Interpolation-split: a data-centric deep learning approach with big interpolated data to boost airway segmentation performance.

The morphology and distribution of airway tree abnormalities enable diagnosis and disease characterisation across a variety of chronic respiratory conditions. In this regard, airway segmentation plays a critical role in the production of the outline of the entire airway tree to enable estimation of disease extent and severity. Furthermore, the segmentation of a complete airway tree is challenging as the intensity, scale/size and shape of airway segments and their walls change across generations. The existing classical techniques either provide an undersegmented or oversegmented airway tree, and manual intervention is required for optimal airway tree segmentation. The recent development of deep learning methods provides a fully automatic way of segmenting airway trees; however, these methods usually require high GPU memory usage and are difficult to implement in low computational resource environments. Therefore, in this study, we propose a data-centric deep learning technique with big interpolated data, Interpolation-Split, to boost the segmentation performance of the airway tree. The proposed technique utilises interpolation and image split to improve data usefulness and quality. Then, an ensemble learning strategy is implemented to aggregate the segmented airway segments at different scales. In terms of average segmentation performance (dice similarity coefficient, DSC), our method (A) achieves 90.55%, 89.52%, and 85.80%; (B) outperforms the baseline models by 2.89%, 3.86%, and 3.87% on average; and (C) produces maximum segmentation performance gain by 14.11%, 9.28%, and 12.70% for individual cases when (1) nnU-Net with instant normalisation and leaky ReLU; (2) nnU-Net with batch normalisation and ReLU; and (3) modified dilated U-Net are used respectively. Our proposed method outperformed the state-of-the-art airway segmentation approaches. Furthermore, our proposed technique has low RAM and GPU memory usage, and it is GPU memory-efficient and highly flexible, enabling it to be deployed on any 2D deep learning model.

Application of image recognition-based tracker-less augmented reality navigation system in a series of sawbone trials.

BACKGROUND: This study introduced an Augmented Reality (AR) navigation system to address limitations in conventional high tibial osteotomy (HTO). The objective was to enhance precision and efficiency in HTO procedures, overcoming challenges such as inconsistent postoperative alignment and potential neurovascular damage. METHODS: The AR-MR (Mixed Reality) navigation system, comprising HoloLens, Unity Engine, and Vuforia software, was employed for pre-clinical trials using tibial sawbone models. CT images generated 3D anatomical models, projected via HoloLens, allowing surgeons to interact through intuitive hand gestures. The critical procedure of target tracking, essential for aligning virtual and real objects, was facilitated by Vuforia's feature detection algorithm. RESULTS: In trials, the AR-MR system demonstrated significant reductions in both preoperative planning and intraoperative times compared to conventional navigation and metal 3D-printed surgical guides. The AR system, while exhibiting lower accuracy, exhibited efficiency, making it a promising option for HTO procedures. The preoperative planning time for the AR system was notably shorter (4 min) compared to conventional navigation (30.5 min) and metal guides (75.5 min). Intraoperative time for AR lasted 8.5 min, considerably faster than that of conventional navigation (31.5 min) and metal guides (10.5 min). CONCLUSIONS: The AR navigation system presents a transformative approach to HTO, offering a trade-off between accuracy and efficiency. Ongoing improvements, such as the incorporation of two-stage registration and pointing devices, could further enhance precision. While the system may be less accurate, its efficiency renders it a potential breakthrough in orthopedic surgery, particularly for reducing unnecessary harm and streamlining surgical procedures.

First Report of Grovesinia moricola Causing Zonate Leaf Spot on Hernandia nymphaeifolia in Taiwan.

