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Wai-Tao Chan,1–3 Cheng-Che Liu,4 Jen-Shiu Chiang Chiau,5 Shang-Ting Tsai,6 Chih-Kai Liang,6 Mei-Lien Cheng,5 Hung-Chang Lee,7,8 Chun-Yun Yeung,1,3,9 Shao-Yi Hou2,6 1Department of Pediatric Gastroenterology, Hepatology and Nutrition, MacKay Children’s Hospital, 2Graduate Institute of Engineering Technology, National Taipei University of Technology, 3Mackay Medicine, Nursing, and Management College, 4Institute of Preventive Medicine, National Defense Medical Center, Taipei, 5Department of Medical Research, MacKay Memorial Hospital, Hsinchu, 6Graduate Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei, 7Department of Pediatrics, MacKay Memorial Hospital, Hsinchu, 8Department of Pediatrics, Taipei Medical University, Taipei, 9Department of Medicine, Mackay Medical College, New Taipei, Taiwan, Republic of China Abstract: Silica nanoparticles (SiNPs) are being studied and used for medical purposes. As nanotechnology grows rapidly, its biosafety and toxicity have frequently raised concerns. However, diverse results have been reported about the safety of SiNPs; several studies reported that smaller particles might exhibit toxic effects to some cell lines, and larger particles of 100 nm were reported to be genotoxic to the cocultured cells. Here, we investigated the in vivo toxicity of SiNPs of 150 nm in various dosages via intravenous administration in mice. The mice were observed for 14 days before blood examination and histopathological assay. All the mice survived and behaved normally after the administration of nanoparticles. No significant weight change was noted. Blood examinations showed no definite systemic dysfunction of organ systems. Histopathological studies of vital organs confirmed no SiNP-related adverse effects. We concluded that 150 nm SiNPs were biocompatible and safe for in vivo use in mice. Keywords: in vivo, mice, silica nanoparticle, nanotoxicity

Freezing of gait (FOG) is a disabling motor symptom prevalent in patients with Parkinson's disease (PD); however, its pathophysiological mechanisms are poorly understood. This study aimed to investigate whole-brain functional connectivity (FC) pattern alterations in PD patients with FOG. A total of 18 PD patients, 10 with FOG (PD-FOG) and 8 without FOG (PD-nFOG), and 10 healthy controls were enrolled. High-resolution 3D T1-weighted and resting-state functional MRI (rs-fMRI) data were obtained from all participants. The groups' internetwork connectivity differences were explored with rs-fMRI FC using seed-based analysis and graph theory. Multiple linear regression analysis estimated the relationship between FC changes and clinical measurements. Rs-fMRI analysis demonstrated alterations in FC in various brain regions between the three groups. Freezing of Gait Questionnaire severity was correlated with decreased brain functional connection between Vermis12 and the left temporal occipital fusiform cortex (r = -0.82, P < .001). Graph theory topological metrics indicated a decreased clustering coefficient in the right superior temporal gyrus in the PD-nFOG group. PD-FOG patients exhibited a compensatory increase in connectivity between the left inferior frontal gyrus language network and the postcentral gyrus compared to PD-nFOG patients. Further, the decreased connection between Vermis 12 and the left temporal occipital fusiform cortex may serve as a potential neuroimaging biomarker for tracking PD-FOG and distinguishing between PD subtypes., (© 2024 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Abstract: BACKGROUND: Idiopathic intracranial hypertension (IIH) is a neurological disorder characterized by elevated intracranial pressure, affecting predominantly obese women of childbearing age. Early recognition and comprehensive management are vital for preventing severe complications, particularly vision loss. METHODS: This study reports a case of a 27-year-old woman who presented with chronic headaches and blurred vision. Notable findings included headaches that were intensified upon waking and exacerbated by activities that elevated intracranial pressure. The patient also reported nausea, vomiting, transient visual obscurations, and pulsatile tinnitus. After a clinical examination, she was given a diagnosis of IIH. RESULTS: The patient underwent a lumbar-peritoneal shunt procedure to alleviate her symptoms in conjunction with medication treatment. This case study highlights the importance of a multidisciplinary approach in diagnosing and treating IIH. In particular, weight management emerged as a crucial preventive measure against IIH recurrence. CONCLUSION: A multidisciplinary team strategy can enhance outcomes and quality of life, accentuating the need for continued research into IIH recurrence, treatments, and wider implications., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 American Association of Neuroscience Nurses.)

Abstract: BACKGROUND: Stroke is a significant cause of disability. Family Informal caregivers face numerous stressors. This study examines whether social support during hospitalization would mediate the relationship between care time per day and stress in family caregivers of stroke patients. METHODS: A cross-sectional study design in Taiwan recruited 137 family caregivers. Descriptive information forms, the Caregiver Strain Index, and the Social Support Scale were used to collect data. RESULTS: Social support was negatively correlated with stress (r = -0.23, P = .006). By contrast, caregiving hours and physical support were significantly associated with psychological stress. Physical support mediated the association between caregiving hours and psychological stress (95% CI = 0.000-0.005), accounting for 22.02% of the total effect. CONCLUSION: Social support decreased family caregiver stress, notably psychological stress, due to prolonged care of 18 hours per day in the hospital. Physical support resources to alleviate caregiver stress., Competing Interests: Conflicts of interest: The authors declare no conflicts of interest to disclose., (Copyright © 2024 American Association of Neuroscience Nurses.)

