Search

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: Aconite poisoning is a severe, life-threatening poisoning related to the use of traditional Chinese medicine (TCM). Despite current legislation, repeated poisoning cases are steadily encountered.Objective: The aim of the study was to summarize the clinical features and to elucidate the causative and contributory factors leading to aconite poisoning.Methods: This study was conducted within the Hospital Authority Toxicology Reference Laboratory, which is the sole tertiary referral clinical toxicology laboratory in Hong Kong. This retrospective study reviewed all confirmed aconite poisoning cases handled by a clinical toxicology laboratory between April 2004 and July 2009. The diagnosis in all cases was confirmed biochemically by detecting aconitum alkaloids in urine specimens. Additionally, herbal specimens were morphologically identified and herbal formulae were studied and transcribed. The cause of poisoning for each case was determined whenever possible.Results: Fifty-two cases were examined in this aconite poisoning case series. Neurological, cardiovascular and gastrointestinal toxicities were encountered in 49 (94.2%), 46 (88.5%) and 31 (59.6%) patients, respectively. The poisoning was severe in 6 (11.5%) patients, moderate in 17 (32.7%) patients and mild in 29 (55.8%) patients. Amongst 44 patients (84.6%) in whom the underlying reasons of poisoning could be determined, four major causes were found. These included overdose - prescription of a higher than recommended dosage of aconite herbs in 17 (32.7%) cases; 'hidden' poisoning (the aconite herb was not prescribed but dispensed inadvertently) in 17 (32.7%) cases; usage of inadequately processed herbs in 7 (13.5%) cases; and dispensary error in 2 (3.9%) cases. No case fatality was recorded.Conclusion: In the majority of cases in this series, the causes of poisoning can be traced to poor-quality herbs, poor quality of prescription practice, or dispensary errors. The quality issues of TCM practice should be critically addressed to minimize this poisoning threat. [ABSTRACT FROM AUTHOR]

Renal-cell carcinoma (RCC) is susceptible to immune therapy including the use of the nonmyeloablative allogeneic transplantation (NST). However, NST can produce severe toxicity, might not be appropriate for many patients with metastatic RCC. Other novel allogeneic immunotherapies are designed to induce an autologous immune response directed against the malignancy. In single-arm phase II trials, thalidomide has demonstrated a modest activity in the treatment of advanced RCC. Here we present a case report in which a patient with advanced RCC in the absence of transplant conditioning, that was receiving thalidomide, was infused with partially HLA-matched irradiated allogeneic lymphocytes. In this patient a complete response with weak acute graft-versus-host disease (GVHD) was observed. No evidence of the disease was present over the subsequent 36 months survival of the patient, suggesting that the infusions may have played a major role in the antineoplastic effect. A potential mechanism of this protocol may involve a host-versus-graft reactions-mediated antitumor effect against the malignancy. In addition, the present results suggest that a combination protocol with alternate treatment (e.g., chemotherapy) schedules merit further investigation in the management of various malignancies. [ABSTRACT FROM AUTHOR]

The purpose of this retrospective study was to describe the magnitude, nature, and costs of assault injuries among teachers, a high-risk group. Review of assault cases (N = 341) was based on internal and case management vendor records. The 3-year assault rate was 3.24 per 1,000 teachers. Assaults were predominately physical, occurring during classroom disputes and while restraining students. Assaults accounted for 2,480 lost workdays and more than $714,000 in lost wages and case management fees. The most costly injuries on a per-case basis were strain-sprain injuries resulting in lost workdays and fractures not resulting in lost workdays. Less than 20% of the assaults accounted for all of the lost workdays and most of the case costs. Study variables accounted for 13% of case costs. Occupational health nurses should collaborate with school personnel, administrators, and parents to develop prevention programs, which may include de-escalation techniques for teachers as well as case management strategies. [ABSTRACT FROM AUTHOR]