Hernandia nymphaeifolia (C. Presl) Kubitzki, a native tree of Taiwan, is a sea drift plant (Yang and Lu 1996). It is a salt- and wind-tolerant tree (Bezona et al. 2009) and was selected for the afforestation of badlands in coastal areas of Taiwan. In December 2022, all H. nymphaeifolia seedlings at a nursery in Wu-Lai, Taiwan were diseased and wilted with a similar progression. The initial symptom was small zonate white or gray lesions with water-soaked periphery on leaves. Then, expansion and fusion of leaf spots which caused leaf blight and defoliation were observed. Seedlings eventually wilted. Sporophores found on the host were generally hypophyllous, solitary, erect, and easily detachable. The upper portion of the sporophore was considered an individual conidium and consisted of a pyramidal head that was fusiform to ventricose, 206.3 to 501.8 µm (average: 378.0 ± 75.3 µm) long, and 63.6 to 104.5 µm (average: 85.0 ± 16.2 µm) wide at the broadest point (n=30). Branches within the pyramidal head were short, compact, and di- or trichotomously branched. The central stipe was hyaline, broad, septate, tapering toward an acute apex, and sometimes constricted at the basal septum. Sclerotia were gray or black, spherical, and 1.0 to 2.5 mm (n=10) in diameter and observed on older lesions. The fungus was isolated from infected tissue and sporophores and maintained on potato dextrose agar (PDA) at 20°C in darkness. Sclerotia were produced on PDA after 4 to 5 weeks and were irregular or spherical, but no sporophore was developed. The fungus was identified as Grovesinia moricola (I. Hino) Redhead based on morphological characteristics (Tomoko et al. 2006). Three DNA samples was obtained from the cultures isolated from the diseased leaf, sporophores and sclerotia. They were then amplified by PCR with primers for the internal transcribed spacer region (ITS; primers ITS5/ITS4) and the large subunit nuclear ribosomal RNA gene (LSU; primers LR0R/LR5) (Cho et al. 2017), and then sequenced respectively. The sequences were deposited into GenBank with accession nos. PP727191 to PP727193 and PP748518 to PP748520. BLAST analysis of the three isolates showed 100% identity to the sequences of G. moricola from Taiwan (OP550202, OP550203) for the ITS region and 99.9% identity to the sequence of G. moricola from the USA (MW013804) for the LSU rRNA gene. The specimens (FS2022-140) and the culture (Asco-0109) in this study were deposited into the herbarium of Taiwan Forestry Research Institute in Taiwan. Koch's postulates were performed by inoculating four 8-month-old, asymptomatic, potted H. nymphaeifolia plants; every plant was inoculated with sporophores from infected leaves on the upper surface of each of five leaves. Four uninoculated plants were kept in separate pots and served as controls. All plants were covered with transparent plastic bags individually and incubated in a growth chamber at 18 to 20°C with 8 h of light. Similar leaf spots and sporophores were observed after 2 to 4 days and 10 days on every inoculated plant but not on uninoculated plants. The pathogen with a similar colony on PDA was reisolated from the leaf spots of the inoculated plants. Molecular identification of the reisolated pathogen by the above method was carried out. The sequences showed 99.9% identity to the sequence of G. moricola, and were deposited into GenBank with accession nos. PQ157896 to PQ157897 (ITS region) and PQ157701 to PQ157702 (LSU rRNA gene). The pathogenicity test was repeated once. G. moricola is known to cause severe defoliation on woody and annual plants, including at least 73 host species and 36 families distributed in the eastern United States and Japan (Trolinger et al. 1978). This is the first report of G. moricola on H. nymphaeifolia in the world. Control of the disease would play an important role in maintaining healthy seedlings for the afforestation in Taiwan.

Harnessing immunomodulation to combat sarcopenia: current insights and possible approaches.

Sarcopenia is a complex age-associated syndrome of progressive loss of muscle mass and strength. Although this condition is influenced by many factors, age-related changes in immune function including immune cell dynamics, and chronic inflammation contribute to its progression. The complex interplay between the immune system, gut-muscle axis, and autophagy further underscores their important roles in sarcopenia pathogenesis. Immunomodulation has emerged as a promising strategy to counteract sarcopenia. Traditional management approaches to treat sarcopenia including physical exercise and nutritional supplementation, and the emerging technologies of biophysical stimulation demonstrated the importance of immunomodulation and regulation of macrophages and T cells and reduction of chronic inflammation. Treatments to alleviate low-grade inflammation in older adults by modulating gut microbial composition and diversity further combat sarcopenia. Furthermore, some pharmacological interventions, nano-medicine, and cell therapies targeting muscle, gut microbiota, or autophagy present additional avenues for immunomodulation in sarcopenia. This narrative review explores the immunological underpinnings of sarcopenia, elucidating the relationship between the immune system and muscle during ageing. Additionally, the review discusses new areas such as the gut-muscle axis and autophagy, which bridge immune system function and muscle health. Insights into current and potential approaches for sarcopenia management through modulation of the immune system are provided, along with suggestions for future research directions and therapeutic strategies. We aim to guide further investigation into clinical immunological biomarkers and identify indicators for sarcopenia diagnosis and potential treatment targets to combat this condition. We also aim to draw attention to the importance of considering immunomodulation in the clinical management of sarcopenia.

Treatment effects, adverse outcomes and cardiovascular safety of romosozumab - Existing worldwide data: A systematic review and meta-analysis.