Background: Blood-brain barrier (BBB) breakdown is associated with neurodegeneration and cognitive impairment. Cerebral small vessel disease (CSVD) is also common in idiopathic normal pressure hydrocephalus (iNPH). Biomarkers in the cerebrospinal fluid (CSF) may reflect the severity of neuropathological damage and indicate a relationship between BBB integrity and iNPH and its surgical outcome. We investigated the association of CSVD and comorbidity-related CSF biomarkers with shunt outcomes in iNPH., Materials and Methods: This prospective cohort study recruited 53 patients with iNPH, who were subgrouped by CSVD severity. CSF proteins were analyzed, including soluble platelet-derived growth factor receptor-β (sPDGFR-β), Alzheimer's disease biomarkers, neurofilament light chain (NfL), and triggering receptor expressed on myeloid cells 2 (Trem2). We assessed symptom improvement, investigated its association with biomarkes levels, calculated protein cutoffs for surgical outcomes using receiver operating characteristic (ROC) curves, and compared model predictions using different proteins using hierarchical regression analysis., Results: Among patients with iNPH, 74% had comorbid CSVD. Patients with severe CSVD exhibited significantly higher sPDGFR-β levels (P=0.019) and better postoperative performance (β=0.332, t=2.174, P=0.039; r=0.573, P=0.001). Analysis of the predictive potential of the biomarkers showed that sPDGFR-β was predictive of surgical outcomes (area under curve=0.82, sensitivity=66.8%, specificity=94.7%). A Comparison of the models revealed a greater effect of sPDGFR-β (Adjusted R2=0.247, ∆R2=0.160, ∆F(1, 37)=8.238, P=0.007) on cognitive improvement., Conclusion: This study highlighted the relevance of CSF biomarkers in assessing CSVD severity and predicting iNPH surgical outcome. CSF shunt surgery may provide an alternative treatment for neurodegenerative diseases with BBB breakdown and dysfunctional CSF clearance., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Interobserver variations in the pathology of common astrocytic tumors impact diagnosis and subsequent treatment decisions. This study leveraged a residual neural network-50 (ResNet-50) in digital pathological images of diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma to recognize characteristic pathological features and perform classification at the patch and case levels with identification of incorrect predictions. In addition, cellularity and nuclear morphological features, including axis ratio, circularity, entropy, area, irregularity, and perimeter, were quantified via a hybrid task cascade (HTC) framework and compared between different characteristic pathological features with importance weighting. A total of 95 cases, including 15 cases of diffuse astrocytoma, 11 cases of anaplastic astrocytoma, and 69 cases of glioblastoma, were collected in Taiwan Hualien Tzu Chi Hospital from January 2000 to December 2021. The results revealed that an optimized ResNet-50 model could recognize characteristic pathological features at the patch level and assist in diagnosis at the case level with accuracies of 0.916 and 0.846, respectively. Incorrect predictions were mainly due to indistinguishable morphologic overlap between anaplastic astrocytoma and glioblastoma tumor cell area, zones of scant vascular lumen with compact endothelial cells in the glioblastoma microvascular proliferation area mimicking the glioblastoma tumor cell area, and certain regions in diffuse astrocytoma with too low cellularity being misrecognized as the glioblastoma necrosis area. Significant differences were observed in cellularity and each nuclear morphological feature among different characteristic pathological features. Furthermore, using the extreme gradient boosting (XGBoost) algorithm, we found that entropy was the most important feature for classification, followed by cellularity, area, circularity, axis ratio, perimeter, and irregularity. Identifying incorrect predictions provided valuable feedback to machine learning design to further enhance accuracy and reduce errors in classification. Moreover, quantifying cellularity and nuclear morphological features with importance weighting provided the basis for developing an innovative scoring system to achieve objective classification and precision diagnosis among common astrocytic tumors.

Intracerebral hemorrhage (ICH) is a life-threatening condition associated with significant morbidity and mortality. This study investigates transcriptomic alterations in rodent models of ICH and severe ICH to shed light on the genetic pathways involved in hemorrhagic brain injury. We performed principal component analysis, revealing distinct principal component segments of normal rats compared to ICH and severe ICH rats. We employed heatmaps and volcano plots to identify differentially expressed genes and utilized bar plots and KEGG pathway analysis to elucidate the molecular pathways involved. We identified a multitude of differentially expressed genes in both the ICH and severe ICH models. Our results revealed 5679 common genes among the normal, ICH, and severe ICH groups in the upregulated genes group, and 1196 common genes in the downregulated genes, respectively. A volcano plot comparing these groups further highlighted common genes, including PDPN, TIMP1, SERPINE1, TUBB6, and CD44. These findings underscore the complex interplay of genes involved in inflammation, oxidative stress, and neuronal damage. Furthermore, pathway enrichment analysis uncovered key signaling pathways, including the TNF signaling pathway, protein processing in the endoplasmic reticulum, MAPK signaling pathway, and Fc gamma R-mediated phagocytosis, implicated in the pathogenesis of ICH.

Well-being can reflect people's psychological conditions and be used alongside physiological parameters to evaluate patients' physical and mental health. The modern medical environment increasingly incorporates digital carriers, human-computer interaction devices, sensible spaces, and the execution of suitable algorithms. Slow design in healthy human-computer interaction is often used to reflect people's dependence on or support from behaviors or objects, promoting the stability of behaviors as well as meaningful and positive changes. Therefore, in this study, we propose a slow sensing model, develop a Slow Well-Being Gardening system, and use it to evaluate behavioral data from radiation therapy patients during treatment sessions and horticultural therapy. This study is based on SENS and slow design, setting the hospital lounge as a sensible space and establishing a sensor system. After a 10-day inspection, the process was evaluated and verified. Ultimately, data from facial detection (smile) and HRV showed that the patients in the experimental group experienced a significant improvement in their well-being, feeling better than those in the control group who maintained the most common state in normal treatment. Therefore, it can be inferred that the Slow Well-Being Gardening model is indeed valid and can be further developed.

Detecting and analyzing the local environment is crucial for investigating the dynamical processes of crystal nucleation and shape colloidal particle self-assembly. Recent developments in machine learning provide a promising avenue for better order parameters in complex systems that are challenging to study using traditional approaches. However, the application of machine learning to self-assembly on systems of particle shapes is still underexplored. To address this gap, we propose a simple, physics-agnostic, yet powerful approach that involves training a multilayer perceptron (MLP) as a local environment classifier for systems of particle shapes, using input features such as particle distances and orientations. Our MLP classifier is trained in a supervised manner with a shape symmetry-encoded data augmentation technique without the need for any conventional roto-translations invariant symmetry functions. We evaluate the performance of our classifiers on four different scenarios involving self-assembly of cubic structures, two-dimensional and three-dimensional patchy particle shape systems, hexagonal bipyramids with varying aspect ratios, and truncated shapes with different degrees of truncation. The proposed training process and data augmentation technique are both straightforward and flexible, enabling easy application of the classifier to other processes involving particle orientations. Our work thus presents a valuable tool for investigating self-assembly processes on systems of particle shapes, with potential applications in structure identification of any particle-based or molecular system where orientations can be defined., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Cerebrovascular accidents, also known as strokes, represent a major global public health challenge and contribute to substantial mortality, disability, and socioeconomic burden. Multidisciplinary approaches for poststroke therapies are crucial for recovering lost functions and adapting to new limitations. This review discusses the potential of neuromodulation techniques, repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, spinal cord stimulation (SCS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS), as innovative strategies for facilitating poststroke recovery. Neuromodulation is an emerging adjunct to conventional therapies that target neural plasticity to restore lost function and compensate for damaged brain areas. The techniques discussed in this review have different efficacies in enhancing neural plasticity, optimizing motor recovery, and mitigating poststroke impairments. Specifically, rTMS has shown significant promise in enhancing motor function, whereas SCS has shown potential in improving limb movement and reducing disability. Similarly, VNS, typically used to treat epilepsy, has shown promise in enhancing poststroke motor recovery, while DBS may be used to improve poststroke motor recovery and symptom mitigation. Further studies with standardized protocols are warranted to elucidate the efficacy of these methods and integrate them into mainstream clinical practice to optimize poststroke care., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Tzu Chi Medical Journal.)

