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Kuo-Hsuan Hung,1– 3 Yu-Hsiang Lan,2,4 Jui-Yen Lin,1,2 Eugene Yu-Chuan Kang,1,2 Hsin-Yuan Tan,1,2 Hung-Chi Chen,1,2 Ching-Hsi Hsiao,1,2 Lung-Kun Yeh1,2 1Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan, 333, Taiwan; 2Chang-Gung University, College of Medicine, Taoyuan 333, Taiwan; 3Institute of Clinical Medicine, National Yang-Ming University, Taipei City 112, Taiwan; 4Department of Medicine, Chang Gung University, Taoyuan 333, TaiwanCorrespondence: Lung-Kun YehDepartment of Ophthalmology, Chang Gung Memorial Hospital, Linkou, No 5, Fusing St., Taoyuan 333, TaiwanTel +886-3-3281200, ext. 8666Fax +886-3-3287798Email yehlungkun@gmail.comPurpose: To evaluate the role of Demodex infestation of the eyelids in patients with recurrent herpetic keratitis.Patients and Methods: This is a retrospective and noncomparative case series. Twenty-seven patients with ocular demodicosis and recurrent herpetic keratitis under conventional treatments were enrolled. Demographic data and clinical photographs were collected. Ocular demodicosis was confirmed by eyelash examination under a microscope. Eyelid scrub was initiated in these patients after proving Demodex infestation. Response after treatment was reviewed.Results: Herpetic keratitis was characterized by epithelial defect, including dendritic lesions (seven eyes, 25.9%), geographic ulcer (three eyes, 11.1%), and neurotrophic ulcer (two eyes, 7.4%), associated with stromal involvement in 12 cases. Six cases with stromal reactivation, including disciform keratitis (two eyes, 7.4%), immune ring (three eyes, 11.1%), and ghost vessel (one eye, 3.7%), presented no epithelial defect. Active anterior uveitis with keratic precipitates was found in 15 cases. Demodex blepharitis was diagnosed with cylindrical dandruff along their lashes in all patients. Other ocular findings include meibomian gland dysfunction (15 eyes, 55.6%), mal-aligned lashes (eight eyes, 29.6%), telangiectasia (14 eyes, 51.9%), conjunctivitis (18 eyes, 66.7%), and ocular rosacea (three eyes, 11.1%). Initial unstable clinical presentations showed deterioration of corneal melting into descemetocele, corneal perforation, recalcitrant stromal infiltration/uveitis, and uncontrollable IOP, despite antiherpetic medication. After treatment of Demodex blepharitis, infestation was under control, followed by subjective improvement of ocular symptoms and a stable clinical outcome.Conclusion: Ocular demodicosis should be considered in patients with unstable recurrent herpetic keratitis. A prompt diagnosis and appropriate treatment may curb the progression of herpetic corneal infection.Keywords: blepharitis, Demodex mites, herpetic keratitis, ocular demodicosis

Multifocal fatty liver nodules can present a diagnostic challenge due to their resemblance to metastatic liver disease. This case report illustrates the complexity of such scenarios through the presentation of a middle-aged male patient. Despite the common nature of fatty liver disease, characterized by hepatocyte fat accumulation leading to diffuse and uniform liver lesions, rare instances exhibit heterogeneous appearances. The case underlines the potential confusion arising from imaging modalities when multiple small nodules disperse throughout the liver, mimicking multifocal tumors or metastases. The report emphasizes the critical role of comprehensive diagnostic procedures in preventing misdiagnosis and unwarranted interventions. Effective management hinges on multidisciplinary collaboration among specialists, ensuring accurate differentiation and appropriate treatment. This study serves as a reminder of the intricacies involved in interpreting multifocal fatty liver nodules that may masquerade as metastatic disease, highlighting the need for precision in clinical practice.

This article presents a length-dependent deep neural network (LD-DNN) based channel modeling methodology to predict the frequency response of high-speed channels. The proposed method significantly enhances the model accuracy and design efficiency while considering the channel length dependence that was neglected in previous modeling approaches. We define the concept of the electrical length to model the length and frequency dependence, then further leverage the activation function to capture the multiple reflection effects to improve accuracy. Additionally, we model the insertion loss resonance induced by crosstalk that can seriously deteriorate signal integrity. As a result, by adopting the proposed model which can predict the S-parameters as a function of length, the need for performing additionally 3D electromagnetic simulations when adjusting the channel length can be eliminated. Various high-speed channel cases are tested to validate the accuracy of the proposed method. The modeling accuracy is less than 4% for different high-speed channel structures with run times of less than 1.4 second per design.

In this paper, we present a distributed privacy-preserving quadratic optimization algorithm to solve the Security Constrained Optimal Power Flow (SCOPF) problem in the smart grid. The SCOPF problem seeks the optimal dispatch subject to a set of postulated constraints under the normal and contingency conditions. However, due to the large problem size and real-time requirement, a fast and robust technique is required to solve this problem. Moreover, due to privacy concerns, it is important that the data remains confidential and processed on local computers. Therefore, a fully privacy-preserving algorithm is proposed which performs computation directly over the encrypted SCOPF problem. The SCOPF is decomposed into smaller subproblems corresponding to individual pre-contingency and post-contingency cases using the Alternating Direction Method of Multipliers (ADMM) and gradient projection algorithms. Both algorithms are presented for solving the SCOPF problem in a privacy-preserving and distributed manner. Security analysis shows that our algorithm can preserve both system confidentiality and data privacy. Performance evaluations validate the correctness and effectiveness of the proposed algorithm.

In this paper, we propose an efficient design methodology for energy-efficient off-chip interconnect. This approach leverages an artificial neural network (ANN) as a surrogate model that significantly improves design efficiency in the frequency-domain. This model utilizes design specifications as the constraint functions to guarantee the satisfaction of design requirements. Additionally, a specified objective function to select low-loss and low-noise structure is employed to determine the optimal case from a large design space. The proposed design flow can find the optimum design that gives maximum eye height (EH) with the largest allowable transmitter supply voltage (VTX) reduction for minimum power consumption. The proposed approach is applied to the microstrip line and stripline structures with single-ended and differential signals for general applicability. For the microstrip line, the proposed methodology performs at a performance speed with 42.7 and 0.5 s per structure for the data generation and optimization process, respectively. In addition, the optimal microstrip line design achieves a 25%VTX reduction. In stripline structures, it takes 31.9 s for the data generation and 0.6 s for the optimization process per structure when the power efficiency reaches a maximum 30.7% peak to peak VTX decrease.

Ban Lim area, Caobang province has proposed high potential of lead-zinc resources, which have occurred in different geological formations. In this paper, based on the collecting, synthetics and processing geological data, especially applied mathematical methods to recognize studied objects of exploration process and quantitative description. The results show that the lead-zinc orebodies in Ban Lim area are mainly occurred in lens-shaped and distributed in layered surfaces of dolomitized limestone of Coc Xo formation. The average lead-zinc content of the orebodies is in a range from 3.27% to 8.33%, its coefficient of variation (Vc) is in a range from 13.71% (evenly) to 137.92% (very unevenly). On the whole, the lead-zinc contents of the orebodies in Ban Lim area mainly comply with the standard normal distribution. The average thicknesses of the orebodies are in a range from 0.92 m to 6.48 m, its coefficient of variation (Vm) is in the range from 8.7% (stable) to 132.95% (very unstable). Quantitative calculation results have shown that Ban Lim lead-zinc deposit belongs to group III of deposits. For the exploration of this type of minerals, it is recommended to use linear grid pattern. Appropriate exploration grid pattern for category 122 reserve is (60-80)×(30-40) m.

This study leverages accelerated reactions at the solution/air interface of microdroplets generated by desorption electrospray ionization (DESI) to explore the chemical space. DESI is utilized to synthesize drug analogs at an overall rate of 1 reaction mixture per second, working on the low-nanogram scale. Transformations of multiple drug molecules at specific functionalities (phenol, hydroxyl, amino, carbonyl, phenyl, thiophenyl, and alkenyl) are achieved using electrophilic/nucleophilic, redox, C-H functionalization, and coupling reactions. These transformations occur under ambient conditions on the millisecond time scale with direct detection of products being successful in all but three of the reaction types studied. The large scope (22 bioactive compounds, >20 chemical transformations, and >300 functionalization reagents) and high speed (>3000 reactions/hour) provide access to a wide array of drug analogs that can be used for bioactivity testing. A total of ∼6800 unique reactions were examined through a data-driven workflow, and more than 3000 unique derivatives (∼44%) were identified tentatively by the m / z value and signal-to-control ratio in single-stage mass spectrometry (MS) analysis, with over 1000 being further characterized by tandem MS. The speed of the DESI-MS reaction screen provides potential advantages for emerging machine learning-based predictions of organic synthesis, and it sets the stage for future online DESI-MS bioassays and scaled-up microdroplet synthesis before formal characterization of hit compounds is sought using traditional methods of drug discovery.