Background: Romosozumab is a novel monoclonal antibody that binds to sclerostin, and has dual effects of increasing bone formation and decreasing bone resorption, giving it a unique mechanism of action. The objective of this study was to perform a systematic review and meta-analysis based on existing worldwide data on treatment effects and safety of romosozumab in randomized controlled trials. Methods: A systematic search was carried out on four databases including PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL). The keywords used for search was "(romosozumab) AND (osteoporosis OR safety)". Randomized controlled trial or post-hoc studies of the included randomized controlled trial which studied the effects and safety of romosozumab were included. The quality of selected studies was assessed with the Cochrane collaboration tool and the PEDro scale. Results: 20 studies were included for qualitative analysis. 14 studies were included for meta-analysis. In total, there were 13,507 (n = 13,507) participants with 637 men and 12,870 women from original cohorts. The overall mean difference was in favor of romosozumab treatment for lumbar spine (10.04 (95 % confidence interval (CI) = 7.51-12.57; p < 0.00001)), total hip (4.04 (95 % CI = 3.10-4.99; p < 0.00001)) and femoral neck bone mineral density (3.77 (95 % CI = 2.90-4.64; p < 0.00001)) at 12 months. There was significantly less likelihood of new vertebral fractures with romosozumab compared to control (odds ratio (OR) 0.42 (95 % CI = 0.20-0.89); p = 0.02) at 12 months of treatment. There was significantly less likelihood of new vertebral fracture at 24 months with 12 months of romosozumab followed by sequential treatment with anti-resorptive compared to control with only anti-resorptive agent use (OR 0.36 (95 % CI = 0.18-0.71); p = 0.003). There was no significant difference in serious adverse events and fatal adverse events with use of romosozumab compared with control in our meta-analyses. There were no significant differences in serious cardiovascular events in Asian population of romosozumab with control group with 12 months of romosozumab treatment followed by 24 months of anti-resorptive agent with OR 1.09 (95 % CI = 0.40-2.96; P = 0.86). There was no significant difference between romosozumab group and control group for the median time to radiographic healing. Our qualitative analysis on Quantitative Computed Tomography (QCT), Finite element analysis (FEA) and bone biopsy analyses demonstrated that romosozumab improved parameters and measures in these domains as well. Conclusion: In conclusion, our study showed that romosozumab was an effective agent to treat osteoporosis with high quality evidence. There were no significant differences in the adverse events, serious adverse events, fatal adverse events identified. Further subgroup analysis of cardiovascular events and cardiovascular death in the total population showed no differences either. The translational potential of this article: Given the results, romosozumab is an effective agent to treat patients with very-high risk of osteoporotic fractures.

Comparative Analysis of Mitochondria Surrounding the Intercalated Discs in Heart Diseases-An Ultrastructural Pilot Study.

BACKGROUND: Mitochondria play a crucial role in adapting to fluctuating energy demands, particularly in various heart diseases. This study investigates mitochondrial morphology near intercalated discs in left ventricular (LV) heart tissues, comparing samples from patients with sinus rhythm (SR), atrial fibrillation (AF), dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM). METHODS: Transmission electron microscopy was used to analyze mitochondria within 0-3.5 µm and 3.5-7 µm of intercalated discs in 9 SR, 10 AF, 9 DCM, and 8 ICM patient samples. Parameters included mean size in µm2 and elongation, count, percental mitochondrial area in the measuring frame, and a conglomeration score. RESULTS: AF patients exhibited higher counts of small mitochondria in the LV myocardium, resembling SR. DCM and ICM groups had fewer, larger, and often hydropic mitochondria. Accumulation rates and percental mitochondrial area were similar across groups. Significant positive correlations existed between other defects/size and hydropic mitochondria and between count/area and conglomeration score, while negative correlations between count and size/other defects and between hydropic mitochondria and count could be seen as well. CONCLUSION: Mitochondrial parameters in the LV myocardium of AF patients were similar to those of SR patients, while DCM and ICM displayed distinct changes, including a decrease in number, an increase in size, and compromised mitochondrial morphology. Further research is needed to fully elucidate the pathophysiological role of mitochondrial morphology in different heart diseases, providing deeper insights into potential therapeutic targets and interventions.

Wnt/ß-catenin signaling pathway as an important mediator in muscle and bone crosstalk: A systematic review.

Background: The interaction between muscle and bone is shown to be clinically important but the underlying mechanisms are largely unknown. The canonical Wnt/ß-catenin signaling pathway is reported to be involved in muscle-bone crosstalk, but its detailed function remains unclear. This systematic review aims to investigate and elucidate the role of the Wnt/ß-catenin signaling pathways in muscle-bone crosstalk. Methods: We conducted a literature search on the Web of Science, PubMed, EBSCO and Embase with keywords "Wnt*", "bone*" and "muscle*". A systematic review was completed according to the guideline of preferred reporting items of systematic reviews and meta-analyses (PRISMA). Data synthesis included species (human, animal or cell type used), treatments involved, outcome measures and key findings with respect to Wnts. Results: Seventeen papers were published from 2007 to 2021 and were extracted from a total of 1529 search results in the databases of Web of Science (468 papers), PubMed (457 papers), EBSCO (371) and Embase (233). 12 Wnt family members were investigated in the papers, including Wnt1, Wnt2, Wnt2b, Wnt3a, Wnt4, Wnt5a, Wnt8a, Wnt8b, Wnt9a, Wnt10a, Wnt10b and Wnt16. Many studies showed that muscles were able to increase or decrease osteogenesis of bone, while bone increased myogenesis of muscle through Wnt/ß-catenin signaling pathways. Wnt3a, Wnt4 and Wnt10b were shown to play important roles in the crosstalk between muscle and bone. Conclusions: Wnt3a, Wnt4 and Wnt10b are found to play important mediatory roles in muscle-bone crosstalk. The role of Wnt4 was mostly found to regulate muscle from the bone side. Whilst the role of Wnt10b during muscle ageing was proposed, current evidence is insufficient to clarify the specific role of Wnt/ß-catenin signaling in the interplay between sarcopenia and osteoporosis. More future studies are required to investigate the exact regulatory roles of Wnts in muscle-bone crosstalk in musculoskeletal disease models such as sarcopenia and osteoporosis. Translational potential of this article: The systematic review provides an extensive overview to reveal the roles of Wnt/ß-catenin signaling pathways in muscle-bone crosstalk. These results provide novel research directions to further understand the underlying mechanism of sarcopenia, osteoporosis, and their crosstalk, finally helping the future development of new therapeutic interventions.