Background: Patients with idiopathic normal-pressure hydrocephalus (iNPH) are predisposed to developing dementing disorders. Cerebrospinal fluid (CSF) shunt implantation is a treatment used to improve the motor and cognitive disabilities of these patients; however, its effect on the risk of developing dementing disorders remains unclear. We conducted a population-based propensity-weighted cohort study to investigate whether CSF shunt surgery may reduce the risk of subsequently developing dementia, Alzheimer's disease (AD), and vascular dementia in iNPH patients., Methods: Patients aged ≥ 60 years who were diagnosed with iNPH (n = 2053) between January 2001 and June 2018 were identified from the Taiwan National Health Insurance Research Database. Various demographic characteristics (age, sex, and monthly income) and clinical data (incidence year, comorbidities, and Charlson comorbidity index) were collected and divided into the shunt surgery group (SSG) and the non-shunt surgery group (NSSG). Stabilized inverse probability of treatment weighting by using the propensity score was performed to achieve a balanced distribution of confounders across the two study groups. The cumulative incidence rate and risk of dementing disorders were estimated during a 16-year follow-up period., Results: After weighting, the data of 375.0 patients in SSG and 1677.4 patients in NSSG were analyzed. Kaplan-Meier curve analysis indicated that the cumulative incidence rate of AD (p = 0.009), but not dementia (p = 0.241) and vascular dementia (p = 0.761), in SSG was significantly lower than that in NSSG over the 16-year follow-up period. Cox proportional hazards regression analysis revealed that SSG had a reduced hazard ratio (HR) for developing AD [HR (95% CI) 0.17 (0.04-0.69)], but not for dementia [HR (95% CI) 0.83 (0.61-1.12)] and vascular dementia [HR (95% CI) 1.18 (0.44-3.16)], compared with NSSG. Further Fine-Gray hazard regression analysis with death as a competing event demonstrated that SSG had a reduced subdistribution HR (sHR) for developing dementia [sHR (95% CI) 0.74 (0.55-0.99)] and AD [sHR (95% CI) 0.15 (0.04-0.61)], but not for vascular dementia [sHR (95% CI) 1.07 (0.40-2.86)]., Conclusion: CSF shunt surgery is associated with reduced risks of the subsequent development of dementia and AD in iNPH patients. Our findings may provide valuable information for assessing the benefit-to-risk profile of CSF shunt surgery., (© 2024. The Author(s).)

The purpose of this study was to investigate the differences in attack time and lower limb biomechanics when performing fencing lunge with fencing shoes (FS) and commonly used court shoes (CS). Additionally, the study aimed to evaluate whether fencing shoes with a heel cup (FSH) could reduce lower limb impact. Thirteen female collegiate fencers who had participated in national-level competitions were recruited for this study. Participants performed the lunge on a human-shaped target while wearing FS, FSH, or CS in a randomized order. Biomechanical data were collected using a 3D motion analysis system synchronized with a force plate. A signal light, and an accelerometer were attached to the target's head to initiate lunge movement and detect hit moment for calculating attack time. Attack time was significantly shorter when wearing FS (0.92 ± 0.05 s) and FSH (0.93 ± 0.07 s) compared to CS (0.96 ± 0.06 s). The maximum angular velocity of ankle plantarflexion in rear foot push-off phase was significantly slower when wearing FS and FSH than when wearing CS. The maximum knee posterior shear force, maximum knee flexion moment, and maximum ankle medial shear force during the front foot step phase were significantly greater when wearing FS than when wearing CS. These forces were significantly reduced or nearly significantly reduced when wearing FSH, and there were no significant differences compared to wearing CS. The maximum ankle medial shear force during the push-off phase in rear foot was the greatest when wearing FS but decreased significantly when using FSH. However, this force was still greater than when wearing CS. Wearing FS resulted in a higher loading rate (LR) on the front foot. This LR was reduced when a heel cup was used but still remained higher than when wearing CS. There were no significant differences in the forward extension of body, maximum ground reaction force, or center of pressure displacement during front foot step and rear foot push-off phases among the three shoe conditions. Wearing FS can enhance lunge performance, and the use of a heel cup can effectively reduce lower limb impact., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Chang, Chao, Nicholls and Tsai.)

Fibromyalgia (FM) is a complex, chronic, widespread pain syndrome that can cause significant health and economic burden. Emerging evidence has shown that neuroinflammation is an underlying pathological mechanism in FM. Toll-like receptors (TLRs) are key mediators of the immune system. TLR4 is expressed primarily in microglia and regulates downstream signaling pathways, such as MyD88/NF-κB and TRIF/IRF3. It remains unknown whether electroacupuncture (EA) has therapeutic benefit in attenuating FM pain and what role the TLR4 pathway may play in this effect. We compared EA with sham EA to eliminate the placebo effect due to acupuncture. We demonstrated that intermittent cold stress significantly induced an increase in mechanical and thermal FM pain in mice (mechanical: 2.48 ± 0.53 g; thermal: 5.64 ± 0.32 s). EA but not sham EA has an analgesic effect on FM mice. TLR4 and inflammatory mediator-related molecules were increased in the thalamus, medial prefrontal cortex, somatosensory cortex (SSC), and amygdala of FM mice, indicating neuroinflammation and microglial activation. These molecules were reduced by EA but not sham EA. Furthermore, a new chemogenetics method was used to precisely inhibit SSC activity that displayed an anti-nociceptive effect through the TLR4 pathway. Our results imply that the analgesic effect of EA is associated with TLR4 downregulation. We provide novel evidence that EA modulates the TLR4 signaling pathway, revealing potential therapeutic targets for FM pain.