Key Message: Approaches for constructing training sets in genomic selection are proposed to efficiently identify top-performing genotypes from a breeding population. Identifying superior genotypes from a candidate population is a key objective in plant breeding programs. This study evaluates various methods for the training set optimization in genomic selection, with the goal of enhancing efficiency in discovering top-performing genotypes from a breeding population. Additionally, two approaches, inspired by classical optimal design criteria, are proposed to expand the search space for the best genotypes and compared with methods focusing on maximizing accuracy in breeding value prediction. Evaluation metrics such as normalized discounted cumulative gain, Spearman's rank correlation, and Pearson's correlation are employed to assess performance in both simulation studies and real trait analyses. Overall, for candidate populations lacking a strong subpopulation structure, a ridge regression-based method, referred to as MSPE Ridge , is recommended. For candidate populations with a strong subpopulation structure, a heuristic-based version of generalized coefficient of determination CD mean ( v 2 ) and a D-optimality-like method that maximizes overall genomic variation ( GV overall ) are preferred approaches for the primary objective of plant breeding. For populations with a large number of candidates, a proposed ranking method ( GV average ) can first be used to down-scale the candidate population, after which a heuristic-based method is employed to identify the best genotypes. Notably, the proposed CD mean ( v 2 ) has been verified to be equivalent to the original version, known as CD mean , but its implementation is much more computationally efficient., Competing Interests: Declarations Conflict of interest The authors declare that there is no conflict of interest., (© 2024. The Author(s).)

Objective: To determine sex differences in clinical profiles and treatment outcomes in patients with spontaneous intracranial hypotension., Background: Spontaneous intracranial hypotension is associated with considerable functional disability and potentially fatal complications, and it is uncertain whether males and females should be managed differently., Methods: This was a cohort study of consecutive patients with spontaneous intracranial hypotension enrolled from a medical center. Medical records and imaging findings were reviewed. The outcome of treatment responses to epidural blood patches and risks of subdural hematoma were measured., Results: In total, 442 patients with spontaneous intracranial hypotension (165 males, 277 females) were included in the analysis. Males were more likely to have a delayed (>30 days) initial presentation than females (32.1% [53/165] vs. 19.9% [55/277], p = 0.004), and males were less likely to have nausea (55.8% [92/165] vs. 67.1% [186/277], p = 0.016), vomiting (43.0% [71/165] vs. 54.2% [150/277], p = 0.024), photophobia (9.7% [16/165] vs. 17.0% [47/277], p = 0.034), and tinnitus (26.7% [44/165] vs. 39.7% [110/277], p = 0.005) compared with females despite comparable radiologic findings. Among the 374 patients treated with epidural blood patches, males were more likely to be nonresponders to the first epidural blood patch (58.0% [80/138] vs. 39.0% [92/236], OR = 2.2, 95% CI = 1.4-3.3, p < 0.001). Males were at a higher risk of having subdural hematoma (29.7% [49/165] vs. 10.8% [30/277], OR = 3.5, 95% CI = 2.1-5.8, p < 0.001). Among patients with subdural hematoma, males had greater thickness (12.8 ± 4.3 vs. 8.1 ± 5.9 mm, p < 0.001) and were more likely to receive surgical drainage (55.1% [27/49] vs. 10.0% [3/30], OR = 11.0, 95% CI = 3.0-41.3, p < 0.001) than females., Conclusion: In the present study, spontaneous intracranial hypotension in males was characterized by a delayed presentation, poorer response to the first epidural blood patch, and a higher risk of subdural hematoma. Caution should be exercised in the management of males with spontaneous intracranial hypotension. The generalizability of the findings needs to be further confirmed., (© 2024 The Author(s). Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Objective. This study aimed to explore the mental health status, coping strategies, and social support of international students in Canada. Participants. Undergraduate and graduate international students studying at one Canadian university participated in an online survey. Methods. The survey consisting of four assessments-the Mental Health Continuum-Short Form, Kessler Psychological Distress Scale, the Carver Brief-Cope Inventory, and the Multidimensional Scale of Perceived Social Support-was distributed during the winter and spring terms of 2020. Results. Of the 338 participants from 53 countries, 76% demonstrated optimal mental health without mental disorders; 86% used approach coping strategies. Those who are women, married, and Ph.D. students showed better mental health and lower psychological distress. Coping skills and social support significantly predict participants' psychological distress and subjective well-being. Conclusions. This study findings address the gaps in meeting the mental health needs of international students and raise awareness of this population's unique mental health status.

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).)

