum plastomes are highly conserved. Phylogenetic analysis indicated that Gentianinae is divided into two clades, with Tripterospermum as a sister to Sinogeniana . Phylogenetic trees based on CDS and CDS + IGS combined matrices have strong support in Tripterospermum . These findings contribute to the elucidation of the plastid genome evolution of Tripterospermum and provide a foundation for further exploration and resource utilization within this genus.

Background: Patients with bipolar disorder (BD) receive traditional Chinese medicine (TCM) for clinical needs unmet with psychotropic medications. However, the clinical characteristics of practices and outcomes of TCM in BD are not fully understood. This cohort study investigated the clinical characteristics, principal diagnoses, TCM interventions, and TCM prescriptions in patients with BD., Methods: Data for a total of 12,113 patients with BD between 1996 and 2013 were withdrawn from Taiwan's longitudinal health insurance database 2000 (LHID 2000). The chi-square test was used for categorical variables, and the independent t -test was used for continuous variables. A p -value less than 0.05 indicated significance., Results: One thousand three hundred nineteen patients who visited TCM clinics after the diagnosis of BD were in the TCM group, while those who never visited TCM were in the non-TCM group ( n = 1053). Compared to the non-TCM group, patients in the TCM group had younger average age, a higher percentage of female individuals, more comorbidities of anxiety and alcohol use disorders, and higher mood stabilizer usage rates. The TCM group exhibited pain-related indications, including joint pain, myalgia, myositis, headache, and sleep disturbances. Corydalis yanhusuo and Shu-Jing-Huo-Xue-Tang were the most useful single herbs and herbal formulae., Conclusions: Physicians need to be aware of the use of TCM in patients with BD.

Background: The pathophysiology of the reversible cerebral vasoconstriction syndrome (RCVS) remains enigmatic and the role of glymphatics in RCVS pathophysiology has not been evaluated. We aimed to investigate RCVS glymphatic dynamics and its clinical correlates., Methods: We prospectively evaluated the glymphatic function in RCVS patients, with RCVS subjects and healthy controls (HCs) recruited between August 2020 and November 2023, by calculating diffusion-tensor imaging along the perivascular space (DTI-ALPS) index under a 3-T MRI. Clinical and vascular (transcranial color-coded duplex sonography) investigations were conducted in RCVS subjects. RCVS participants were separated into acute (≤ 30 days) and remission (≥ 90 days) groups by disease onset to MRI interval. The time-trend, acute stage and longitudinal analyses of the DTI-ALPS index were conducted. Correlations between DTI-ALPS index and vascular and clinical parameters were performed. Bonferroni correction was applied to vascular investigations (q = 0.05/11)., Results: A total of 138 RCVS patients (mean age, 46.8 years ± 11.8; 128 women) and 42 HCs (mean age, 46.0 years ± 4.5; 35 women) were evaluated. Acute RCVS demonstrated lower DTI-ALPS index than HCs (p < 0.001) and remission RCVS (p < 0.001). A continuously increasing DTI-ALPS trend after disease onset was demonstrated. The DTI-ALPS was lower when the internal carotid arteries resistance index and six-item Headache Impact test scores were higher. In contrast, during 50-100 days after disease onset, the DTI-ALPS index was higher when the middle cerebral artery flow velocity was higher., Conclusions: Glymphatic function in patients with RCVS exhibited a unique dynamic evolution that was temporally coupled to different vascular indices and headache-related disabilities along the disease course. These findings may provide novel insights into the complex interactions between glymphatic transport, vasomotor control and pain modulation., (© 2024. The Author(s).)

Ribonucleic acid therapeutics have advantages over biologics and small molecules, including lower safety risks, cheaper costs, and extensive targeting flexibility, which is rapidly fueling the expansion of the field. This is made possible by breakthroughs in the field of drug delivery, wherein lipid nanoparticles (LNPs) are one of the most clinically advanced systems. LNP formulations that are currently approved for clinical use typically contain an ionizable cationic lipid, a phospholipid, cholesterol, and a polyethylene glycol-lipid; each contributes to the stability and/or effectiveness of LNPs. In this review, we discuss the immunomodulatory effects associated with each of the lipid components. We highlight several studies in which the components of LNPs have been implicated in cellular sensing and explore the pathways involved., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: AKB is a cofounder of VaxEquity, a company that develops self-amplifying RNA vaccines., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: This study, conducted in October 2017 at two Canadian universities, aimed to explore the relationships between gender expression, protective coping strategies, alcohol saliency, and high-risk alcohol use., Methods: Validated scales were employed to assess these variables using survey data. Multivariate analyses were conducted to investigate the associations between these factors and high-risk drinking., Results: This study revealed significant associations between high-risk drinking and androgynous gender roles (OR = 1.58, 95% CI: 1.19-2.10) as well as among self-reported males (OR = 2.21; 95% CI: 1.77-2.75). Additionally, protective behavioural strategies were inversely related to high-risk drinking (OR = 0.95; 95% CI: 0.94-0.96), while higher alcohol saliency exhibited a positive correlation with high-risk drinking (OR = 1.12; 95% CI: 1.11-1.14)., Conclusions: These findings underscore the importance of considering gender, alcohol saliency beliefs, and protective behavioural strategies in the development and refinement of interventions aimed at reducing high-risk alcohol use on Canadian campuses.