Background: Incivility and bullying in the nursing workplace may induce psychological trauma and increase staff turnover, however, the effects can be mitigated by cognitive rehearsal therapy. Smartphone education applications have emerged as an important educational tool in recent years. However, to date, no educational applications have been developed that combine cognitive rehearsal approaches with clinical situations. Therefore, in this study an education application (Easy Play Communication) was developed and tested to address incivility and bullying in the nursing workplace., Design/methods: This study design was employed in two phases. Phase 1 (February 2020-March 2021) combined analysis, design, development, implementation, and evaluation (ADDIE model) stages in the application development process. This phase involved conducting research into educational training and cognitive rehearsal literature, consultations with seven experts in related fields and administering a user needs questionnaire among 41 nurses. Phase 2 (April 2021-December 2021) was a pilot test phase, where 47 Mandarin and Taiwanese speaking nurses used the application to conduct cognitive rehearsal training. Changes in workplace incivility and bullying were tested using a pretest-posttest design. The posttest was conducted one week after the pretest., Results: Phase 1 showed user satisfaction with the app's accessibility (96.3 %), practicality (81.4 %), willingness to use (92.6 %), information content (88.9 %), information quality (88.9 %), and interface quality (88.9 %). Phase 2 showed that participants' perceived incivility in their interactions with other nurses, physicians, and patients and their family members decreased over the study period., Discussion/implications: The findings indicate that smartphone applications combining theoretical knowledge with practical exercises can have a positive impact on nurses in the context of workplace incivility and bullying. We also demonstrated a development process that can be used to build applications for clinical nurses., Competing Interests: Declaration of competing interest The named authors have no conflict of interest, financial or otherwise., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In this study, a fractal absorber was designed to enhance light absorptivity and improve the efficiency of converting solar energy into electricity for a range of solar energy technologies. The absorber consisted of multiple layers arranged from bottom to top, and the bottom layer was made of Ti metal, followed by a thin layer of MgF 2 atop it. Above the two layers, a structure comprising square pillars formed by three layers of Ti/MgF 2 /Ti was formed. This pillar was encompassed by a square hollow with cylindrical structures made of Ti material on the exterior. The software utilized for this study was COMSOL Multiphysics ® (version 6.0). This study contains an absorption spectrum analysis of the various components of the designed absorber system, confirming the notion that achieving ultra-wideband and perfect absorption resulted from the combination of the various components. A comprehensive analysis was also conducted on the width of the central square pillar, and the analysis results demonstrate the presence of several remarkable optical phenomena within the investigated structure, including propagating surface plasmon resonance, localized surface plasmon resonance, Fabry-Perot cavity resonance, and symmetric coupling plasma modes. The optimal model determined through this software demonstrated that broadband absorption in the range of 276 to 2668 nm, which was in the range of UV-B to near-infrared, exceeded 90.0%. The average absorption rate in the range of 276~2668 nm reached 0.965, with the highest achieving a perfect absorptivity of 99.9%. A comparison between absorption with and without outer cylindrical structures revealed that the resonance effects significantly enhanced absorption efficiency, as evidenced by a comparison of electric field distributions.

Purpose: The global fight against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has led to widespread vaccination efforts, yet the optimal dosing schedule for SARS-CoV-2 vaccines remains a subject of ongoing research. This study aims to investigate the effectiveness of administering two booster doses as the third and fourth doses at different intervals to enhance vaccine protection., Materials and Methods: This study was conducted at a military regional hospital operated by the Ministry of National Defense in Taiwan. A cohort of vaccinated individuals was selected, and their vaccine potency was assessed at various time intervals following their initial vaccine administration. The study participants received booster doses as the third and fourth doses, with differing time intervals between them. The study monitored neutralizing antibody titers and other relevant parameters to assess vaccine efficacy., Results: Our findings revealed that the potency of the SARS-CoV-2 vaccine exhibited a significant decline 80 days after the initial vaccine administration. However, a longer interval of 175 days between booster injections resulted in significantly higher neutralizing antibody titers. The individuals who received the extended interval boosters exhibited a more robust immune response, suggesting that a vaccine schedule with a 175-day interval between injections may provide superior protection against SARS-CoV-2., Conclusion: This study underscores the importance of optimizing vaccine booster dosing schedules to maximize protection against SARS-CoV-2. The results indicate that a longer interval of 175 days between the third and fourth doses of the vaccine can significantly enhance the neutralizing antibody response, potentially offering improved protection against the virus. These findings have important implications for vaccine distribution and administration strategies in the ongoing battle against the SARS-CoV-2 pandemic. Further research and large-scale trials are needed to confirm and extend these findings for broader public health implications., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Korean Vaccine Society.)

Whole-cell biosensors have demonstrated promising capabilities in detecting target molecules. However, their limited selectivity and precision can be attributed to the broad substrate tolerance of natural proteins. In this study, we aim to enhance the performance of whole-cell biosensors by incorporating of logic AND gates. Specifically, we utilize the HrpR/S system, a widely employed hetero-regulation module from Pseudomonas syringae in synthetic biology, to construct an orthogonal AND gate in Escherichia coli. To accomplish this, we compare the HrpR/S system with self-associating split fluorescent proteins using the Spy Tag/Spy Catcher system. Our objective is to selectively activate a reporter gene in the presence of both IPTG and Hg(II) ions. Through systematic genetic engineering and evaluation of various biological parts under diverse working conditions, our research demonstrates the utility of self-associating split fluorescent proteins in developing high-performance whole-cell biosensors. This approach offers advantages such as engineering simplicity, reduced basal activity, and improved selectivity. Furthermore, the comparison with the HrpR/S system serves as a valuable control model, providing insights into the relative advantages and limitations of each approach. These findings present a systematic and adaptable strategy to overcome the substrate tolerance challenge faced by whole-cell biosensors., 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 © 2023 Elsevier B.V. All rights reserved.)