Falls are a significant health risk in older adults, and forward and backward falls each account for more than 40 % of falls. Dynamic stability, limb support, and impact energy absorption are crucial balance regulatory components and likely vary with the direction of imbalance. Understanding how perturbation direction influences these key components of balance stability regulation is crucial. This study investigated the balance stability, lower limb impact energy absorption, and limb support in forward and backward directions of balance perturbations in younger versus older adults. Thirteen healthy old and thirteen healthy young adults participated in this study. Participants stood on two adjacent perturbation platforms in modified tandem stance. The leading or trailing limb support surface dropped 76.2 mm vertically at an unknown time to impose body shift. Two-way (direction X group) mixed ANOVA was performed to analyze the anterior margin of stability (MoS), trunk angular displacement, peak negative power at the hip, knee, and ankle, and the peak vertical ground reaction forces (VGRF). Compared to forward perturbation, backward perturbation induced greater MoS (P < 0.01), peak VGRF (P < 0.01), and peak ankle (P < 0.05) and hip (P < 0.05) joint power. Older adults showed decreased MoS (P < 0.05), perturbed limb peak VGRF (P < 0.05), and ankle (P < 0.05) and knee (P < 0.05) joint peak power compared to younger adults. Forward perturbations induced greater challenges for dynamic stability, possibly due to trunk motion characteristics, while backward perturbations posed challenges in limb support and impact energy absorption. In addition, age-related deficits in balance stability regulation were observed in both perturbation directions., Competing Interests: Declaration of competing interest None., (Published by Elsevier B.V.)

Cocrystallization has emerged as a promising formulation strategy for modulating transdermal drug absorption by enhancing solubility and permeability. However, challenges related to cocrystal dissociation in the semi-solid state need to be addressed to mitigate regulatory concerns before the widespread implementation of topical cocrystal products in clinical practice. This study aimed to develop oil-based topical formulations incorporating cocrystals with distinct thermodynamic stabilities, followed by investigating the roles of different structurally similar coformers and oily vehicles on their physicochemical properties. Three pharmaceutical cocrystals of poorly water-soluble flufenamic acid (FFA) were synthesized with isomeric pyridine carboxamides in a 1:1 stoichiometry via rapid solvent removal. These included the reported flufenamic acid-nicotinamide cocrystal (FFA-NIC), the long-elusive flufenamic acid-isonicotinamide cocrystal (FFA-IST) and flufenamic acid-picolinamide cocrystal (FFA-PIC). The resulting cocrystals, which exhibited different hydrogen bonding patterns, were characterized using powder X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy, and structural analysis through single crystal X-ray diffraction. The cocrystals were further formulated in a series of oleaginous and absorption bases, including liquid paraffin, Vaseline, lanolin, and theobroma oil, for topical delivery. The cocrystal dissociation, content uniformity, and in vitro membrane diffusion were assessed. Notably, although all FFA cocrystals exhibited thermodynamic instability in aqueous solution, a significantly reduced propensity for cocrystal dissociation was observed in the ointment bases. Integrated computational analyses of packing efficiency and interaction energy revealed that the thermodynamic stability of cocrystals followed a descending order of FFA-NIC > FFA-PIC > FFA-IST. Compared with raw FFA, FFA-IST and FFA-PIC, which had larger positive ΔV non-H and ΔE cocryst , achieved superior cumulative diffusion of FFA from Vaseline, with a 4.3-fold (p = 0.0003) and 3.3-fold (p = 0.0029) increase at 6 h in a Franz diffusion cell model, respectively. The diffusion of all FFA cocrystals mainly followed the Higuchi kinetic model and was positively correlated with the intrinsic dissolution rate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Glucose can activate the carbohydrate response element binding protein (ChREBP) transcription factor to control gene expressions in the metabolic pathways. The way of ChREBP involvement in human prostate cancer development remains undetermined. This study examined the interactions between prostate fibroblasts and cancer cells under the influences of ChREBP. Results showed that high glucose (30 mM) increased the phosphorylation of AKT at S473 and AMP-activated protein kinase (AMPK) at S485 in human prostate fibroblast (HPrF) cells and prostate cancer PC-3 cells. High glucose enhanced the expression of ChREBP, which increased the expressions of fibronectin, alpha-smooth muscle actin (α-SMA), and WNT1 inducible signaling pathway protein 1 (WISP1), magnifying the cell growth and contraction in HPrF cells in vitro. The cell proliferation, invasion, and tumor growth in prostate cancer PC-3 cells were enhanced by inducing the expressions of ChREBP, mucosa-associated lymphoid tissue 1 (MALT1), and epithelial-mesenchymal transition markers with high glucose treatment. Moreover, ectopic ChREBP overexpression induced NF-κB signaling activities via upregulating MALT1 expression in PC-3 cells. Our findings illustrated that ChREBP is an oncogene in the human prostate. High glucose condition induces a glucose/ChREBP/MALT1/NF-κB axis which links the glucose metabolism to the NF-κB activation in prostate cancer cells, and a glucose/ChREBP/WISP1 axis mediating autocrine and paracrine signaling between fibroblasts and cancer cells to promote cell migration, contraction, growth, and invasion of the human prostate., (© 2024 Wiley Periodicals LLC.)

Abutment screw loosening is the most common complication in single implant-supported crowns, typically remedied by simply reattaching the restoration, preferably using a new abutment screw. The internal aspect of the implant along with any other components should be decontaminated before reconnection. This clinical report provides information on the appropriate management of the decontamination process, as well as evidence of the foreign material found within the implant body., (Copyright © 2024 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Background: Acupuncture is a promising modality in clinical practice, where the participants' experiences are crucial to acupuncture's use and effects. However, a comprehensive review synthesising participant experiences throughout treatment sessions is lacking. This study aims to explore the qualitative literature regarding participants' experiences of acupuncture as a potential treatment modality., Methods: A qualitative systematic review of existing literature was conducted through AMED, MEDLINE, Scopus, Embase, and Web of Science. The Joanna Briggs Institute (JBI) critical appraisal checklist was employed to evaluate research quality. Subsequently, the data were extracted and synthesised utilising the JBI Qualitative Assessment and Review Instrument (QARI) tool and data synthesis was carried out through meta-aggregation., Results: A total of twenty-eight articles were incorporated into the analysis. Four synthesised findings were identified: (1) Before acupuncture: last trust and hope; (2) During acupuncture: relaxing and calming; (3) After acupuncture: mind-body effects; and (4) Practitioner-participant relationship., Conclusion: The findings highlight the changes participants experienced before and after acupuncture sessions. Implementing additional promotional initiatives for acupuncture can increase public awareness and encourage individuals to consider it an early symptom management option., Review Registration: This review was registered in PROSPERO (No. CRD42023475373)., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Acute stroke significantly increases the risk of long-term care facility (LTCF) admission, due to sudden functional impairments. This study aims to identify risk factors associated with LTCF admission among stroke patients, specifically targeting those who transitioned from independence to disability after stroke., Patients and Methods: We retrospectively enrolled 2027 stroke patients admitted between 2017 and 2022 from the Chi Mei Medical Center's stroke registry in Southern Taiwan, focusing on those with pre-stroke modified Rankin Scale (mRS) scores ≤ 2 and post-stroke mRS scores ≥ 3. Patients were categorized into LTCF and non-LTCF groups. Stroke severity, comorbidities, and discharge outcomes were evaluated, using logistic regression analyses to identify LTCF admission risk factors., Results: Of the 2027 patients, 343 (16.9%) were admitted to LTCFs post-discharge. The LTCF group exhibited higher discharge mRS and National Institute of Health Stroke Scale scores, and lower Barthel Index scores. Factors linked to LTCF admission included higher discharge mRS scores, lower Barthel Index scores, nasogastric tube placement at discharge, and longer hospital stays. Barthel Index scores showed no significant change from admission to discharge in the LTCF group., Conclusion: Stroke severity, post-stroke functional status and nasogastric tube placement are significant predictors of LTCF admission in stroke patients. Early recognition of these factors is crucial for effective discharge planning and reducing the need for institutionalization. The study emphasizes the need for personalized interventions targeting these risk factors to improve patient outcomes and optimize medical resource utilization., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Lu et al.)