Antifungal efficacy of natural antiseptic products against Candida auris.

Candida auris is an emerging fungal pathogen responsible for healthcare-associated infections and outbreaks with high mortality around the world. It readily colonizes the skin, nares, respiratory and urinary tract of hospitalized patients, and such colonization may lead to invasive Candida infection in susceptible patients. However, there is no recommended decolonization protocol for C. auris by international health authorities. The aim of this study is to evaluate the susceptibility of C. auris to commonly used synthetic and natural antiseptic products using an in vitro, broth microdilution assay. Synthetic antiseptics including chlorhexidine, povidone-iodine, and nystatin were shown to be fungicidal against C. auris. Among the natural antiseptics tested, tea tree oil and manuka oil were both fungicidal against C. auris at concentrations less than or equal to 1.25% (v/v). Manuka honey inhibited C. auris at 25% (v/v) concentrations. Among the commercial products tested, manuka body wash and mouthwash were fungicidal against C. auris at concentrations less than or equal to 0.39% (w/v) and 6.25% (v/v) of products as supplied for use, respectively, while tea tree body wash and MedihoneyTM wound gel demonstrated fungistatic properties. In conclusion, this study demonstrated good in vitro antifungal efficacy of tea tree oil, manuka oil, manuka honey, and commercially available antiseptic products containing these active ingredients. Future studies are warranted to evaluate the effectiveness of these antiseptic products in clinical settings.

Candida auris is an emerging superbug fungus that poses a serious threat to global public health. The excellent antifungal efficacy of natural antiseptics and their commercial hygiene products provide new insights into the development of an alternative decolonization regimen against C. auris.

Effects of physical exercise on neuromuscular junction degeneration during ageing: A systematic review.

The neuromuscular junction (NMJ) is a specialized chemical synapse that converts neural impulses into muscle action. Age-associated NMJ degeneration, which involves nerve terminal and postsynaptic decline, denervation, and loss of motor units, significantly contributes to muscle weakness and dysfunction. Although physical training has been shown to make substantial modifications in NMJ of both young and aged animals, the results are often influenced by methodological variables in existing studies. Moreover, there is still lack of strong consensus on the specific effects of exercise on improving the morphology and function of the ageing NMJ. Consequently, the purpose of this study was to conduct a systematic review to elucidate the effects of exercise training on NMJ compartments in the elderly. We conducted a systematic review using PubMed, Embase, and Web of Science databases, employing relevant keywords. Two independent reviewers selected studies that detailed NMJ changes during exercise in ageing, written in English, and available in full text. In total, 20 papers were included. We examined the altered adaptation of the NMJ to exercise, focusing on presynaptic and postsynaptic structures and myofibers in older animals or humans. Our findings indicated that aged NMJs exhibited different adaptive responses to physical exercise compared to younger counterparts. Endurance training, compared with resistance and voluntary exercise regimens, was found to have a more pronounced effect on NMJ structural remodeling, particularly in fast twitch muscle fibers. Physical exercise was observed to promote the formation and maintenance of acetylcholine receptor (AChR) clusters by increasing the recombinant docking protein 7 (Dok7) expression and stabilizing Agrin and lipoprotein receptor-related protein 4 (LRP4). These insights suggest that research on exercise-related therapies could potentially attenuate the progression of neuromuscular degeneration. Translational potential of this article: This systematic review provides a detailed overview of the effects of different types of physical exercise on improving NMJ in the elderly, providing scientific support for the timely intervention of muscle degeneration in the elderly by physical exercise, and providing help for the development of new therapeutic interventions in the future.

Implants coating strategies for antibacterial treatment in fracture and defect models: A systematic review of animal studies.