Background: Half of the sufferers of reversible cerebral vasoconstriction syndrome (RCVS) exhibit imaging-proven blood-brain barrier disruption. The pathogenesis of blood-brain barrier disruption in RCVS remains unclear and mechanism-specific intervention is lacking. We speculated that cerebrovascular dysregulation might be associated with blood-brain barrier disruption in RCVS. Hence, we aimed to evaluate whether the dynamic cerebral autoregulation is altered in patients with RCVS and could be associated with blood-brain barrier disruption., Methods: A cross-sectional study was conducted from 2019 to 2021 at headache clinics of a national tertiary medical center. Dynamic cerebral autoregulation was evaluated in all participants. The capacity of the dynamic cerebral autoregulation to damp the systemic hemodynamic changes, i.e., phase shift and gain between the cerebral blood flow and blood pressure waveforms in the very-low- and low-frequency bands were calculated by transfer function analysis. The mean flow correlation index was also calculated. Patients with RCVS received 3-dimensional isotropic contrast-enhanced T2 fluid-attenuated inversion recovery imaging to visualize blood-brain barrier disruption., Results: Forty-five patients with RCVS (41.9 ± 9.8 years old, 29 females) and 45 matched healthy controls (41.4 ± 12.5 years old, 29 females) completed the study. Nineteen of the patients had blood-brain barrier disruption. Compared to healthy controls, patients with RCVS had poorer dynamic cerebral autoregulation, indicated by higher gain in very-low-frequency band (left: 1.6 ± 0.7, p = 0.001; right: 1.5 ± 0.7, p = 0.003; healthy controls: 1.1 ± 0.4) and higher mean flow correlation index (left: 0.39 ± 0.20, p = 0.040; right: 0.40 ± 0.18, p = 0.017; healthy controls: 0.31 ± 0.17). Moreover, patients with RCVS with blood-brain barrier disruption had worse dynamic cerebral autoregulation, as compared to those without blood-brain barrier disruption, by having less phase shift in very-low- and low-frequency bands, and higher mean flow correlation index., Conclusions: Dysfunctional dynamic cerebral autoregulation was observed in patients with RCVS, particularly in those with blood-brain barrier disruption. These findings suggest that impaired cerebral autoregulation plays a pivotal role in RCVS pathophysiology and may be relevant to complications associated with blood-brain barrier disruption by impaired capacity of maintaining stable cerebral blood flow under fluctuating blood pressure., (© 2023. The Author(s).)

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy, caused by cysteine-altering variants in NOTCH3 , is the most prevalent inherited cerebral small vessel disease. Impaired cerebral interstitial fluid dynamics has been proposed as one of the potential culprits of neurodegeneration and may play a critical role in the initiation and progression of cerebral small vessel disease. In the present study, we aimed to explore the cerebral interstitial fluid dynamics in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy and to evaluate its association with clinical features, imaging biomarkers and disease severity of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy. Eighty-one participants carrying a cysteine-altering variant in NOTCH3 , including 44 symptomatic cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy patients and 37 preclinical carriers, and 21 age- and sex-matched healthy control individuals were recruited. All participants underwent brain MRI studies and neuropsychological evaluations. Cerebral interstitial fluid dynamics was investigated by using the non-invasive diffusion tensor image analysis along the perivascular space method. We found that cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy patients exhibited significantly lower values of diffusion tensor image analysis along the perivascular space index comparing to preclinical carriers and healthy controls. For the 81 subjects carrying NOTCH3 variants, older age and presence of hypertension were independently associated with decreased diffusion tensor image analysis along the perivascular space index. The degree of cerebral interstitial fluid dynamics was strongly related to the severity of cerebral small vessel disease imaging markers, with a positive correlation between diffusion tensor image analysis along the perivascular space index and brain parenchymal fraction and negative correlations between diffusion tensor image analysis along the perivascular space index and total volume of white matter hyperintensity, peak width of skeletonized mean diffusivity, lacune numbers and cerebral microbleed counts. In addition, diffusion tensor image analysis along the perivascular space index was a significant risk factor associated with the development of clinical symptoms of stroke or cognitive dysfunction in individuals carrying NOTCH3 variants. In cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy patients, diffusion tensor image analysis along the perivascular space index was significantly associated with Mini-Mental State Examination scores. Mediation analysis showed that compromised cerebral interstitial fluid dynamics was not only directly associated with cognitive dysfunction but also had an indirect effect on cognition by influencing brain atrophy, white matter disruption, lacunar lesions and cerebral microbleeds. In conclusion, cerebral interstitial fluid dynamics is impaired in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy and its disruption may play an important role in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy. Diffusion tensor image analysis along the perivascular space index may serve as a biomarker of disease severity for cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Understanding of Long COVID has advanced through patient-led initiatives. However, research about barriers to accessing Long COVID services is limited. This study aimed to better understand the need for, access to, and quality of, Long COVID services. We explored health needs and experiences of services, including ability of services to address needs., Methods: Our study was informed by the Levesque et al.'s (2013) "conceptual framework of access to health care." We used Interpretive Description, a qualitative approach partly aimed at informing clinical decisions. We recruited participants across five settings. Participants engaged in one-time, semi-structured, virtual interviews. Interviews were transcribed verbatim. We used reflexive thematic analysis. Best practice to ensure methodological rigour was employed., Results: Three key themes were generated from 56 interviews. The first theme illustrated the rollercoaster-like nature of participants' Long COVID symptoms and the resulting impact on function and health. The second theme highlighted participants' attempts to access Long COVID services. Guidance received from healthcare professionals and self-advocacy impacted initial access. When navigating Long COVID services within the broader system, participants encountered barriers to access around stigma; appointment logistics; testing and 'normal' results; and financial precarity and affordability of services. The third theme illuminated common factors participants liked and disliked about Long COVID services. We framed each sub-theme as the key lesson (stemming from all likes and dislikes) that, if acted upon, the health system can use to improve the quality of Long COVID services. This provides tangible ways to improve the system based directly on what we heard from participants., Conclusion: With Long COVID services continuously evolving, our findings can inform decision makers within the health system to better understand the lived experiences of Long COVID and tailor services and policies appropriately., (© 2023. The Author(s).)