Growing an ultrathin hybrid organic-inorganic perovskite film while maintaining high efficiency and addressing photostability challenges for commercial devices remains a significant hurdle. In this study, we explore the incorporation of organometallic copper phthalocyanine (CuPc) and MS-OC (a previously published spiro-based interfacial material for perovskite solar cells (PSCs), featuring an ortho-oriented carbazole donor) as an addition to the hole-transporting layer (HTL) in all-vacuum-deposited Cs 0.06 FA 0.94 Pb(I 0.68 Br 0.32 ) 3 PSCs. By innovatively introducing a 3 nm-thin MS-OC layer at the CuPc-perovskite interface, we achieve a deeper understanding of the crystallographic dynamics of perovskites, resulting in a uniform and pinhole-free film. We demonstrate that PSCs utilizing the CuPc HTL with an MS-OC interfacial layer in a p-i-n architecture achieve a power conversion efficiency (PCE) of up to 14.42%. Remarkably, the CuPc/ MS-OC -based device exhibits outstanding long-term photostability, maintaining its initial PCE over 400 h ( T 100 = 400 h) under continuous sunlight illumination. By configuring the device architecture as ITO/MoO 3 /CuPc/ MS-OC /perovskite/C 60 /BCP/Ag, we find that the evaporated MS-OC thin films effectively reduce nonradiative losses, passivate the perovskite, and enhance device performance. Our findings indicate that the polarity of the underlying surface significantly influences perovskite nucleation, underscoring the potential to improve photostability by controlling interfacial imperfections.

To evaluate the relationship between serum gamma-glutamyl transferase (GGT) levels and fatty pancreas in subjects with concurrent obesity, insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD) without a history of pancreatitis. From March 2019 to September 2021, 31 adult subjects with concurrent obesity and MASLD were recruited as part of the study investigating the biological impact of bariatric surgery and lifestyle modification on obesity. Chemical shift encoded MRI of the abdomen, LiverMultiScan, anthropometric, clinical and blood biochemistry analyses were performed prior to any intervention at baseline. GGT (p <.001) was significantly different between those 'with fatty pancreas' and 'without fatty pancreas' groups. GGT (p <.001) was significantly different between those 'with both metabolic syndrome and fatty pancreas' and those 'with metabolic syndrome but without fatty pancreas.' GGT (p <.001) was also significantly different between those 'with both diabetes and fatty pancreas' and those 'with diabetes but without fatty pancreas'. Logistic regression analysis showed that abnormal GGT levels (p = .010) and Hypertension (p = .045) were significant independent predictors of fatty pancreas. GGT was associated with fatty pancreas by an odds ratio 7.333 (95% [CI]: 1.467-36.664), while the AUROC of GGT in determining fatty pancreas was 0.849. Elevation in serum GGT might be a potential marker to identify fatty pancreas., (© 2024 The Author(s). Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Competing Interests: Disclosure The authors have stated that they have no conflicts of interest.

Background: Metabolic dysfunction associated steatotic liver disease (MASLD) is associated with increased cardiovascular disease (CVD) risk in persons with HIV (PWH). The lipidomic and metabolomic alterations contributing to this risk are poorly understood. We aimed to characterize the advanced lipoprotein and targeted metabolomic profiles in PWH and assess if the presence and severity of MASLD influence these profiles., Methods: This is a cross-sectional analysis of a prospectively enrolled multicenter cohort. PWH without alcohol abuse or known liver disease underwent vibration-controlled transient elastography for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Lipidomic and metabolomic profiling was undertaken with nuclear magnetic resonance (NMR) spectroscopy. Hepatic steatosis was defined as CAP ≥ 263 dB/m and clinically significant fibrosis (CSF) as LSM ≥ 8 kPa. Logistic regression models assessed associations between MASLD, CSF and lipidomic and metabolic parameters., Results: Of 190 participants (71% cisgender male, 96% on antiretroviral therapy), 58% had MASLD and 12% CSF. Mean (SD) age was 48.9 (12.1) years and body mass index (BMI) 29.9 (6.4) kg/m 2 . Compared to PWH without MASLD (controls), PWH with MASLD had lower HDL-C but higher total triglyceride, VLDL-C, branched-chain amino acids, GlycA, trimethylamine N-oxide levels, Lipoprotein-Insulin Resistance and Diabetes Risk Indices. There were no significant differences in these parameters between participants with MASLD with or without CSF. In a multivariable regression analysis, MASLD was independently associated with changes in most of these parameters after adjustment for age, gender, race/ethnicity, type 2 diabetes mellitus, BMI, and lipid lowering medications use., Conclusions: MASLD in PWH is independently associated with altered advanced lipoprotein and targeted metabolic profiles, indicating a higher CVD risk in this population., (© 2024. The Author(s).)

With the increasing demand for ammonia applications, there is a significant focus on improving NH 3 detection performance at room temperature. In this study, we introduce a groundbreaking NH 3 gas sensor based on Cu(I)-based coordination polymers, featuring semiconducting, single stranded 1D-helical nanowires constructed from Cu-Cl and N -methylthiourea (MTCP). The MTCP demonstrates an exceptional response to NH 3 gas (>900% at 100 ppm) and superior selectivity at room temperature compared to current materials. The interaction mechanism between NH 3 and the MTCP sensor is elucidated through a combination of empirical results and computational calculations, leveraging a crystal-determined structure. This reveals the formation of NH 3 -Cu and NH 3 -H 3 C complexes, indicative of a thermodynamically favorable reaction. Additionally, Ag-doped MTCP exhibits higher selectivity and a response over two times greater than the original MTCP, establishing it as a prominent NH 3 detection system at room temperature.

Background: The relationship between mental disorders and oral health is complex, involving behavioral, biological, and psychosocial factors. This review aims to investigate the impact of mental disorders, including autism spectrum disorder (ASD), depression, bipolar disorder, and schizophrenia, on oral health outcomes., Methods: A comprehensive review of existing literature was conducted to analyze the oral health outcomes associated with each mental disorder. The focus was on examining dietary habits, oral hygiene behaviors, physiological changes, and medication side effects that contribute to oral health issues., Results: The findings indicate that individuals with ASD often exhibit unique dietary habits and reduced oral hygiene capabilities due to sensory sensitivities, leading to a higher prevalence of dental caries and periodontal diseases. Depression and bipolar disorder are associated with physiological changes such as reduced saliva production and poor oral hygiene behaviors, increasing the risk of oral health problems. Medications used for these conditions exacerbate issues like xerostomia, further elevating the risk of dental diseases. Schizophrenia poses additional challenges, including cognitive impairments and medication side effects that hinder effective oral care, heightening susceptibility to oral diseases., Conclusions: This review highlights the specific oral health challenges associated with different mental disorders and emphasizes the need for tailored dental care strategies that integrate mental health considerations. The study contributes to the literature by demonstrating the unique oral health impacts of these disorders. However, the findings are limited by the scope of available cross-sectional data and the absence of longitudinal studies. Future research should focus on longitudinal and intervention-based studies to explore causal relationships and develop effective treatments.

Importance: Accurate staging is a fundamental step in treating patients with nasopharyngeal carcinoma (NPC) worldwide; this is crucial not only for prognostication, but also for guiding treatment decisions. The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) system is the global language for clinicians, researchers, and cancer registries. Continual improvement that aligns with contemporary pattern of care is essential., Objective: To improve the prognostic accuracy and clinical applicability of the eighth edition (TNM-8) for NPC., Design, Setting, and Participants: This multicenter study analyzed patients with NPC with detailed tumor features during January 2014 and December 2015 and was reviewed by experienced radiologists. The data analysis was completed in December 2023. The findings were further confirmed with internal and external validation. Statistical analyses and clinical considerations were reviewed by the AJCC/UICC multidisciplinary head and neck panels and attained consensus. The recommendations were evaluated by the AJCC Evidence-Based Medicine Committee before final endorsement as the ninth version (TNM-9)., Main Outcomes and Measures: The primary end point was overall survival. Adjusted hazard ratios of different subgroups were then assessed for confirmation of optimal stage grouping., Results: Of the 4914 patients analyzed, 1264 (25.7%) were female and 3650 (74.3%) were male; the median (SD) age was 48.1 (12.0) years. Advanced radiological extranodal extension (with involvement of adjacent muscles, skin, and/or neurovascular bundles) was identified as an independent adverse factor for all end points: this was added as a criterion for N3. Patients with nonmetastatic disease were regrouped into stages I to III instead of TNM-8 stages I to IVA. Significant hazard discrimination was achieved by grouping T1-2N0-1 as stage I, T3/N2 as stage II, and T4/N3 as stage III. Although the T1-2N0-1 subgroups had comparable 5-year overall survival, subdivisions into IA (T1-T2N0) and IB (T1-T2N1) were recommended due to the distinction in adjusted hazard ratios following adjustment for chemotherapy use. Metastatic disease was exclusively classified as stage IV, and prognostication was further refined by subdivision into IVA (M1a, ≤3 lesions) and IVB (M1b, >3 lesions). TNM-9 demonstrated superiority compared with TNM-8 in major statistical aspects., Conclusion and Relevance: The results of this diagnostic study suggest that the ninth version of TNM staging for NPC, based on robust analyses and a comprehensive review by the AJCC/UICC staging committees, provides an improved staging system for global application and a framework for future incorporation of nonanatomical factors. This will be launched for global application in January 2025.