Objective: Fracture-related infection (FRI) remains a major concern in orthopaedic trauma. Functionalizing implants with antibacterial coatings are a promising strategy in mitigating FRI. Numerous implant coatings have been reported but the preventive and therapeutic effects vary. This systematic review aimed to provide a comprehensive overview of current implant coating strategies to prevent and treat FRI in animal fracture and bone defect models. Methods: A literature search was performed in three databases: PubMed, Web of Science and Embase, with predetermined keywords and criteria up to 28 February 2023. Preclinical studies on implant coatings in animal fracture or defect models that assessed antibacterial and bone healing effects were included. Results: A total of 14 studies were included in this systematic review, seven of which used fracture models and seven used defect models. Passive coatings with bacteria adhesion resistance were investigated in two studies. Active coatings with bactericidal effects were investigated in 12 studies, four of which used metal ions including Ag+ and Cu2+; five studies used antibiotics including chlorhexidine, tigecycline, vancomycin, and gentamicin sulfate; and the other three studies used natural antibacterial materials including chitosan, antimicrobial peptides, and lysostaphin. Overall, these implant coatings exhibited promising efficacy in antibacterial effects and bone formation. Conclusion: Antibacterial coating strategies reduced bacterial infections in animal models and favored bone healing in vivo. Future studies of implant coatings should focus on optimal biocompatibility, antibacterial effects against multi-drug resistant bacteria and polymicrobial infections, and osseointegration and osteogenesis promotion especially in osteoporotic bone by constructing multi-functional coatings for FRI therapy. The translational potential of this paper: The clinical treatment of FRI is complex and challenging. This review summarizes novel orthopaedic implant coating strategies applied to FRI in preclinical studies, and offers a perspective on the future development of orthopaedic implant coatings, which can potentially contribute to alternative strategies in clinical practice.

Prevention of age-related neuromuscular junction degeneration in sarcopenia by low-magnitude high-frequency vibration.

Neuromuscular junction (NMJ) degeneration is one of pathological factors of sarcopenia. Low-magnitude high-frequency vibration (LMHFV) was reported effective in alleviating the sarcopenia progress. However, no previous study has investigated treatment effects of LMHFV targeting NMJ degeneration in sarcopenia. We first compared morphological differences of NMJ between sarcopenic and non-sarcopenic subjects, as well as young and old C57BL/6 mice. We then systematically characterized the age-related degeneration of NMJ in SAMP8 against its control strain, SAMR1 mice, from 3 to 12 months old. We also investigated effects of LMHFV in SAMP8 on the maintenance of NMJ during the onset of sarcopenia with respect to the Agrin-LRP4-MuSK-Dok7 pathway and investigated the mechanism related to ERK1/2 signaling. We observed sarcopenic/old NMJ presented increased acetylcholine receptors (AChRs) cluster fragmentation and discontinuity than non-sarcopenic/young NMJ. In SAMP8, NMJ degeneration (morphologically at 6 months and functionally at 8 months) was observed associated with the sarcopenia onset (10 months). SAMR1 showed improved NMJ morphology and function compared with SAMP8 at 10 months. Skeletal muscle performance was improved at Month 4 post-LMHFV treatment. Vibration group presented improved NMJ function at Months 2 and 6 posttreatment, accompanied with alleviated morphological degeneration at Month 4 posttreatment. LMHFV increased Dok7 expression at Month 4 posttreatment. In vitro, LMHFV could promote AChRs clustering in myotubes by increasing Dok7 expression through suppressing ERK1/2 phosphorylation. In conclusion, NMJ degeneration was observed associated with the sarcopenia onset in SAMP8. LMHFV may attenuate NMJ degeneration and sarcopenia progression by increasing Dok7 expression through suppressing ERK1/2 phosphorylation.

Pattern and prognostic factors for kidney function progression in survivors of children with acute kidney injury: a cohort study.

OBJECTIVE: To examine the pattern of kidney function progression after acute kidney injury (AKI) and identify the associated risk factors. DESIGN: A prospective cohort study was conducted from June 2020 to June 2021 on children aged 1 month to <18 years admitted to the paediatric intensive care unit (PICU). Acute kidney disease (AKD) was defined as AKI persisting from 7 to 90 days after diagnosis. The natural history and prognostic factors of kidney function progression were determined. RESULTS: Among the 253 admissions with a median (IQR) age of 4.9 (9.7) years, the AKI and AKD incidence was 41.9% and 52.2% respectively. The incidence of estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 was 6.7% at 90 days and 11.9% at latest follow-up. Severe and prolonged AKI and higher degree of nephrotoxic medication exposure were associated with AKD development. The severity and duration of AKI and AKD significantly predicted kidney function non-recovery. Children with both entities exhibited a higher peak-to-baseline serum creatinine level ratio at 90 days (1.6 vs 1.0, p<0.001), and a more pronounced decline in eGFR (21% vs 19%, p=0.028) during the follow-up period compared with those without AKI/AKD. They also had an increased risk of having eGFR <90 mL/min/1.73 m2 at 90 days (HR 14.9 (95% CI 1.8 to 124.0)) and latest follow-up (HR 3.8 (95% CI 1.1 to 13.1)). CONCLUSIONS: AKI and AKD are prevalent among critically ill children and pose substantial risk for non-recovery of kidney function among PICU survivors. A structural follow-up visit for AKI survivors to monitor kidney function progression is advocated.