Integrating structural colors and conductivity into aqueous inks has the potential to revolutionize wearable electronics, providing flexibility, sustainability, and artistic appeal to electronic components. This study aims to introduce bioinspired color engineering to conductive aqueous inks. Our self-assembly approach involves mixing poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) with sulfonic acid-modified polystyrene (sPS) colloids to generate non-iridescent structural colors in the inks. This spontaneous structural coloration occurs because PEDOT:PSS and sPS colloids can self-assemble into core-shell structures and reversibly cluster into photonic aggregates of maximally random jammed packing within the aqueous environment, as demonstrated by small-angle X-ray scattering. Dissipative particle dynamics simulation confirms that the self-assembly aggregation of PEDOT:PSS chains and sPS colloids can be manipulated by the polymer-colloid interactions. Utilizing the finite-difference time-domain method, we demonstrate that the photonic aggregates of the core-shell colloids achieve close to maximum jammed packing, making them suitable for producing vivid structural colors. These versatile conductive inks offer adjustable color saturation and conductivity, with conductivity levels reaching 36 S cm -1 through the addition of polyethylene glycol oligomer, while enhanced water resistance and mechanical stability are achieved by doping with a cross-linker, poly(ethylene glycol) diglycidyl ether. With these unique features, the inks can create flexible, patterned circuits through processes like coating, writing, and dyeing on large areas, providing eco-friendly, visually appealing colors for customizable, stylish, comfortable, and wearable electronic devices.

In 2020, the COVID-19 pandemic caused mandatory lockdowns worldwide, exacerbating mental health issues created by social isolation. Aimed to improve mental health and maintain engagement, the Singapore Art Museum (SAM) rapidly deployed an online programme called Unwind with SAM to engage the public with the museum's contemporary art collection coupled with meditation. The programme focused on the positive effect of arts on mental health, combined with the cognitive benefits of meditation by 'slow-looking' at artworks. This practice-based report reflects on the processes and explores the potential between art, contemplation and cognitive sciences. The first section outlines the current landscape of art and wellness approaches in museums. The second section explains the philosophical framework that guides the programme, alongside a breakdown of components and design rationale. The final part provides a critical reflection and concludes with recommendations for practitioners, managers and scientists to utilise the framework for designing future programmes.

Reverse electron transfer (RET), an abnormal backward flow of electrons from complexes III/IV to II/I of mitochondria, causes the overproduction of a reduced-type CoQ to boost downstream production of mitochondrial superoxide anions that leads to ischemia-reperfusion injury (IRI) to organs. Herein, we studied low-coordinated gold nanoclusters (AuNCs) with abundant oxygen-binding sites to form an electron-demanding trapper that allowed rapid capture of electrons to compensate for the CoQ/CoQH 2 imbalance during RET. The AuNCs were composed of only eight gold atoms that formed a Cs-symmetrical configuration with all gold atoms exposed on the edge site. The geometry and atomic configuration enhance oxygen intercalation to attain a d-band electron deficiency in frontier orbitals, forming an unusually high oxidation state for rapid mitochondrial reverse electron capture under a transient imbalance of CoQ/CoQH 2 redox cycles. Using hepatic IRI cells/animals, we corroborated that the CoQ-like AuNCs prevent inflammation and liver damage from IRI via recovery of the mitochondrial function.

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.

This study investigated the sex-specific associations between pain perception and testosterone levels in healthy controls (HCs) and patients with migraine. Male and female HCs and migraine patients were recruited. A series of questionnaires were completed by the participants to evaluate their psychosocial profiles, which included data on mood, stress, and sleep quality. Heat pain thresholds and suprathreshold pain ratings at 45 °C (referred to as the pain perception score [PPS]) were assessed using the Thermode system. Salivary testosterone levels were analyzed using a commercial enzyme-linked immunosorbent assay kit. A total of 88 HCs (men/women: 41/47, age: 29.9 ± 7.7 years) and 75 migraine patients (men/women: 30/45, age: 31.1 ± 7.7 years) completed all assessments. No significant differences were observed in either the psychosocial profiles or heat pain thresholds and PPSs between the sexes in the control and migraine groups. A positive correlation between testosterone levels and PPSs was identified in the male controls (r = .341, P = .029), whereas a negative correlation was identified in the female controls (r = -.407, P = .005). No such correlations were identified in the migraine group. This study confirms that a negative association is present between PPSs and testosterone levels in female controls, which is in line with the findings that testosterone is associated with reduced pain perception. Our study is the first to demonstrate a sex-specific association between PPSs and testosterone levels in HCs. Moreover, this study also revealed that the presence of migraine appears to disrupt this association. PERSPECTIVE: This study revealed that testosterone levels demonstrate opposite associations with pain perception in healthy men and women. However, the presence of migraine appears to disrupt this sex-specific association., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

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.)