Objective: Schwannomas are benign, slow-growing tumors originating from Schwann cells in peripheral nerves, commonly affecting the median and ulnar nerves in the forearm and wrist. Surgical excision is the gold standard treatment. This study presents our treatment strategies and outcomes for large-sized ulnar and median nerve schwannomas at the forearm and wrist level., Methods: From 2012 to 2023, we enrolled 15 patients with schwannomas over 2 cm in size in the median or ulnar nerve at the forearm and wrist. The study included 12 patients with median nerve schwannomas (mean age: 61 years) and 3 with ulnar nerve schwannomas (mean age: 68 years), with a mean follow-up of 26.9 months., Results: After surgery, all patients with median nerve schwannomas experienced mild, transient numbness affecting fewer than two digits, resolving within six months without motor deficits. Ulnar nerve schwannoma excision caused mild numbness in two patients, also resolving within six months, but all three developed ulnar claw hand deformity, which persisted but improved at the last follow-up. Despite this, patients were satisfied with the surgery due to relief from severe tingling pain., Conclusions: Schwannomas of the median, ulnar, and other peripheral nerves should be removed by carefully dissecting the connecting nerve fascicles to avoid injury to healthy ones. Sensory deficits may occur but are unlikely to significantly impact quality of life. However, in motor-dominant nerves like the ulnar nerve, there is a risk of significant motor deficits that could affect hand function, though not completely. Therefore, thorough preoperative discussion and consideration of interfascicular nerve grafting are essential., (© 2024. The Author(s).)

Non-optimal temperature is a leading risk factor for global disease burden. Most epidemiological studies assessed only outdoor temperature, with important uncertainties on personal exposure misclassification. The CKB-Air study measured personal, household (kitchen and living room), and outdoor temperatures in the summer (MAY-SEP 2017) and winter (NOV 2017-JAN 2018) in 477 participants in China. After data cleaning, ∼88,000 person-hours of data were recorded across each microenvironment. Using multivariable linear regression (MLR) and random forest (RF) models, we identified key predictors and constructed personal temperature exposure prediction models. We used generalised additive mixed effect models to examine the relationships of personal and outdoor temperatures with heart rate. The 24-hour mean (SD) personal and outdoor temperatures were 29.2 (3.8) °C and 27.6 (6.4) °C in summer, and 12.0 (4.0) °C and 7.5 (4.2) °C in winter, respectively. The temperatures across microenvironments were strongly correlated (Spearman's ρ: 0.86-0.92) in summer. In winter, personal temperature was strongly related to household temperatures (ρ: 0.74-0.79) but poorly related to outdoor temperature (ρ: 0.30). RF algorithm identified household and outdoor temperatures and study date as top predictors of personal temperature exposure for both seasons, and heating-related factors were important in winter. The final MLR and RF models incorporating questionnaire and device data performed satisfactorily in predicting personal exposure in both seasons (R 2 summer : 0.92; R 2 winter : 0.68-0.70). We found consistent U-shaped associations between measured and predicted personal temperature exposures and heart rate (lowest at ∼ 14.5 °C), but a weak positive linear association with outdoor temperature. Personal and outdoor temperatures differ substantially winter, but prediction models incorporating household and outdoor temperatures and questionnaire data performed satisfactorily. Exposure misclassification from using outdoor temperature may produce inappropriate epidemiological findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

This study tested the hypothesis that empagliflozin (EMPA) therapy effectively protected renal and heart functions via downregulating reactive oxygen species (ROS) and activating AMPK signaling in cardiorenal syndrome (CRS) (induced by doxorubicin-5/6 nephrectomy) rats. In vitro result showed that underwent p-Cresol treatment, the H9C2/NRK-52E cell viabilities, were significantly suppressed, whereas cellular levels of ROS and early/late apoptosis of these cells were significantly increased that were significantly reversed by EMPA treatment (all p < 0.001). The protein levels of the cell-stress/oxidative signaling (p-PI3K/p-Akt/p-mTOR/NOXs/p-DRP1) were significantly activated, whereas the mitochondrial biogenesis signaling (p-AMPK/SIRT-1/TFAM/PGC-1α) was significantly repressed in these two cell lines treated by p-Cresol and all of these were significantly reversed by EMPA treatment (all p < 0.001). Male-adult-SD rats were categorized into groups 1 [sham-operated control (SC)]/2 [SC + high protein diet (H PD ) since day 1 after CKD induction]/3 (CRS + H PD )/4 (CRS + H PD +EMPA/20 mg/kg/day) and heart/kidney were harvested by day 60. By day 63, the renal function parameters (creatinine/BUN/proteinuria)/renal artery restrictive index/cellular levels of ROS/inflammation were significantly increased in group 3 than in groups 1/2, whereas heart function exhibited an opposite pattern of ROS among the groups, and all of these parameters were significantly reversed by EMPA treatment (all p < 0.0001). The protein levels of inflammation/ oxidative-stress/cell-stress signalings were highest in group 2, lowest in group 1 and significantly lower in group 4 than in group 2, whereas the AMPK-mitochondrial biogenesis displayed an opposite manner of oxidative-stress among the groups (all p < 0.0001). EMPA treatment effectively protected the heart/kidney against CRS damage via suppressing ROS signaling and upregulating AMPK-mediated mitochondrial biogenesis., (© 2024. The Author(s).)

Objectives: To retrospectively assess the periodontal conditions of teeth adjacent to and contralateral to implants presenting with or without peri-implantitis, following non-surgical periodontal and peri-implant mechanical therapy., Materials and Methods: One hundred and one patients with existing dental implants and chronic periodontitis, who underwent non-surgical periodontal and peri-implant mechanical therapy, were included. The periodontal clinical probing depth (PPD), gingival recession (GR), and bleeding on probing (BOP) were recorded at six sites around the adjacent (Adj-) teeth and the contralateral (CL-) teeth relative to the implant. The potential factors influencing the periodontal conditions of 316 teeth were analyzed by multivariate linear regression models with generalized estimating equation methods and α = .05., Results: The PPD of Adj-teeth was significantly different from that of CL-teeth before and after non-surgical therapy when the implant was diagnosed with peri-implantitis (PI) (p < .05). The PPD of teeth was shown to be affected by neighboring implants diagnosed with peri-implantitis (β = .825 mm, p < .001), teeth adjacent to implants (β = .245 mm, p = .004), a molar tooth type (β = .435 mm, p = .019), and non-surgical therapy (β = -.522 mm, p < .001)., Conclusions: Relatively compromised periodontal conditions at Adj-teeth after non-surgical PI therapy were detected. Therefore, clinicians should be aware that non-surgical therapy may be less successful at teeth adjacent to implants with PI., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Gold standard detection of SARS-CoV-2 by reverse transcription quantitative PCR (RT-qPCR) can achieve ultrasensitive viral detection down to a few RNA copies per sample. Yet, the lengthy detection and labor-intensive protocol limit its effectiveness in community screening. In view of this, a structural switching electrochemical aptamer-based biosensor (E-AB) targeting the SARS-CoV-2 nucleocapsid (N) protein was developed. Four N protein-targeting aptamers were characterized on an electrochemical cell configuration using square wave voltammetry (SWV). The sensor was investigated in an artificial saliva matrix optimizing the aptamer anchoring orientation, SWV interrogation frequency, and target incubation time. Rapid detection of the N protein was achieved within 5 min at a low nanomolar limit of detection (LOD) with high specificity. Specific N protein detection was also achieved in simulated positive saliva samples, demonstrating its feasibility for saliva-based rapid diagnosis. Further research will incorporate novel signal amplification strategies to improve sensitivity for early diagnosis.