Evaluation of patients treated with direct-acting anti-viral therapy for chronic hepatitis C and their risk of hepatocellular carcinoma in Hong Kong.

BACKGROUND & AIM: To evaluate the risk of early hepatocellular carcinoma (HCC) in chronic hepatitis C patients treated with direct-acting antivirals (DAAs) in Hong Kong, as it has not been studied before in this locality. METHODS: Three hundred thirty-three consecutive chronic hepatitis C patients treated with DAAs from two hospitals over the past 6 years were identified. Kaplan-Meier method was used to calculate cumulative HCC incidence. Cox regression was used to identify factors associated with HCC development. RESULTS: During a median follow-up of 23.4 months after DAA started, 15 (5.4%, 95% CI 3.3-8.7%) out of 279 total included patients developed HCC. The overall sustained virological response (SVR) rate was 98.9%. The 1-year cumulative incidence for de-novo HCC and HCC recurrence were 0.8 and 30.9%, respectively (log-rank test p < 0.001). The 1-year cumulative HCC incidence for patients without and with cirrhosis were 0.7 and 5.1%, respectively (log-rank test p = 0.036). Univariate analysis showed that significant factors associated with HCC after DAA were: history of treated HCC, cirrhosis, evidence of portal hypertension, higher AFP at the start or end of DAA therapy, higher bilirubin, lower platelets, lower albumin, and older age. From receiver operating characteristic curve analysis, the optimal cut-off level of AFP for predicting HCC was 10.5 ng/mL at the start and 5.6 ng/mL at the end of DAA therapy. CONCLUSIONS: The risk of early HCC recurrence remains high despite achieving SVR following DAA therapy, whereas the risk of early de-novo HCC occurence is low. AFP levels, both at the start and end of DAA therapy, can be useful in stratifying risks of HCC development.

Pancultural nostalgia in action: Prevalence, triggers, and psychological functions of nostalgia across cultures.

Nostalgia is a social, self-relevant, and bittersweet (although mostly positive) emotion that arises when reflecting on fond past memories and serves key psychological functions. The majority of evidence concerning the prevalence, triggers, and functions of nostalgia has been amassed in samples from a handful of largely Western cultures. If nostalgia is a fundamental psychological resource, it should perform similar functions across cultures, although its operational dynamics may be shaped by culture. This study (N = 2,606) examined dispositional nostalgia, self-reported triggers of nostalgia, and functions of experimentally induced nostalgia in young adults across 28 countries and a special administrative region of China (i.e., Hong Kong). Results indicated that nostalgia is frequently experienced across cultures, albeit better valued in more-developed countries (i.e., higher national wealth and life-expectancy). Nostalgia is triggered by psychological threats (especially in warmer countries), sensory stimuli (especially in more-developed countries), and social gatherings (especially in less-developed countries). The positive or negative affect prompted by experimentally induced nostalgia varied by country, but was mild overall. More importantly, recalling a nostalgic (vs. ordinary) memory increased social connectedness, self-continuity, and meaning in life across cultures. In less-developed countries, recalling an ordinary memory also conferred some of these functions, reducing the effect size of nostalgia. Finally, recalling a nostalgic (vs. ordinary) memory augmented state satisfaction with life in countries with lower quality of living (i.e., lower life-expectancy and life-satisfaction). Overall, findings confirm the relevance of nostalgia across a wide range of cultures and indicate cultural nuances in its functioning. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Biophysical and nutritional combination treatment for myosteatosis in patients with sarcopenia: a study protocol for single-blinded randomised controlled trial.