Determining carbohydrate structures, such as their compositions, linkage positions, and in particular the anomers and stereoisomers, is a great challenge. Isomers of different anomers or stereoisomers have the same sequences of chemical bonds, but have different orientations of some chemical bonds which are difficult to be distinguished by mass spectrometry. Collision-induced dissociation (CID) tandem mass spectroscopy (MS/MS) is a widely used technique for characterizing carbohydrate structures. Understanding the carbohydrate dissociation mechanism is important for obtaining the structural information from MS/MS. In this work, we studied the CID mechanism of galactose- N -acetylgalactosamine (Gal-GalNAc) and glucose- N -acetylglucosamine (Glc-GlcNAc) disaccharides with 1→3 and 1→4 linkages. For Gal-GalNAc disaccharides, the CID mass spectra of sodium ion adducts show significant difference between the α- and β-anomers of GalNAc at the reducing end, while no difference in the CID mass spectra between two anomers of Glc-GlcNAc disaccharides was found. Quantum chemistry calculations show that for Gal-GalNAc disaccharides, the difference of the dissociation barriers between dehydration and glycosidic bond cleavage is significantly small in the β-anomer compared to that in the α-anomer; while these differences are similar between the α- and β-anomers of Glc-GlcNAc disaccharides. These differences can be attributed to the different orientations of hydroxyl and N -acetyl groups located at GalNAc and GlcNAc. The calculation results are consistent with the CID spectra of isotope labelled disaccharides. Our study provides an insight into the CID of 1→3 and 1→4 linked Gal-GalNAc and Glc-GlcNAc disaccharides. This information is useful for determining the anomeric configurations of GalNAc in oligosaccharides.

(1) Background: Salivary gland tumors are rare in the head and neck. To determine the need and extent of surgical intervention, fine needle aspiration (FNA) is a widely accepted tool to approach salivary gland lesions. However, the FNA cytology varies between entities, while the lack of uniform terminology makes diagnosis more challenging. Since establishing the Milan system for reporting salivary gland cytopathology (MSRSGC) has become an increasingly accepted reporting standard, further examination and detailed recommendations were needed. (2) Methods: Between April 2013 and October 2021, 375 cases with FNA and salivary gland resection were retrospectively collected. All FNA specimens were reclassified according to the criteria of MSRSGC. After surgical excision, the FNA data were compared with the histological diagnosis to estimate the risk of malignancy (ROM), the risk of neoplasm (RON), and the diagnostic accuracy for each diagnostic category. (3) Results: Our cohort's distribution of ROM and RON was similar to the MSRSGC's recommendation. Carcinoma ex pleomorphic adenoma (CXPA) has the highest rate (66.7%) of misdiagnosed as a nonneoplastic lesion or benign salivary gland tumor. Pleomorphic adenoma (PA) and Warthin's tumor were the most common benign salivary gland tumors, while the cytology diagnosis of Warthin's tumor seems more challenging than PAs. (4) Conclusions: Despite the convenience and effectiveness of MSRSGC, we suggest close follow-up, re-biopsy, or surgical removal for salivary lesions even in Milan IVA-Benign for possibly missing FNA of malignancy, mixed lesions, or prevention of malignant transformation.

Differentiation of stereoisomers that are only dissimilar in the orientation of chemical bonds in space by mass spectrometry remains challenging. Structural determination of carbohydrates by mass spectrometry is difficult, mainly due to the large number of stereoisomers in carbohydrates. Arabinose and xylose are pentose stereoisomers typically present in plant polysaccharides and exist in α- and β-anomeric configurations of furanose and pyranose forms. Conventional methods used to determine the structures of polysaccharides include hydrolysis of polysaccharides into oligosaccharides followed by identification of these oligosaccharides' structures individually through nuclear magnetic resonance spectroscopy (NMR). Although the sensitivity of mass spectrometry is much higher than that of NMR, conventional mass spectrometry provides only limited useful information on oligosaccharide structure determination, only the linkage positions of glycosidic bonds. In this study, we demonstrated a mass spectrometry method for the identification of linkage positions, anomeric configurations, and monosaccharide stereoisomers of intact oligosaccharides consisting of arabinose and xylose. We separated arabinose and xylose monosaccharides into α-furanose, β-furanose, α-pyranose, and β-pyranose forms through high-performance liquid chromatography and obtained the corresponding collision-induced dissociation mass spectra. Using these monosaccharide spectra and a flow chart consisting of the proper CID sequences derived from the dissociation mechanisms of pentose, a simple multi-stage tandem mass spectrometry method for structural identification of intact oligosaccharides consisting of arabinose and xylose was developed. The new mass spectrometry method provides a simple method for determining the structure of polysaccharides consisting of arabinose and xylose. The flow chart can be used in computer coding for automation, an ultimate goal for oligosaccharide structure determination.

The efficacy of current pharmaceutical treatments for fibromyalgia are limited. Vitamin D has shown promise in relieving pain. However, there is a lack of comprehensive analysis of psychological outcomes with vitamin D supplementation in fibromyalgia. This study aimed to investigate the impact of vitamin D supplementation on psychological outcomes and quality of life in fibromyalgia patients, given the unmet clinical need for effective treatment options. A meta-analysis of randomized controlled trials comparing vitamin D to placebo and prospective studies examining changes before and after vitamin D supplementation for patients with fibromyalgia was conducted to evaluate the effects of vitamin D on psychological outcomes, quality of life, and pain scores in patients with fibromyalgia. Databases were searched for relevant articles published from earliest available date to October 31, 2022. (PROSPERO number, CRD42022369889). We included 8 trials with a total of 694 participants and found that vitamin D supplementation had significant positive effects on physical function (standard mean differences (SMD) = 0.44, 95% CI = [0.10, 0.77 ]), role limitations due to emotional health (SMD = 0.57, 95% CI = [0.32, 0.82]), social function (SMD = 0.50, 95% CI = [0.08, 0.93]), and general health (SMD = 0.36, 95% CI = [0.11, 0.61]). Improvement of the Fibromyalgia Impact Questionnaire (FIQ) scores was noted (SMD = -0.414, 95% CI = [-0.808, -0.021]), but not on the Visual Analog Scale (VAS) (SMD = -0.15, 95% CI = [-0.771, 0.471]) and the Beck's Depression Inventory (BDI) scores (SMD = -0.456, 95% CI = [-1.27, 0.30]). In conclusion, vitamin D supplementation might be an alternative option for improvement of psychological outcomes and quality of life in patients with fibromyalgia.