Psoriasis is an inflammatory immune-mediated skin disease that affects nearly 2-3 % of the global population. The current study aimed to develop safe and efficient anti-psoriatic nanoformulations from Artemisia monosperma essential oil (EO). EO was extracted using hydrodistillation (HD), microwave-assisted hydrodistillation (MAHD), and head-space solid-phase microextraction (HS-SPME), as well as GC/ MS was used for its analysis. EO nanoemulsion (NE) was prepared using the phase inversion method, while the biodegradable polymeric film (BF) was prepared using the solvent casting technique. A.monosperma EO contains a high percentage of non-oxygenated compounds, being 90.45 (HD), 82.62 (MADH), and 95.17 (HS-SPME). Acenaphthene represents the major aromatic hydrocarbon in HD (39.14 %) and MADH (48.60 %), while sabinene as monoterpene hydrocarbon (44.2 %) is the primary compound in the case of HS-SPME. The anti-psoriatic Effect of NE and BF on the successful delivery of A.monosperma EO was studied using the imiquimod (IMQ)-induced psoriatic model in mice. Five groups (n = 6 mice) were classified into control group, IMQ group, IMQ+standard group, IMQ+NE group, and IMQ+BF group. NE and BF significantly alleviated the psoriatic skin lesions and decreased the psoriasis area severity index, Baker's score, and spleen index. Also, they reduced the expression of Ki67 and attenuated the levels of tumor necrosis factor-alpha, interleukin 6, and interleukin 17. Additionally, NE and NF were able to downregulate the NF-κB and GSK-3β signaling pathways. Despite the healing properties of BF, NE showed a more prominent effect on treating the psoriatic model, which could be referred to as its high skin penetration ability and absorption. These results potentially contribute to documenting experimental and theoretical evidence for the clinical uses of A.monosperma EO nanoformulations for treating psoriasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Facile non-radiative decay of low-lying metal-centered (MC) dd excited states has been well documented to pose a significant obstacle to the development of phosphorescent Ni II complexes due to substantial structural distortions between the dd excited state and the ground state. Herein, we prepared a series of dinuclear Ni 2 II,II complexes by using strong σ-donating carbene-phenyl-carbene (C NHC  C phenyl  C NHC ) pincer ligands, and prepared their dinuclear Pt 2 II,II and Pd 2 II,II analogues. Dinuclear Ni 2 II,II complexes bridged by formamidinate/α-carbolinato ligand exhibit short Ni-Ni distances of 2.947-3.054 Å and singlet metal-metal-to-ligand charge transfer ( 1 MMLCT) transitions at 500-550 nm. Their 1 MMLCT absorption energies are red-shifted relative to the Pt 2 II,II and Pd 2 II,II analogues at ~450 nm and ≤420 nm respectively. One-electron oxidation of these Ni 2 II,II complexes produces valence-trapped dinuclear Ni 2 II,III species, which are characterized by EPR spectroscopy. Upon photoexcitation, these Ni 2 II,II complexes display phosphorescence (τ=2.6-8.6 μs) in the NIR (800-1400 nm) spectral region in 2-MeTHF and in the solid state at 77 K, which is insensitive to π-conjugation of the coordinated [C NHC  C phenyl  C NHC ] ligand. Combined with DFT calculations, the NIR emission is assigned to originate from the 3 dd excited state. Studies have found that the dinuclear Ni 2 II,II complex can sensitize the formation of singlet oxygen and catalyze the oxidation of cyclo-dienes under light irradiation., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Nerve injury can induce aberrant changes in the spine; these changes are due to, or at least partly governed by, transcription factors that contribute to the genesis of neuropathic allodynia. Here, we showed that spinal nerve ligation (SNL, a clinical neuropathic allodynia model) increased the expression of the transcription factor Tbx5 in the injured dorsal horn in male Sprague Dawley rats. In contrast, blocking this upregulation alleviated SNL-induced mechanical allodynia, and there was no apparent effect on locomotor function. Moreover, SNL-induced Tbx5 upregulation promoted the recruitment and interaction of GATA4 and Brd4 by enhancing its binding activity to H3K9Ac, which was enriched at the Trpv1 promotor, leading to an increase in TRPV1 transcription and the development of neuropathic allodynia. In addition, nerve injury-induced expression of Fbxo3, which abates Fbxl2-dependent Tbx5 ubiquitination, promoted the subsequent Tbx5-dependent epigenetic modification of TRPV1 expression during SNL-induced neuropathic allodynia. Collectively, our findings indicated that spinal Tbx5-dependent TRPV1 transcription signaling contributes to the development of neuropathic allodynia via Fbxo3-dependent Fbxl2 ubiquitination and degradation. Thus, we propose a potential medical treatment strategy for neuropathic allodynia by targeting Tbx5., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Introduction: Multidrug-resistant tuberculosis (MDR-TB) remains a challenge in the TB program of Taiwan, where 0.5% of new cases and 2.1% of previously treated cases were resistant to at least rifampin (RIF) and isoniazid (INH). Since >80% of our MDR-TB are new cases, genotyping of MDR Mycobacterium tuberculosis is implemented to facilitate contact investigation, cluster identification, and outbreak delineation., Methods: This is a population-based retrospective cohort study analyzing MDR-TB cases from 2019 to 2022. Whole genome sequencing (WGS) was performed using the Illumina MiSeq and analyzed using the TB Profiler. A single nucleotide polymorphism (SNP) threshold of ≤ 12 and phylogenetic methods were used to identify putative transmission clusters. An outbreak was confirmed using genomic data and epidemiologic links., Results: Of the 297 MDR-TB cases, 246 (82.8%), 45 (15.2%), and 6 (2.0%) were simple MDR, extensively drug-resistant tuberculosis (pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), respectively. The sublineage 2.2 modern Beijing was the predominant (48.8%) MDR-TB strain in Taiwan. Phylogenetic analysis identified 25.3% isolates in 20 clusters, with cluster sizes ranging from 2 to 13 isolates. Nevertheless, only 2 clusters, one household and one community, were confirmed as outbreaks. In this study, we found that males had a higher risk of MDR-TB transmission compared to females, and those infected with the sublineage 2.1-proto-Beijing genotype isolates were at a higher risk of transmission. Furthermore, 161 (54.2%) isolates harbored compensatory mutations in the rpoC and non-rifampicin resistant determinant region (non-RRDR) of the rpoB gene. MDR-TB strains containing rpoB S450L and other compensatory mutations concurrently were significantly associated with clusters, especially the proto-Beijing genotype strains with the compensatory mutation rpoC E750D or the modern Beijing genotype strains with rpoC D485Y/ rpoC E1140D., Discussion: Routine and continuous surveillance using WGS-based analysis is recommended to warn of risks and delineate transmission clusters of MDR-TB. We proposed the use of compensatory mutations as epidemiological markers of M. tuberculosis to interrupt putative MDR-TB transmission., 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 Liu, Xiao and Jou.)

Sacha Inchi ( Plukenetia volubilis ) seeds and oil have been integrated into daily diets. However, scientific reports have raised concerns regarding potential health risks associated with saponins and alkaloids in this seeds. This study employed a combination analysis using proton-NMR, GC-MS, LC-QTOF, and GNPS molecular networking to evaluate the chemical composition of these seeds. In silico toxicology analysis and in vitro cytotoxicity assays were conducted to investigate the potential toxicity effects of Sacha Inchi seeds and their contained metabolites. The results revealed that major components of these seeds are oils (linoleic, linolenic, and oleic acids) and sugars, with minor amounts of phytosterols and trigonelline, a pyridine alkaloid. GNPS analysis suggested the absence of saponins, instead, it identified trigonelline and a few other nitrogen-containing metabolites (amino acids and oligopeptides). In silico toxicology analysis indicated that this sample did not exhibit toxicity. Furthermore, in vitro cytotoxicity screening demonstrated no cytotoxic effects against NIH-3T3 cells, even at 400 μg mL -1 . In general, these findings collectively indicated the absence of saponins, the presence of phytosterols and trigonellin (a pyridine alkaloid), and a low safety risk related to saponin and alkaloid content in the Sacha Inchi seeds., Competing Interests: The authors declare there is no any conflict of interest related to this study., (This journal is © The Royal Society of Chemistry.)