INTRODUCTION: Sarcopenia is characterised by age-related loss of skeletal muscle and function and is associated with risks of adverse outcomes. The prevalence of sarcopenia increases due to ageing population and effective interventions is in need. Previous studies showed that ß-hydroxy ß-methylbutyrate (HMB) supplement and vibration treatment (VT) enhanced muscle quality, while the coapplication of the two interventions had further improved muscle mass and function in sarcopenic mice model. This study aims to investigate the efficacy of this combination treatment in combating sarcopenia in older people. The findings of this study will demonstrate the effect of combination treatment as an alternative for managing sarcopenia. METHODS AND ANALYSIS: In this single-blinded randomised controlled trial, subjects will be screened based on the Asian Working Group for Sarcopenia (AWGS) 2019 definition. 200 subjects who are aged 65 or above and identified sarcopenic according to the AWGS algorithm will be recruited. They will be randomised to one of the following four groups: (1) Control+ONS; (2) HMB+ONS; (3) VT+ONS and (4) HMB+VT + ONS, where ONS stands for oral nutritional supplement. ONS will be taken in the form of protein formular once/day; HMB supplements will be 3 g/day; VT (35 Hz, 0.3 g, where g=gravitational acceleration) will be received for 20 mins/day and at least 3 days/week. The primary outcome assessments are muscle strength and function. Subjects will be assessed at baseline, 3-month and 6-month post treatment. ETHICS AND DISSEMINATION: This study was approved by Joint CUHK-NTEC (The Chinese University of Hong Kong and New Territories East Cluster) Clinical Research Management Office (Ref: CRE-2022.223-T) and conformed to the Declaration of Helsinki. Trial results will be published in peer-reviewed journals and disseminated at academic conferences. TRIAL REGISTRATION NUMBER: NCT05525039.

The impact of tubular dysfunction and its relationship with acute kidney injury in children.

BACKGROUND: Tubular dysfunction can cause electrolyte disturbances with potentially serious consequences. We studied the epidemiology and outcomes of electrolyte disturbances and tubular dysfunction among critically ill children and evaluated their relationships with acute kidney injury (AKI). METHODS: We conducted a prospective cohort study recruiting children aged 1 month to ≤ 18 years old admitted to the pediatric intensive care unit (PICU) from 6/2020 to 6/2021. The serum levels of sodium, potassium, calcium, phosphate, and magnesium were reviewed and simultaneous urinary investigations for tubular function were performed among children with electrolyte disturbances. RESULTS: Altogether there were 253 episodes of admission. The median (interquartile) age was 4.9 (1.3-11.0) years and 58.1% were male. The median number of electrolyte disorders was 3 (2-4) types. Hypophosphatemia (74.2%), hypocalcemia (70.3%) and hypermagnesemia (52.9%) were the three commonest types of disturbances. Urinary electrolyte wasting was commonly observed among children with hypomagnesemia (70.6%), hypophosphatemia (67.4%) and hypokalemia (28.6%). Tubular dysfunction was detected in 82.6% of patients and urinary ß2-microglobulin level significantly correlated with the severity of tubular dysfunction (p < 0.001). The development of tubular dysfunction was independent of AKI status. Tubular dysfunction was associated with mortality (p < 0.001) and was an independent predictor of PICU length of stay (LOS) (p < 0.001). The incorporation of the tubular dysfunction severity into the AKI staging system improved the prediction of PICU LOS. CONCLUSIONS: Tubular dysfunction was associated with both morbidity and mortality in critically ill children and its assessment may help to capture a more comprehensive picture of acute kidney insult.

COVID-19 hip fracture outcomes: The role of Ct values and D-dimer levels?

Introduction: The COVID-19 pandemic has caused high mortality rates in hip fracture patients, but data for Asian patients are lacking. Whilst Cycle threshold (Ct) values and D-dimer have been reported as predictors of mortality in COVID-19 patients, their prognostic roles in those with concomitant hip fracture remain unknown. The objectives of this study were to i) assess the clinical outcomes of COVID-19 hip fractures patients in the Chinese population, ii) identify risk factors of mortality and complications, and iii) determine the prognostic roles of Ct values and D-dimer levels. Methodology: This cohort study was conducted during the 5th wave of the COVID-19 pandemic. Inclusion criteria were 1) hip fracture 2) â€‹≥ â€‹60 years old 3) low-energy trauma. Outcomes were 90-day all-cause mortality, complications, length of stay, discharge destination and mobility status. Logistic regression analysis was performed to identify risk factors for mortality and complications. Subgroup analysis was performed for patients with Ct â€‹< â€‹30 and Ct â€‹> â€‹30, comparing their outcomes of operations performed within 48 â€‹h vs beyond 48 â€‹h. Results: 159 hip fracture patients were included, 42 patients were COVID-19 positive. COVID-19 group had significantly higher 90-day mortality rates (21.4% vs 9.4%), complication rates (45.2% vs 28.2%) and longer length of stay (17.06 vs 10.84 nights). COVID-19 was an independent risk factor for mortality and complications. Amongst the COVID-19 group, risk factors for poor outcomes were advanced age, steroids use, conservative treatment and American Society of Anaesthesiologists (ASA) score ≥ 3. Conservative treatment was associated with higher mortality (OR â€‹= â€‹16.00; p â€‹= â€‹0.025) in COVID-19 hip fracture patients. There was no significant difference between Ct values â€‹< â€‹30 and >30 regarding mortality and complication rate. D-dimer and timing to operation did not affect outcomes. Conclusions: Patients with concomitant COVID-19 and hip fracture are at high risk of mortality and complications. Ct values and D-dimer levels have no prognostic roles for hip fracture outcomes. Early operative treatment is recommended as soon as patients are medically fit.