Dysphagia affects 60-75% of patients treated for head and neck cancer (HNC). We aimed to evaluate the association between residue severity and airway invasion severity using a videofluoroscopic swallowing study and identify risk factors for poor penetration-aspiration outcomes in patients with dysphagia treated for HNC. Penetration-Aspiration Scale (PAS) was used to assess airway invasion severity, while residue severity was assessed using both the Bolus Residue Scale (BRS) for residue location and the Normalized Residue Ratio Scale (NRRS) for residue amount. Relevant covariates were adjusted in the logistic regression models to account for potential confounding. Significantly higher abnormal PAS was reported for increased piriform sinus NRRS (NRRSp) [odds ratio (OR), 4.81; p = 0.042] with liquid swallowing and increased BRS value (OR, 1.52; p = 0.014) for semi-liquid swallowing in multivariate analysis. Tumor location, older age, and poorer Functional Oral Intake Scale (FOIS) were significant factors for abnormal PAS in both texture swallowings. After adjusting for confounding factors (sex, age, and FOIS score), NRRS model in liquid swallowing (area under the curve [AUC], 0.83; standard error = 0.04, 95% confidence interval [CI]: 0.75, 0.91) and BRS in semi-liquid swallowing (AUC, 0.83; SE = 0.04; 95% CI: 0.76, 0.91) predicted abnormal PAS. The results indicate that while assessing residue and swallowing aspiration in patients with HNC, it is important to consider age, tumor location, and functional swallowing status. The good predictability of abnormal PAS with BRS and NRRS indicated that residue location and amount were both related to the aspiration event in patients with HNC., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting both motor functions and quality of life (QoL). This study compared motor symptoms and QoL in patients with PD before and at 1 and 5 years after subthalamic nucleus deep brain stimulation (STN-DBS) surgery in Taiwan. This study included 53 patients with PD undergoing STN-DBS. The motor symptoms improved by 39.71 ± 26.52% and 18.83 ± 37.15% in the Unified Parkinson's Disease Rating Scale (UPDRS) part II and by 36.83 ± 22.51% and 22.75 ± 36.32% in the UPDRS part III at 1 and 5 years after STN-DBS in the off-medication/on-stimulation state, respectively. The Hoehn and Yahr stage significantly improved at the 1-year follow-up but declined progressively and returned to the baseline stage 5 years post-surgery. The Schwab and England Activities of Daily Living improved and sustained for 5 years following STN-DBS. Levodopa equivalent daily dose decreased by 35.32 ± 35.87% and 15.26 ± 65.76% at 1 and 5 years post-surgery, respectively. The QoL revealed significant improvement at 1 year post-surgery; however, patients regressed to near baseline levels 5 years post-surgery. The long-term effects of STN-DBS on motor symptoms were maintained over 5 years after STN-DBS surgery. At the same time, STN-DBS had no long-lasting effect on QoL. The study findings will enable clinicians to become more aware of visible and invisible manifestations of PD.

From a porous structure perspective, the one-stage de novo synthesis method and impregnation method were applied to synthesize Ag(I) ion-containing ZIF-8 samples. With the de novo synthesis method, Ag(I) ions could be located inside micropores or adsorbed on the external surface of the ZIF-8 by selecting AgNO 3 in water or Ag 2 CO 3 in ammonia solution as precursors, respectively. The ZIF-8 confining Ag(I) ion exhibited a much lower constant releasing rate than the Ag(I) ion adsorbed on the ZIF-8 surface in artificial seawater. As such, strong diffusion resistance in association with the confinement effect is contributed by ZIF-8's micropore. On the other hand, the release of Ag(I) ions adsorbed on the external surface was diffusion limited. Therefore, the releasing rate would reach a maximum not increasing with Ag(I) loading in the ZIF-8 sample.

Introduction: The current standard surgical treatment for cerebrospinal fluid diversion is a ventriculoperitoneal shunt (VPS) implantation. Lumboperitoneal shunts (LPS) are an alternative treatment for communicating hydrocephalus. Prior studies comparing these two included a limited number of participants., Methods: We performed a meta-analysis determined the treatment failure, complications and effectiveness of lumboperitoneal shunt for communicating hydrocephalus. We reviewed studies with clinical and imaging diagnoses of communicating hydrocephalus, all causes and subtypes of communicating hydrocephalus, and studies that analyzed the primary and secondary outcomes listed below. We included randomized controlled trials (RCTs), non-RCTs and retrospective studies. We performed the meta-analysis in R, using a random-effects model and reporting 95% confidence intervals., Results: Data from 25 studies, including 3654 patients, were analyzed. The total complication rates were 12.98% (188/1448) for lumboperitoneal shunt and 23.80% (398/1672) for ventriculoperitoneal shunt. The odds ratio for lumboperitoneal shunt versus ventriculoperitoneal shunt complication rates was 0.29 (95% CI 0.19 to 0.45, p < 0.0001), and the I 2 was 72%. The shunt obstruction/malfunction rate was 3.99% (48/1204) for lumboperitoneal shunt and 8.31% (115/1384) for ventriculoperitoneal shunt (Odds ratio 0.54, 95% CI 0.37 to 0.79, p = 0.002, I 2  = 0%). Based on the Modified Rankin Scale score, there were no differences in effectiveness between lumboperitoneal shunt and ventriculoperitoneal shunt. Nevertheless, lumboperitoneal shunt improved radiological outcomes., Conclusions: This analysis demonstrated that lumboperitoneal shunt is a safe and equally effective choice for treating communicating hydrocephalus. More studies are needed to confirm the safety of lumboperitoneal shunt., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Crystal nucleation is relevant across the domains of fundamental and applied sciences. However, in many cases, its mechanism remains unclear due to a lack of temporal or spatial resolution. To gain insights into the molecular details of nucleation, some form of molecular dynamics simulations is typically performed; these simulations, in turn, are limited by their ability to run long enough to sample the nucleation event thoroughly. To overcome the timescale limits in typical molecular dynamics simulations in a manner free of prior human bias, here, we employ the machine learning-augmented molecular dynamics framework "reweighted autoencoded variational Bayes for enhanced sampling (RAVE)." We study two molecular systems-urea and glycine-in explicit all-atom water, due to their enrichment in polymorphic structures and common utility in commercial applications. From our simulations, we observe multiple back-and-forth nucleation events of different polymorphs from homogeneous solution; from these trajectories, we calculate the relative ranking of finite-sized polymorph crystals embedded in solution, in terms of the free-energy difference between the finite-sized crystal polymorph and the original solution state. We further observe that the obtained reaction coordinates and transitions are highly nonclassical.