The present study examined the relationship between physical exercise and social anxiety by testing a moderated mediation model that focused on how peer relationships mediate the relationship between physical exercise and social anxiety and how flow experience moderates this mediated relationship. A total of 1056 middle school students from six middle schools in Sichuan, China, volunteered to complete questionnaires comprising the Physical Activity Rating Scale, Student Peer Relationship Scale, Social Anxiety Subscale of the Self-Consciousness Scale, and Short (9-Item) Dispositional Flow Scales. Regression analysis indicated that physical exercise negatively influenced social anxiety through peer relationships (indirect effect = -0.04, 95% CI = [-0.067, -0.013]). In addition, a moderated regression analysis indicated that under high-flow experience, physical exercise suppresses social anxiety through positive effects on peer relationships (indirect effect = -0.04, 95% CI = [-0.087, -0.003]), and under low-flow experience, physical exercise exacerbates social anxiety through negative effects on peer relationships (indirect effect = 0.06, 95% CI = [0.016, 0.105]). Some practical implications have been discussed on the physical exercise intervention for suppressing social anxiety in middle school students., (© 2023. The Author(s).)

Introduction: Reversible cerebral vasoconstriction syndrome (RCVS) is a rare, but increasingly recognised cerebrovascular condition with an estimated annual age-standardised incidence of approximately three cases per million. Knowledge about risk factors and triggering conditions and information about prognosis and optimal treatment in these patients are limited., Methods: The REversible cerebral Vasoconstriction syndrome intERnational CollaborativE (REVERCE) project aims to elucidate the epidemiological and clinical characteristics of RCVS by collecting individual patient data from four countries (France, Italy, Taiwan and South Korea) in the setting of a multicentric study. All patients with a diagnosis of definite RCVS will be included. Data on the distribution of risk factors and triggering conditions, imaging data, neurological complications, functional outcome, risk of recurrent vascular events and death and finally the use of specific treatments will be collected. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and geographical region of residence., Ethics and Dissemination: Ethical approval for the REVERCE study will be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of clinical and epidemiological characteristics of RCVS patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors do not have any conflicts of interest related to the submitted work. KSL reports personal fees (Teva, Acticor Biotech). JM reports personal fees (Abbvie, GEP Sante, Lundbeck, Homeperf, Teva, Lilly, Lundbeck, Pfizer). MJL reports personal fees (Eli Lilly, Lundbeck, Pfizer, NuEyne Co., Teva, Abbvie, SK chemical, CKD Pharm, YuYu Pharma), research grants (Eli Lilly, Otsuka, Novartis, Allergan, BioHaven, Lundbeck, Eli Lilly/Ildong), and funding Seoul National University New Faculty Startup Fund, National Research Foundation of Korea grant funded by the Korea Government (MSIP) Yuhan company). AD reports personal fees (Allergan Abbvie, Lilly, Teva, Lundbeck, Pfizer, SOS). SJW reports personal fees (AbbVie, Pfizer, Eli Lilly, Biogen), research grants (Eli Lilly, Novartis) and has been principal investigator in sponsored trials (Novartis, Lundbeck and Orient Europharma). The other authors have nothing to disclose.