Objective: The study aimed to analyze the outcome of low-dose radioactive iodine (RAI) treatment for hyperthyroidism, disclose whether age and gender influence the outcome and determine the incidence and onset time of hypothyroidism following low-dose RAI., Material and Methods: A total of 158 patients who received doses less than 370 Mbq RAI were enrolled in the study. Treatment outcome and incidence of hypothyroidism were compared between different gender (45 male vs.113 female), age (77 patients ≥45 years old vs. 81 patients <45 years old) and dose (39 patients receiving higher doses RAI vs. 119 receiving lower dose with a cutoff of 222 MBq) groups. Treatment outcomes were categorized into post-treatment hypothyroidism, treatment failure (persistent hyperthyroidism), and euthyroidism. In those becoming hypothyroid, time to develop hypothyroidism was calculated for cumulative incidences over time., Results: Out of 158 patients, 47 (29.7%) developed hypothyroidism, 101 (63.9%) had treatment failure, and 10 (6.3%) remained euthyroid after treatment. Response rates (33.6% vs. 43.5%, p = 0.260) and hypothyroidism incidences (26.9% vs. 38.5%, p = 0.170) did not differ significantly between lower and higher dose groups, neither between lower and higher age groups (p = 0.69 in response rates and p = 0.75 in hypothyroidism incidence). Females exhibited higher response rates (42.5% vs. 20.0%, p = 0.008) and hypothyroidism incidence (46.3% vs. 13.3%, p = 0.004) compared to males. Hypothyroidism onset occurred at a mean of 24.0 ± 29.2 months, and the cumulative incidences over time were 47% and 60% in six and twelve months, respectively., Conclusions: Low-dose RAI has a low response rate for treating hyperthyroidism. Although there may be a lower incidence of hypothyroidism following low-dose RAI compared to high-dose RAI, hypothyroidism may occur early after treatment. Besides, females have higher response rates but more incidence of hypothyroidism. The balance between the risks and benefits of using low-dose RAI should be taken into deliberate consideration., (Copyright © 2024 Sociedad Española de Medicina Nuclear e Imagen Molecular. Published by Elsevier España, S.L.U. All rights reserved.)

This study aims to discuss the identification of the C1 nerve root as an effective surgical approach to successfully locate the shunting point of craniocervical junction spinal dural arteriovenous fistula (CCJ-SDAVF) intraoperatively. This study included all patients with CCJ-SDAVF who underwent surgical treatment using the far-lateral transcondylar approach at a single institution from January 2017 to June 2023. Data on patient demographics, clinical and angiographic characteristics of CCJ-SDAVF, surgical details, and treatment outcomes were collected. Follow-up assessments were conducted for all patients until December 31, 2023. The study included a total of 7 patients, comprising 5 men(71.4%) and 2 women (28.6%), with an average age of 57.6 years. Among them, 4 patients (57.1%) developed diffuse subarachnoid hemorrhage(SAH), while 2 patients (28.6%) experienced progressive cervical myelopathy. The shunting points of all CCJ-SDAVFs, which exhibited engorged veins, were identified next to the C1 root. Complete obliteration of CCJ-SDAVFs was successfully achieved in all patients, as confirmed by postoperative angiography one month later. No recurrent CCJ-SDAVFs were observed two years after the operation. Among the patients, 5 (71.4%) experienced good functional recovery, as indicated by an mRS score ranging from 0 to 1, while the remaining 2 patients (28.6%) showed incomplete functional recovery. The surgical interruption of CCJ-SDAVFs is the preferred treatment option, given its high obliteration rate and favorable functional recovery outcomes. We advocate the identification of C1 spinal nerve root as a crucial surgical step to identify the shunting points of CCJ- SDAVFs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The interleukin (IL)-1 family is a major proinflammatory cytokine family, ranging from the well-studied IL-1s to the most recently discovered IL-33. As a new focus, IL-33 has attracted extensive research for its crucial immunoregulatory roles, leading to the development of notable monoclonal antibodies as clinical candidates. Efforts to develop small molecules disrupting IL-33/ST2 interaction remain highly desired but encounter challenges due to the shallow and featureless interfaces. The information from relative cytokines has shown that traditional binding site identification methods still struggle in mapping cryptic sites, necessitating dynamic approaches to uncover druggable pockets on IL-33. Here, we employed mixed-solvent molecular dynamics (MixMD) simulations with diverse-property probes to map the hotspots of IL-33 and identify potential binding sites. The protocol was first validated using the known binding sites of two IL-1 family members and then applied to the structure of IL-33. Our simulations revealed several binding sites and proposed side-chain rearrangements essential for the binding of a known inhibitor, aligning well with experimental NMR findings. Further microsecond-time scale simulations of this IL-33-protein complex unveiled distinct binding modes with varying occurrences. These results could facilitate future efforts in developing ligands to target challenging flexible pockets of IL-33 and IL-1 family cytokines in general.

Background: Controlling saturated fat and cholesterol intake is important for the prevention of cardiovascular diseases. Although the use of mobile diet-tracking apps has been increasing, the reliability of nutrition apps in tracking saturated fats and cholesterol across different nations remains underexplored., Objective: This study aimed to examine the reliability and consistency of nutrition apps focusing on saturated fat and cholesterol intake across different national contexts. The study focused on 3 key concerns: data omission, inconsistency (variability) of saturated fat and cholesterol values within an app, and the reliability of commercial apps across different national contexts., Methods: Nutrient data from 4 consumer-grade apps (COFIT, MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!) and an academic app (Formosa FoodApp) were compared against 2 national reference databases (US Department of Agriculture [USDA]-Food and Nutrient Database for Dietary Studies [FNDDS] and Taiwan Food Composition Database [FCD]). Percentages of missing nutrients were recorded, and coefficients of variation were used to compute data inconsistencies. One-way ANOVAs were used to examine differences among apps, and paired 2-tailed t tests were used to compare the apps to national reference data. The reliability across different national contexts was investigated by comparing the Chinese and English versions of MyFitnessPal with the USDA-FNDDS and Taiwan FCD., Results: Across the 5 apps, 836 food codes from 42 items were analyzed. Four apps, including COFIT, MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!, significantly underestimated saturated fats, with errors ranging from -13.8% to -40.3% (all P<.05). All apps underestimated cholesterol, with errors ranging from -26.3% to -60.3% (all P<.05). COFIT omitted 47% of saturated fat data, and MyFitnessPal-Chinese missed 62% of cholesterol data. The coefficients of variation of beef, chicken, and seafood ranged from 78% to 145%, from 74% to 112%, and from 97% to 124% across MyFitnessPal-Chinese, MyFitnessPal-English, and LoseIt!, respectively, indicating a high variability in saturated fats across different food groups. Similarly, cholesterol variability was consistently high in dairy (71%-118%) and prepackaged foods (84%-118%) across all selected apps. When examining the reliability of MyFitnessPal across different national contexts, errors in MyFitnessPal were consistent across different national FCDs (USDA-FNDSS and Taiwan FCD). Regardless of the FCDs used as a reference, these errors persisted to be statistically significant, indicating that the app's core database is the source of the problems rather than just mismatches or variances in external FCDs., Conclusions: The findings reveal substantial inaccuracies and inconsistencies in diet-tracking apps' reporting of saturated fats and cholesterol. These issues raise concerns for the effectiveness of using consumer-grade nutrition apps in cardiovascular disease prevention across different national contexts and within the apps themselves., (© Dang Khanh Ngan Ho, Wan-Chun Chiu, Jing-Wen Kao, Hsiang-Tung Tseng, Cheng-Yu Lin, Pin-Hsiang Huang, Yu-Ren Fang, Kuei-Hung Chen, Ting-Ying Su, Chia-Hui Yang, Chih-Yuan Yao, Hsiu-Yueh Su, Pin-Hui Wei, Jung-Su Chang. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org).)