Scoparodane C (1), a diterpenoid with a rare 3,4-seco-3-nor-2,11-epoxy-ent-clerodane scaffold, was obtained from the aerial parts of Isodon scoparius, along with isocopariusines A-E (2-6), five ent-clerodanoids featuring a 5/6-fused ring system, and isocopariusines F-H (7-9), three common ent-clerodanoids. The structures of these previously undescribed compounds were established by a combination of spectroscopic analysis, X-ray diffraction, chemical derivatization, and quantum chemical calculation. Remarkably, isocopariusine B (3) showed strong resistance reversal activity against fluconazole-resistant Candida albicans., 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 Elsevier Ltd. All rights reserved.)

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.)

The construction of the preferred orientation structure by stretching is an efficient strategy to fabricate high-performance cellulose film and it is still an open issue whether crystalline structure or amorphous molecular chain is the key factor in determining the enhanced mechanical performance. Herein, uniaxial stretching with constant width followed by drying in a stretching state was carried out to cellulose hydrogels with physical and chemical double cross-linking networks, achieving high-performance regenerated cellulose films (RCFs) with an impressive tensile strength of 154.5 MPa and an elastic modulus of 5.4 GPa. The hierarchical structure of RCFs during uniaxial stretching and drying was systematically characterized from micro- to nanoscale, including microscopic morphology, crystalline structure as well as relaxation behavior at a molecular level. The two-dimensional correlation spectra of dynamic mechanical analysis and Havriliak-Negami fitting results verified that the enhanced mechanical properties of RCFs were mainly attributed to the stretch-induced tight packing and restricted relaxation of amorphous molecular chains. The new insight concerning the contribution of molecular chains in the amorphous region to the enhancement of mechanical performance for RCFs is expected to provide valuable guidance for designing and fabricating high-performance eco-friendly cellulose-based films., 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 Elsevier Ltd. All rights reserved.)

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.)

Objective: To investigate the expression level of small nucleolar RNA (snoRNA) SNORA63 in bone marrow of patients with acute leukemia (AL) and its significance in the clinical diagnosis, treatment and prognosis of AL patients., Methods: Bone marrow samples of 53 newly diagnosed AL patients and 29 healthy subjects in the Affiliated Hospital of Guangdong Medical University from March 2018 to December 2021 were collected. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression level of SNORA63 in bone marrow mononuclear cells of the two groups. The median expression level of SNORA63 in AL patients was used as the boundary value to divide the patients into SNORA63 high and low expression groups, and the relationship between the expression level of SNORA63 and the clinical characteristics, clinical indicators and prognosis of AL patients was analyzed and discussed., Results: The relative expression level of SNORA63 in AL patients was significantly lower than that in healthy control group [0.3018 (0.0244-1.2792) vs 1.0882 (0.2797-1.9889)] ( P < 0.01). The expression level of SNORA63 in AL patients without remission after initial treatment was significantly lower than that in healthy controls and the patients who received complete remission (CR) ( P < 0.01), while there was no statistical difference in the expression level of SNORA63 between AML and ALL groups ( P >0.05). The abnormal low expression of SNORA63 was closely related to fever, hemorrage, poor prognosis, efficacy, platelets (PLT), lactate dehydrogenase (LDH), albumin (ALB), and molecular biological abnormalities of AL patients ( P < 0.05), but not significantly correlated with sex, age, AL subtype, pallor, fatigue, extramedullary infiltration, white blood cell count (WBC), hemoglobin (HGB), C-reactive protein (CRP), procalcitonin (PCT), fibrinogen (FIB) or chromosome karyotype ( P >0.05). Meanwhile, overall survival (OS) and event-free survival (EFS) of AL patients in SNORA63 high-expression group were significantly higher than those in SNORA63 low-expression group ( P < 0.05). Univariate Cox regression analysis showed that SNORA63 , molecular biological abnormalities, fever, PLT and LDH were the factors influencing OS and EFS in AL patients ( P < 0.05). Multivariate Cox regression analysis indicated that fever, molecular biological abnormalities and LDH were independent factors associated with OS and EFS in AL patients ( P < 0.05)., Conclusion: SNORA63 is significantly down-expressed in AL patients, which is a molecular marker of great clinical value for disease monitoring and prognosis evaluation in AL patients.