An early glycolysis burst in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuroinflammation.

Metabolism and energy processes governing oligodendrocyte function during neuroinflammatory disease are of great interest. However, how varied cellular environments affect oligodendrocyte activity during neuroinflammation is unknown. We demonstrate that activated microglial energy metabolism controls oligodendrocyte mitochondrial respiration and activity. Lipopolysaccharide/interferon gamma promote glycolysis and decrease mitochondrial respiration and myelin protein synthesis in rat brain glial cells. Enriched microglia showed an early burst in glycolysis. In microglia-conditioned medium, oligodendrocytes did not respire and expressed less myelin. SCENITH revealed metabolic derangement in microglia and O4-positive oligodendrocytes in endotoxemia and experimental autoimmune encephalitogenic models. The early burst of glycolysis in microglia was mediated by PDPK1 and protein kinase B/AKT signaling. We found that microglia-produced NO and itaconate, a tricarboxylic acid bifurcated metabolite, reduced mitochondrial respiration in oligodendrocytes. During inflammation, we discovered a signaling pathway in microglia that could be used as a therapeutic target to restore mitochondrial function in oligodendrocytes and induce remyelination.

Application of algorithmic cytomorphological assessment and immunocytochemistry with the international system for reporting serous fluid cytopathology on pericardial fluid cytology.

AIMS: The international system for reporting serous fluid cytopathology (ISRSFC) set forth a five-tiered reporting system with comprehensive validation on pleural and peritoneal fluid cytology. An algorithmic approach for cytomorphological assessment and immunocytochemistry was also described in ISRSFC. Limited data on pericardial fluid are supportive but would benefit from further investigation. METHODS: Consecutive pericardial fluid cytology over a 4-year period was reviewed by multiple board-certified pathologists according to the ISRSFC. Cytomorphology and immunocytochemistry were assessed sequentially, with respective diagnostic performances computed and compared. Literature review was performed. RESULTS: In total 358 specimens, including 53 with immunocytochemistry available, were reviewed. There were 137 benign and 221 malignant (MAL) cases. The risks of malignancy were 23.5% non-diagnostic (ND), 29.2% negative for malignancy (NFM), 56.0% atypia of undetermined significance (AUS), 82.6% suspicious for malignancy (SFM) and 99.2% (MAL) for cytomorphological assessment, improving to 23.5% (ND), 29.1% (NFM), 56.8% (AUS), 78.9% (SFM) and 99.3% (MAL) incorporating immunocytochemistry. Ten cases (2.8%) received a change in diagnosis after review of immunocytochemistry. All revisions of diagnostic category were appropriate upgrades/downgrades referenced against clinical information. Cytomorphological typing was accurate for adenocarcinoma (n=81/83, 97.6%), while other carcinomas and lymphomas required immunocytochemistry. Certain subcategories within AUS and SFM pertaining to bland indeterminate epithelial cells or mucinous material were not seen for pericardial fluid. CONCLUSIONS: The ISRSFC shows robust diagnostic performance for pericardial fluid cytology. For pericardial effusion, disease composition and applicable cytological subcategories differ from its peritoneal and pleural counterparts. Incorporating immunocytochemistry by an algorithmic approach improves diagnostic accuracy. Cytomorphology is accurate for identifying adenocarcinomas, but further typing necessitates immunocytochemistry is necessary.

Potential of Fatty Acids in Treating Sarcopenia: A Systematic Review.

This paper presents a systematic review of studies investigating the effects of fatty acid supplementation in potentially preventing and treating sarcopenia. PubMed, Embase, and Web of Science databases were searched using the keywords 'fatty acid' and 'sarcopenia'. Results: A total of 14 clinical and 11 pre-clinical (including cell and animal studies) studies were included. Of the 14 clinical studies, 12 used omega-3 polyunsaturated fatty acids (PUFAs) as supplements, 1 study used ALA and 1 study used CLA. Seven studies combined the use of fatty acid with resistant exercises. Fatty acids were found to have a positive effect in eight studies and they had no significant outcome in six studies. The seven studies that incorporated exercise found that fatty acids had a better impact on elderlies. Four animal studies used novel fatty acids including eicosapentaenoic acid, trans-fatty acid, and olive leaf extraction as interventions. Three animal and four cell experiment studies revealed the possible mechanisms of how fatty acids affect muscles by improving regenerative capacity, reducing oxidative stress, mitochondrial and peroxisomal dysfunctions, and attenuating cell death. Conclusion: Fatty acids have proven their value in improving sarcopenia in pre-clinical experiments. However, current clinical studies show controversial results for its role on muscle, and thus the mechanisms need to be studied further. In the future, more well-designed randomized controlled trials are required to assess the effectiveness of using fatty acids in humans.