Objective: Mitotically active cellular fibroma (MACF) of the ovary, characterized by relatively high mitotic activity without severe atypia, was first described in the WHO classification in 2014. However, due to its rarity, the clinicopathological characteristics of ovarian MACF have not been established. This study was performed to describe the clinical, radiological, and pathological features of MACF by analyzing 11 cases of ovarian MACF., Materials and Methods: Between 2015 and 2022, 11 patients with ovarian MACFs underwent surgical treatment at our institution. Clinicopathologic data of the patients were retrospectively reviewed from their medical records., Results: Median patient age was 53.7 years (range 21-77 years), and median tumor diameter was 7.8 cm (range 4.3-14.0 cm). Preoperative CA125 was elevated in 4 cases. Four of the eleven patients had abdominal pain, and two presented with vulvar pain or a palpable abdominal mass, respectively. Preoperative radiological impressions included fibroma, fibrothecoma, stromal tumor, and cystadenocarcinoma. A laparoscopic approach was adopted in 7 cases (64%). Intraoperative frozen section was performed in 5 patients, and all demonstrated the presence of a benign, fibromatous stromal tumor. Three patients underwent fertility-sparing surgery, including laparoscopic ovarian cystectomy and unilateral salpingo-oophorectomy. Median follow-up was 37.7 months (range 2-84 months), and no patient experienced disease relapse or died of their disease., Conclusion: This study shows that ovarian MACF has a benign clinical course. Fertility-sparing surgery provides a safe therapeutic option for MACF, which can be managed safely by laparoscopy. Imaging findings and final pathological diagnosis were not well matched. Intraoperative frozen section is important for determining surgical extent in mitotically active cellular fibroma of the ovary., Competing Interests: Conflicts of interest The authors declare no conflicts of interest related to this manuscript., (Copyright © 2024. Published by Elsevier B.V.)

The mortality and hospitalization rate by COVID-19 dropped significantly currently, but its seasonal outbreaks make antiviral treatment still vital. The mortality and hospitazation rate by COVID-19 dropped significantly currently, but its seasonal ourbreaks make antiviral treatment still vital. In our study, syrian golden hamsters were treated with molnupiravir and interferons (IFNs) after SARS-CoV-2 infection. Their weight changes, pathological changes, virus replication and inflammation levels were evaluated. In the IFNs single treatment, only IFN-α group reduced viral load (p < 0.05) and virus titer in hamster lungs. The TNF-α expression decreased significantly in both IFNs treatment at 2dpi. Histological and immunofluorescence results showed lung damage in the IFNs groups were milder at 4dpi. In the molnupiravir/IFN-α combination treatment, weight loss and virus replication in lung were significantly decreased in the mono-molnupiravir group and combination group (p < 0.05), the expression of IL-6, TNF-α, IL-1β and MIP-1α also decreased significantly (p < 0.05), but the combination treatment was not more effective than the mono-molnupiravir treatment. Histological and immunofluorescence results showed the lung damage and inflammation in mono-molnupiravir and combination groups were milder. In summary, IFNs treatment had anti-inflammatory effect against SARS-CoV-2, only IFN-α showed a weak antiviral effect. Molnupiravir/IFN-α combination treatment was effective against SARS-CoV-2 but was not superior to mono-molnupiravir treatment. IFN-α could be considered for immunocompromised patients to stimulate and activate early immune responses., (© 2024 Wiley Periodicals LLC.)

Nociceptors are key sensory receptors that transmit warning signals to the central nervous system in response to painful stimuli. This fundamental process is emulated in an electronic device by developing a novel artificial nociceptor with an ultrathin, nonstoichiometric gallium oxide (GaO x )-silicon oxide heterostructure. A large-area 2D-GaO x film is printed on a substrate through liquid metal printing to facilitate the production of conductive filaments. This nociceptive structure exhibits a unique short-term temporal response following stimulation, enabling a facile demonstration of threshold-switching physics. The developed heterointerface 2D-GaO x film enables the fabrication of fast-switching, low-energy, and compliance-free 2D-GaO x nociceptors, as confirmed through experiments. The accumulation and extrusion of Ag in the oxide matrix are significant for inducing plastic changes in artificial biological sensors. High-resolution transmission electron microscopy and electron energy loss spectroscopy demonstrate that Ag clusters in the material dispersed under electrical bias and regrouped spontaneously when the bias is removed owing to interfacial energy minimization. Moreover, 2D nociceptors are stable; thus, heterointerface engineering can enable effective control of charge transfer in 2D heterostructural devices. Furthermore, the diffusive 2D-GaO x device and its Ag dynamics enable the direct emulation of biological nociceptors, marking an advancement in the hardware implementation of artificial human sensory systems., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Graph convolutional networks (GCNs) have emerged as a powerful tool for action recognition, leveraging skeletal graphs to encapsulate human motion. Despite their efficacy, a significant challenge remains the dependency on huge labeled datasets. Acquiring such datasets is often prohibitive, and the frequent occurrence of incomplete skeleton data, typified by absent joints and frames, complicates the testing phase. To tackle these issues, we present graph representation alignment (GRA), a novel approach with two main contributions: 1) a self-training (ST) paradigm that substantially reduces the need for labeled data by generating high-quality pseudo-labels, ensuring model stability even with minimal labeled inputs and 2) a representation alignment (RA) technique that utilizes consistency regularization to effectively reduce the impact of missing data components. Our extensive evaluations on the NTU RGB+D and Northwestern-UCLA (N-UCLA) benchmarks demonstrate that GRA not only improves GCN performance in data-constrained environments but also retains impressive performance in the face of data incompleteness.

Objectives: The long-term risk of developing glaucoma after vitrectomy remains uncertain. This retrospective population-based cohort study aimed to explore this risk following vitrectomy for macular pucker or hole., Methods: Utilizing Taiwan's National Health Insurance Research Database (NHIRD), we included patients who were older than 18 years and had undergone vitrectomy surgery between 2011 and 2019. Exclusions were made for patients with prior diagnoses of glaucoma, congenital or secondary glaucoma, as well as those who had received previous vitreoretinal treatments or had undergone multiple vitrectomies., Results: After an average follow-up period of 51 and 53 months respectively for the vitrectomized and non-vitrectomized group, our results showed a relative risk of 1.71 for glaucoma development in the vitrectomized group. Higher adjusted hazard ratios were also observed for open-angle glaucoma and normal tension glaucoma. Increased risks were associated with male sex, obstructive sleep apnoea, and migraine. In the subgroup analysis, phakic eyes at baseline and those who had undergone cataract surgery post-vitrectomy were associated with a lower risk of glaucoma development during follow-up. Among all glaucoma events, pseudophakic status at baseline had the shortest interval to glaucoma development following vitrectomy., Conclusions: These findings underscore the potential relationship between vitrectomy and glaucoma onset, emphasizing the need for vigilant monitoring and early detection of glaucoma in post-vitrectomy patients., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Satellite cells are skeletal muscle stem cells that contribute to postnatal muscle growth, and they endow skeletal muscle with the ability to regenerate after a severe injury. Here we discover that this myogenic potential of satellite cells requires a protein called tripartite motif-containing 28 (TRIM28). Interestingly, different from the role reported in a previous study based on C2C12 myoblasts, multiple lines of both in vitro and in vivo evidence reveal that the myogenic function of TRIM28 is not dependent on changes in the phosphorylation of its serine 473 residue. Moreover, the functions of TRIM28 are not mediated through the regulation of satellite cell proliferation or differentiation. Instead, our findings indicate that TRIM28 regulates the ability of satellite cells to progress through the process of fusion. Specifically, we discover that TRIM28 controls the expression of a fusogenic protein called myomixer and concomitant fusion pore formation. Collectively, the outcomes of this study expose the framework of a novel regulatory pathway that is essential for myogenesis., (© 2024. The Author(s).)