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.)

Purpose: To explore the relationship among resilience, stress, and demographic factors in certified nursing assistants (CNAs) who worked in long-term care institutions during the coronavirus disease 2019 pandemic., Method: A cross-sectional correlation-based research design was used. Data were collected using a demographic questionnaire, Connor-Davidson Resilience Scale, and Occupational Stress Scale. CNAs from 21 long-term care institutions in Taiwan were recruited., Results: This study included 118 female and 26 male CNAs (response rate = 80%). Mean age was 46.8 years. A moderately negative correlation was found between workplace resilience and stress. Overall, being a woman and parent were found to be significantly correlated with CNAs' resilience. Furthermore, resilience and shift work were important predictors of stress., Conclusion: We suggest that leadership and management pay more attention to CNAs' basic demographic background information. Furthermore, timely, relevant strategies can be provided to enhance resilience and reduce workplace stress. [ Journal of Gerontological Nursing, 50 (7), 19-26.].

ALI is a grave medical ailment that manifests as abrupt inflammation of the lungs and diminished oxygen levels. It poses a considerable challenge to the medical fraternity, with elevated rates of morbidity and mortality. Our research endeavors to investigate the potential of hibifolin, a flavonoid glucuronide, imbued with potent antioxidant properties, and its molecular mechanism to combat LPS-induced ALI in mice. The study utilized ICR mice to create an ALI model induced by LPS. Prior to LPS administration, hibifolin was given at 10, 30, or 50 mg/kg, or dexamethasone was given at 1 mg/kg to assess its preventative impact. Changes in lung tissue, pulmonary edema, and lipid peroxidation were analyzed using H&E stain assay, lung wet/dry ratio assay, and MDA formation assay, respectively. Activity assay kits were used to measure MPO activity and antioxidative enzymes (SOD, CAT, GPx) activity in the lungs. Western blot assay was used to determine the phosphorylation of Nrf-2 and AMPK2 in the lungs. Hibifolin demonstrated a concentration-dependent improvement in LPS-induced histopathologic pulmonary changes. This treatment notably mitigated pulmonary edema, lipid peroxidation, and MPO activity in ALI mice. Additionally, hibifolin successfully restored antioxidative enzyme activity in the lungs of ALI mice. Moreover, hibifolin effectively promoted Nrf-2 phosphorylation and reinstated AMPK2 phosphorylation in the lungs of ALI mice. The results indicate that hibifolin could effectively alleviate the pathophysiological impact of LPS-induced ALI. This is likely due to its antioxidative properties, which help to restore antioxidative enzyme activity and activate the AMPK2/Nrf2 pathway. These findings are valuable in terms of enhancing our knowledge of ALI treatment and pave the way for further investigation into hibifolin as a potential therapeutic option for lung injuries., (© 2024 Wiley Periodicals LLC.)

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.)

Metal-organic frameworks (MOFs) are porous materials with potential in biomedical applications such as sensing, drug delivery, and radiosensitization. However, how to tune the properties of the MOFs for such applications remains challenging. Herein, we synthesized two MOFs, Zr-PEB and Hf-PEB. Zr-PEB can be classified as porous interpenetrated zirconium frameworks (PIZOFs) and Hf-PEB is its analogue. We controlled their sizes while maintaining their crystal structure by employing a coordination modulation strategy. They were designed to serve as sensitizer for X-ray therapy and as potential drug carriers. Comprehensive characterizations of the MOFs' properties have been conducted, and the in vitro biological impacts have been studied. Since viability assay showed that Hf-PEB was more biocompatible compared to Zr-PEB, the cellular uptake of Hf-PEB by cells was evaluated using both fluorescence microscopy and soft X-ray tomography (SXT), and the three-dimensional structure of Hf-PEB in cells was observed. The results revealed the potential of Zr-PEB and Hf-PEB as nanomaterials for biomedical applications and demonstrated that SXT is an effective tool to assist the development of such materials.