Traditional Chinese medicine (TCM) has the characteristics of multi-component, multi-target, and biological systems coordination, which meet the criteria of the network pharmacological application. Therefore, using network pharmacology to discover the relationship between TCM, diseases, and cellular responses is easily achievable. Aging-induced imbalanced homeostasis is a risk factor for Alzheimer's disease (AD), a neuronal disease regulated by multiple genes. Meta-analysis of TCM in metabolic regulation to improve symptoms of AD helps understand the pharmacological effects. The drug targets of TCM can be investigated using a holistic network pharmacology approach to find potential modulators involved in AD-related metabolic pathways. Based on the theoretical prediction of TCM for AD, experimental validation is needed to develop pure compounds for specific treatments., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Tzu Chi Medical Journal.)

Background: To cure advanced hypopharyngeal squamous cell carcinoma (HPSCC), primary operation followed by adjuvant (chemo-)radiotherapy (OP-CRT) or definitive chemoradiation (CCRT) are the two primary options. This study aimed to compare the failure patterns and long-term survival outcomes of HPSCC patients treated with these two strategies. PATIENTS AND METHODS: From 2007 to 2015, 198 pathologically confirmed HPSCC patients receiving either OP-CRT or CCRT were retrospectively reviewed. Failure patterns and survival outcomes stratified by the 7th American Joint Committee on Cancer staging system and treatment modalities were compared., Results: One hundred and eighty-nine patients (95.4%) were stage III/IV and 62 patients (31.3%) received OP-CRT. Median follow-up duration was 4.9 years. Compared with CCRT, OP-CRT provided better 3-year local relapse-free survival for T3 (93 vs 48%, p < 0.0001), T4a (88 vs 37%, p = 0.0005) and better 3-year regional relapse-free survival for N2b+2c (93 vs 60%, p < 0.0001). Of note, for stage IVA subjects, OP-CRT provided better 3-year loco-regional relapse-free survival (85 vs 37%, p < 0.0001), marginal poor 3-year distant metastasis-free survival (62 vs 79%, p = 0.06), but comparable 3-year OS (52 vs 44%, p = 0.37) and 5-year OS (44 vs 31%, p = 0.15) compared with CCRT., Conclusions: For patients with advanced HPSCC, although OP-CRT and CCRT provided similar overall survival, failure patterns were distinct. OP-CRT provided better loco-regional control but was more likely to encounter distant metastases than CCRT. The detailed analysis of failure patterns will pave the way to improve this devastating disease., (© 2022. The Author(s).)

In this chapter, we conducted a systemic literature review for the anti-inflammatory effects of Traditional Chinese Medicine (TCM) applying molecular mechanisms focusing on the neuroinflammation and gut-brain axis in three neuropsychiatric disorders: major depressive disorder, Alzheimer's disease, and Parkinson's disease. We demonstrated the anti-inflammation or immunomodulation effects of TCM, including acupuncture, from basic and clinical research, including cellular and molecular approaches. In conclusion, inflammation plays a critical role in the neuropsychopathological process. At the same time, anti-inflammation seems to be the common biological pathway for the effects of TCM and acupuncture in depression, Alzheimer's disease, and Parkinson's disease., (© 2023. The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.)

Objectives: For patients with glottic insufficiency disease, injection laryngoplasty is a rapid and efficient management option that complements voice therapy. Some studies have indicated that respiratory muscle training may also show promise in patients with voice disorders. However, the effect of respiratory muscle training in patients with glottic insufficiency was reported to be limited, and whether it provides additional benefit after standard management requires further evaluation. We aimed to investigate the effectiveness of inspiratory muscle training on glottis closure and patient-reported voice quality in glottic insufficiency patients who had been treated with hyaluronic acid injection., Study Design: Retrospective observational study., Methods: We included 46 patients with glottic insufficiency who had undergone hyaluronic acid injection. Twenty of them had undergone inspiratory muscle training during three months. We measured patients' changes in glottic status according to the normalized glottal gap area and bowing index, as well as voice quality of life according to the voice handicap index 10 and the voice outcome survey, before and after training., Results: Patients who underwent inspiratory muscle training had higher odds of experiencing better improvement in all scores. The range of odds ratios ranged from 2.5 to 6.3 for changes in scores, and from 3.8 to 22.2 for changes in score percentages. Of note, the effect of training on percentage changes in the normalized glottal gap area score was significant (P= 0.0127) after adjustment for the duration of vocal disease, body mass index and BMI, and history of gastroesophageal reflux disease., Conclusions: Inspiratory muscle training can improve the glottal gap after injection laryngoplasty, and may be applied in clinical practice., Competing Interests: Conflict of interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2022 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

N-linked glycosylation is one of the most important post translational modification of proteins. Various analytical techniques are used for the structural identification of the N-glycans released from proteins through various enzymatic and chemical methods. Although very few side-reaction products are generated during the enzymatic release of N-glycans, this method is expensive and suitable only for small quantities of samples. By contrast, chemical methods can be used for large quantities of samples; however, various side-reaction products are generated when chemical methods are used. Recently, the ammonia-catalyzed release of N-glycans from proteins has been reported to be associated with no typical side reactions. In the present study, we discovered a new side reaction: the epimerization of N-acetylglucosamine present at the reducing end of N-glycans to N-acetylmannosamine. The product of this side reaction interfered with the structural identification N-glycans. We propose a simple method that can help identify this artifact N-glycan isomer and eliminate the aforementioned interference. This simple method widens the applicability of ammonia-catalyzed reactions for N-glycan release from proteins, and is also suitable for N-glycans released using any other alkaline solutions., Competing Interests: Declarationof 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 © 2022 Elsevier Ltd. All rights reserved.)

Recurrent neural networks have seen widespread use in modeling dynamical systems in varied domains such as weather prediction, text prediction and several others. Often one wishes to supplement the experimentally observed dynamics with prior knowledge or intuition about the system. While the recurrent nature of these networks allows them to model arbitrarily long memories in the time series used in training, it makes it harder to impose prior knowledge or intuition through generic constraints. In this work, we present a path sampling approach based on principle of Maximum Caliber that allows us to include generic thermodynamic or kinetic constraints into recurrent neural networks. We show the method here for a widely used type of recurrent neural network known as long short-term memory network in the context of supplementing time series collected from different application domains. These include classical Molecular Dynamics of a protein and Monte Carlo simulations of an open quantum system continuously losing photons to the environment and displaying Rabi oscillations. Our method can be easily generalized to other generative artificial intelligence models and to generic time series in different areas of physical and social sciences, where one wishes to supplement limited data with intuition or theory based corrections., (© 2022. The Author(s).)