Proper topographically organized neural connections between the thalamus and the cerebral cortex are mandatory for thalamus function. Thalamocortical (TC) fiber growth begins during the embryonic period and completes by the third trimester of gestation, so that human neonates at birth have a thalamus with a near-facsimile of adult functional parcellation. Whether congenital neocortical anomaly (e.g., lissencephaly) affects TC connection in humans is unknown. Here, via diffusion MRI fiber-tractography analysis of long-term formalin-fixed postmortem fetal brain diagnosed as lissencephaly in comparison with an age-matched normal one, we found similar topological patterns of thalamic subregions and of internal capsule parcellated by TC fibers. However, lissencephaly fetal brain showed white matter structural changes, including fewer/less organized TC fibers and optic radiations, and much less cortical plate invasion by TC fibers - particularly around the shallow central sulcus. Diffusion MRI fiber tractography of normal fetal brains at 15, 23, and 26 gestational weeks (GW) revealed dynamic volumetric change of each parcellated thalamic subregion, suggesting coupled developmental progress of the thalamus with the corresponding cortex. Moreover, from GW23 and GW26 normal fetal brains, TC endings in the cortical plate could be delineated to reflect cumulative progressive TC invasion of cortical plate. By contrast, lissencephaly brain showed a dramatic decrease in TC invasion of the cortical plate. Our study thus shows the feasibility of diffusion MRI fiber tractography in postmortem long-term formalin-fixed fetal brains to disclose the developmental progress of TC tracts coordinating with thalamic and neocortical growth both in normal and lissencephaly fetal brains at mid-gestational stage., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The Chinese Haemophilia Individualized Prophylaxis Study (CHIPS), which was launched in 2016, reported a significant reduction in haemarthrosis over a one-year study. However, its long-term efficacy requires verification. This paper summarizes the clinical outcomes of 18 severe haemophilia A (SHA) patients who completed one year on the CHIPS and 3 more years of follow-up., Methods: Clinical follow-up was based on the CHIPS protocol (from July 2018 to July 2021). Escalation was based on index joint bleeding, and serial ultrasound (greyscale and colour Doppler) examinations of the index joints (both sides of the ankles, knees and elbows) were conducted every 6 months via a scoring system., Results: A total of 18 SHA patients completed the 3-year study. Fifteen patients dropped out due to the financial crisis during the COVID-19 pandemic in China. The median age was 5.4 (range 4.3-6.9) years. A significant reduction in haemarthrosis was achieved, with mean annual bleeding rates reduced from 18.9 ± 2.8 to 1.7 ± 0.4 (p < 0.001), annual joint bleeding rates from 3.1 ± 0.7 to1.2 ± 0.3 (p < 0.028). 5 out of 8 target joint resolved. Sixteen doses were escalated. At study exit, the heterogeneous treatment outcomes of the SHA boys were 5 at step 4 (20-25 lU/kg, every other day), 10 at step 3 (15-20 IU/kg, 3×/week), 2 at step 2 (10-15 lU/kg, 3×/week) and 1 at step 1 (10-15 lU/kg, 2×/week). The mean FVIII consumption was 2964 IU/kg/year, with savings. The quality of life improved, with Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT, Chinese Version 2.0) scores ranging from 68.8 to 78.8. There was no change in the ultrasound score., Conclusion: Our follow-up data on the 18 SHA boys after completing one year on the CHIPS verify the long-term efficacy of the CHIPS for haemarthrosis reduction, joint health preservation, improvement in the quality of life of the boys and cost savings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Esophageal squamous cell carcinoma (ESCC) is a particularly aggressive form of cancer with high mortality. In the present study, a novel 8‑hydroxyquinoline derivative (91b1) was investigated for its anticancer activities in ESCC along with its associated mechanisms. The in vitro cytotoxic effect of 91b1 were evaluated across five ESCC cell lines using MTS assay, with cisplatin serving as a comparative standard. Changes in gene expression profile were identified by cDNA microarray and further validated by qualitative PCR and immunostaining. Additionally, protein levels of the most notably downregulated target in archival ESCC samples were also studied. 91b1 demonstrated comparable anticancer effect with cisplatin. Notably, chemokine ligand 5 (Ccl5) was identified as the most substantially downregulated gene, with its suppression at both mRNA and protein expression in ESCC cells, exhibiting a dose‑dependent manner. The recombinant human protein of CCL5 enhanced the invasion of ESCC cells using the Transwell assay. The upregulation of CCL5 protein was also detected in 50% of ESCC cell lines. CCL5 was also overexpressed in 76.9% of ESCC specimens. The overall results indicated that 91b1 could effectively induce anticancer effect on ESCC cells through downregulating CCL5 expression with suppression of tumor invasion. Overall, these findings suggested that 91b1 effectively inhibited ESCC cell proliferation and tumor invasion by downregulating CCL5 expression, highlighting its potential as a therapeutic agent for ESCC treatment.

Context: Pyrus calleryana Decne (Rosaceae), renowned for its therapeutic properties, is known to moisturize the lungs (removing dryness; relieving cough), clear heat (acting as an antipyretic; febrifuge) and aid in detoxification (relieving pyogenic inflammation; eliminating toxins). However, scientific evidence supporting its efficacy in wound healing is lacking., Objective: This study investigated P. calleryana samples collected over a year to explore metabolite variations and their impact on skin wound-healing activities., Materials and Methods: P. calleryana (PC) twigs and leaves were collected from the Matsu Islands, Taiwan, spanning 2018-2020. Extracts were prepared using 95% ethanol or water, and we assessed the chemical composition, total phenolic/triterpenoid contents and antioxidant properties. Metabolites were analysed via LC-MS/MS and molecular networking. Wound healing potential was evaluated on WS-1 cells through MTT and migration assays, and gene expression analyses, with tests including control (DMSO), compounds 1 (3'-hydroxylbenzyl-4-hydroxybenzoate-4'- O -β-glucopyranoside) and 2 (vanilloylcalleryanin) (100 µM), and a positive control (ascorbic acid, 100 µM) for 24 h., Results: Significant variations in extract compositions were observed based on the solvent used, with distinct metabolomic profiles in extracts collected during different months. Notably, compounds 1 and 2 showed no cytotoxic effects on human dermal fibroblast cells and significantly accelerated wound closure at 100 μM. A gene expression analysis indicated upregulation of wound healing-associated genes, including MMP-1 (matrix metalloproteinase-1) and COL1A1 (collagen, type 1, alpha 1)., Conclusions: This study reports the first evidence of PC compounds aiding wound healing. Utilizing Global Natural Products Social Molecular Networking (GNPS) and principal component analysis (PCA) approaches, we unveiled metabolomic profiles, suggesting the potential to expedite wound-healing.

Purpose: To investigate the potential of virtual contrast-enhanced magnetic resonance imaging (VCE-MRI) for gross-tumor-volume (GTV) delineation of nasopharyngeal carcinoma (NPC) using multi-institutional data., Methods and Materials: This study retrospectively retrieved T1-weighted (T1w), T2-weighted (T2w) MRI, gadolinium-based contrast-enhanced MRI (CE-MRI), and planning computed tomography (CT) of 348 biopsy-proven NPC patients from 3 oncology centers. A multimodality-guided synergistic neural network (MMgSN-Net) was trained using 288 patients to leverage complementary features in T1w and T2w MRI for VCE-MRI synthesis, which was independently evaluated using 60 patients. Three board-certified radiation oncologists and 2 medical physicists participated in clinical evaluations in 3 aspects: image quality assessment of the synthetic VCE-MRI, VCE-MRI in assisting target volume delineation, and effectiveness of VCE-MRI-based contours in treatment planning. The image quality assessment includes distinguishability between VCE-MRI and CE-MRI, clarity of tumor-to-normal tissue interface, and veracity of contrast enhancement in tumor invasion risk areas. Primary tumor delineation and treatment planning were manually performed by radiation oncologists and medical physicists, respectively., Results: The mean accuracy to distinguish VCE-MRI from CE-MRI was 31.67%; no significant difference was observed in the clarity of tumor-to-normal tissue interface between VCE-MRI and CE-MRI; for the veracity of contrast enhancement in tumor invasion risk areas, an accuracy of 85.8% was obtained. The image quality assessment results suggest that the image quality of VCE-MRI is highly similar to real CE-MRI. The mean dosimetric difference of planning target volumes was less than 1 Gy., Conclusions: The VCE-MRI is highly promising to replace the use of gadolinium-based CE-MRI in tumor delineation of NPC patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Understanding factors affecting the infectiousness of influenza cases is crucial for disease prevention and control. Viral shedding is expected to correlate with infectiousness of cases, but it is strongly associated with age and the presence of symptoms., Methods: To elucidate this complex interplay, we analyze with an individual-based household transmission model a detailed household transmission study of influenza with 442 households and 1710 individuals from 2008 to 2017 in Hong Kong, to characterize the household transmission dynamics and identify factors affecting transmissions., Results: We estimate that age, fever symptoms and viral load were all associated with higher infectiousness. However, by model comparison, the best model includes age and fever as factors affecting individual infectiousness, and estimates that pre-school and school-age children were 317% (95% credible interval (CrI): 103%, 1042%) and 161% (95% CrI: 33%, 601%) more infectious than adults respectively, and patients having fever had 146% (95% CrI: 37%, 420%) higher infectiousness. Adding heterogeneity on individual infectiousness of cases does not improve the model fit, suggesting these factors could explain the difference in individual infectiousness., Conclusions: Our study clarifies the contribution of age, symptoms and viral shedding to individual infectiousness of influenza cases in households., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)