Spinal cord injury (SCI) is a severe central nervous system injury that can cause sensory or motor dysfunction. Although mortality rates for people with spinal cord injuries have dropped dramatically with advances in medicine, chronic long-term sequelae after SCI persist. The most bothersome problems reported by patients include pain, spasticity, urinary dysfunction, and loss of motor function. Thus, quality of life (QoL) is an essential issue in chronic SCI. Spinal cord stimulation (SCS) applies an adjustable, nondamaging electrical pulse that can reduce uncomfortable comorbidities and improve mobility, thus enhancing the QoL of patients with SCI. This review summarizes pivotal breakthroughs from SCS for individual clinical impairment from SCI. We conclude that careful evaluation of SCS can help improve neuropathic pain, spasms, motor symptoms, and voiding dysfunction in patients with SCI, thus improving QoL., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Tzu Chi Medical Journal.)

Background/purpose: Effective evaluation of students' self-assessment ability is crucial. This study was to develop a standardized 3D printed teaching model accompanied by structured scoring rubrics for preclinical endodontic training, to appraise students' self-assessment ability, and to evaluate their perceptions of the training system., Methods: The 3D printing model was designed to house a standardized central incisor. Forty-four undergraduate dental students were enrolled and their endodontic performance was self-assessed and also rated by a teaching assistant and a tutor using 3 structured rubrics including access cavity, mechanical preparation, and obturation assessments. In total, 21 rubric evaluation items of preclinical tasks were assessed, and the assessment results from the student, teaching assistant, and tutor were compared. Furthermore, questionnaires were used to evaluate students' experiences with the new system., Results: The tutor, teaching assistant, and students all had similar scorings and high intraclass correlation coefficients (ICC) for mechanical preparation and obturation rubrics, while the students had underestimated scores on the access cavity rubric with a rather low ICC of 0.387, which also lead to the underestimated overall scoring (P < 0.05). Among the 21 evaluation criteria, 9 items were rated statistically different (P < 0.05), which denoted the major deficiencies of students' self-assessments. More than 80% of students rated satisfied for most of the questions regarding the new training system, except the tactile sensation, hardness, and radiopacity., Conclusion: The proposed standardized 3D printed model and structured scoring rubrics is feasible for preclinical endodontic training, and standardized evaluation of students' self-assessment ability., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Purpose: Although YAP1 and TAZ are believed to be equivalent downstream effectors of the Hippo pathway, differential expression of YAP1 or TAZ suggests distinct functions during cancer progression. The exact role of YAP1 and TAZ in esophageal cancer, the 6th leading cancer-related mortality in the world, remains elusive., Methods: Following single or double manipulation of YAP1 or TAZ expression, we subjected these manipulated cells to proliferation, migration, invasion, and xenograft tumorigenesis assays. We used RT-qPCR and Western blotting to examine their expression in the manipulated cells with or without inhibition of transcription or translation. We also examined the impact of YAP1 or TAZ deregulation on clinical outcome of esophageal cancer patients from the TCGA database., Results: We found that YAP1 functions as a tumor suppressor whereas TAZ exerts pro-tumor functions in esophageal cancer cells. We also found a significant increase in TAZ mRNA expression upon YAP1 depletion, but not vice versa, despite the downregulation of CTGF and CYR61, shared targets of YAP1 and TAZ, in xenografted tissue cells. In addition to transcriptional regulation, YAP1-mediated TAZ expression was found to occur via protein synthesis. Restored TAZ expression mitigated YAP1-mediated suppression of cellular behavior. By contrast, TAZ silencing reduced the promoting effect exerted by YAP1 depletion on cellular behaviors. The observed anti-tumor function of YAP1 was further supported by a better overall survival among esophageal cancer patients with a high YAP1 expression., Conclusion: From our data we conclude that YAP1 functions as a suppressor and negatively regulates pro-tumor TAZ expression via transcriptional and translational control in esophageal cancer., (© 2022. The Author(s).)

Collision-induced dissociation tandem mass spectrometry (CID-MS n ) and computational investigation at the MP2/6-311+G(d,p) level of theory have been employed to study Na + -tagged fructose, an example of a ketohexose featuring four cyclic isomers: α-fructofuranose (αFru f ), β-fructofuranose (βFru f ), α-fructopyranose (αFru p ), and β-fructopyranose (βFru p ). The four isomers can be separated by high-performance liquid chromatography (HPLC) and they show different mass spectra, indicating that CID-MS n can distinguish the different fructose forms. Based on a simulation using a micro-kinetic model, we have obtained an overview of the mechanisms for the different dissociation pathways. It has been demonstrated that the preference for the C-C cleavage over the competing isomerization of linear fructose is the main reason for the previously reported differences between the CID-MS spectra of aldohexoses and ketohexoses. In addition, the kinetic modeling helped to confirm the assignment of the different measured mass spectra to the different fructose isomers. The previously reported assignment based on the peak intensities in the HPLC chromatogram had left some open questions as the preference for the dehydration channels did not always follow trends previously observed for aldohexoses. Setting up the kinetic model further enabled us to directly compare the computational and experimental results, which indicated that the model can reproduce most trends in the differences between the dissociation pathways of the four cyclic fructose isomers.

Cerebrospinal fluid (CSF) and its drainage are crucial in clearing metabolic waste and maintaining the microenvironment of the central nervous system for proper functioning. Normal-pressure hydrocephalus (NPH) is a serious neurological disorder of the elderly with obstruction of CSF flow outside the cerebral ventricles, causing ventriculomegaly. The stasis of CSF in NPH compromises brain functioning. Although treatable, often with shunt implantation for drainage, the outcome depends highly on early diagnosis, which, however, is challenging. The initial symptoms of NPH are hard to be aware of and the complete symptoms overlap with those of other neurological diseases. Ventriculomegaly is not specific to NPH as well. The lack of knowledge on the initial stages in its development and throughout its progression further deters early diagnosis. Thus, we are in dire need for an appropriate animal model for researches into a more thorough understanding of its development and pathophysiology so that we can enhance the diagnosis and therapeutic strategies to improve the prognosis of NPH following treatment. With this, we review the few currently available experimental rodent NPH models for these animals are smaller in sizes, easier in maintenance, and having a rapid life cycle. Among these, a parietal convexity subarachnoid space kaolin injection adult rat model appears promising as it shows a slow onset of ventriculomegaly in association with cognitive and motor disabilities resembling the elderly NPH in humans., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Tzu Chi Medical Journal.)