bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatially Resolved Fibre‐Optic Probe for Cervical Precancer Detection Using Fluorescence Spectroscopy and PCA‐ANN‐Based Classification Algorithm: An In Vitro Study
Authors: Shukla Shivam , Deo Bhaswati Singha , Nemichand  , Singh Pankaj , Pandey Prabodh Kumar , Pradhan Asima 
Published: October 2024

ABSTRACTCervical cancer can be detected at an early stage through the changes occurring in biochemical and morphological properties of epithelium layer. Fluorescence spectroscopy has the ability to identify these subtle changes non‐invasively and in real time with good accuracy in comparison with conventional techniques. In this paper, we report the usage of a custom designed spatially resolved fibre‐optic probe (SRFOP), which consists of 77 fibres in two concentric rings, for the detection of cervical cancer using fluorescence spectroscopy technique. The aim of this study is to classify different grades of cervical precancer on the basis of their fluorescence spectra followed by a robust classification algorithm. Fluorescence spectra of 28 cervical tissue samples of different categories have been recorded using six detector fibres of FOP at different spatial locations with the source fibre (SF). A 405 nm laser diode source has been utilised to excite the samples and a USB 4000 Ocean Optics spectrometer to collect the output spectra in the wavelength range 400–700 nm. Principal component analysis (PCA) was applied to the collected spectra to reduce the dimensionality of the data while preserving the most significant features for classification. The first 10 principal components, which captured the majority of the variance in the spectra, were selected as input features for the classification model. Classification was then performed using an artificial neural network (ANN) with a specific architecture, including an input layer, hidden layers, and a softmax activation function in the output layer. Experimental and classification results both demonstrate that proximal fibres (PFs) perform better than distal fibres (DFs) in capturing the discriminatory features present in the epithelium layer of cervical tissue samples as PF collect most of the signal from the epithelium layer. The combined approach of spatially resolved fluorescence spectroscopy and PCA‐ANN classification techniques is able to discriminate different grades of cervical precancer and normal with an average sensitivity, specificity and accuracy of 93.33%, 96.67% and 95.57%, respectively.
Role of Sodium‐Dependent Vitamin C Transporter‐2 and Ascorbate in Regulating the Hypoxic Pathway in Cultured Glioblastoma Cells
Authors: Burgess Eleanor R. , Praditi Citra , Phillips Elisabeth , Vissers Margreet C. M. , Robinson Bridget A. , Dachs Gabi U. , Wiggins George A. R. 
Published: October 2024

ABSTRACTThe most common and aggressive brain cancer, glioblastoma, is characterized by hypoxia and poor survival. The pro‐tumour transcription factor, hypoxia‐inducible factor (HIF), is regulated via HIF‐hydroxylases that require ascorbate as cofactor. Decreased HIF‐hydroxylase activity triggers the hypoxic pathway driving cancer progression. Tissue ascorbate accumulates via the sodium‐dependent vitamin C transporter‐2 (SVCT2). We hypothesize that glioblastoma cells rely on SVCT2 for ascorbate accumulation, and that knockout of this transporter would disrupt the regulation of the hypoxic pathway by ascorbate. Ascorbate uptake was measured in glioblastoma cell lines (U87MG, U251MG, T98G) by high‐performance liquid chromatography. CRISPR/Cas9 was used to knockout SVCT2. Cells were treated with cobalt chloride, desferrioxamine or 5% oxygen, with/without ascorbate, and key hypoxic pathway proteins were measured using Western blot analysis. Ascorbate uptake was cell line dependent, ranging from 1.7 to 11.0 nmol/106 cells. SVCT2‐knockout cells accumulated 90%–95% less intracellular ascorbate than parental cells. The hypoxic pathway was induced by all three stimuli, and ascorbate reduced this induction. In the SVCT2‐knockout cells, ascorbate had limited effect on the hypoxic pathway. This study verifies that intracellular ascorbate is required to suppress the hypoxic pathway. As patient survival is related to an activated hypoxic pathway, increasing intra‐tumoral ascorbate may be of clinical interest.
Prognostic Nutritional Index is Related to All‐Cause Mortality in Patients With Stage IV Colorectal Cancer Treated With Capecitabine: Single‐Center 24‐Month Observational Study in Vietnam
Authors: Nguyen Quang Hung , Nguyen Duc Luan , Hoang Van Hieu , Vu Anh Hai , Nguyen Trung Kien , Le Viet Thang 
Published: October 2024

ABSTRACTAimTo determine the mortality rate and the predictive value of the prognostic nutritional index (PNI) for all‐cause mortality during the 24 months in patients with stage IV colorectal cancer treated with capecitabine.MethodsWe conducted a study on 87 stage IV colorectal cancer patients treated with capecitabine. Before the day of treatment, all patients were measured CEA and CRP‐hs levels and calculated neutrophil/lympho ratio (NLR) and PNI. Patients were monitored and collected drug side effects and mortality for 24 months.ResultsThe mortality rate of study subjects was 60.9%. CRP‐hs, NLR, and PNI were independent factors associated with 24‐month mortality in patients with stage IV colorectal cancer (p < 0.05 to p < 0.01). At a cut‐off value of 38.51, PNI was a predictor for mortality, with the area under the curve (AUC) of 0.88 and p < 0.001.ConclusionsPNI was a good predictor of all‐cause mortality in patients with stage IV colorectal cancer treated with capecitabine for 24 months.
A combination of major histocompatibility complex (MHC) I overexpression and type I interferon induce mitochondrial dysfunction in human skeletal myoblasts
Authors: Thoma Anastasia , Alomosh Razan , Bond Holly L. , Akter‐Miah Tania , Al‐Shanti Nasser , Degens Hans , Pekovic‐Vaughan Vanja , Lightfoot Adam P. 
Published: October 2024

AbstractThe overexpression of major histocompatibility complex (MHC) I on the surface of muscle fibers is a characteristic hallmark of the idiopathic inflammatory myopathies (IIMs), collectively termed myositis. Alongside MHC‐I overexpression, subtypes of myositis, display a distinct type I interferon (IFN) signature. This study examined the combinational effects of elevated MHC‐I and type I IFNs (IFNα/β) on mitochondrial function, as mitochondrial dysfunction is often seen in IIMs. Human skeletal muscle myoblasts were transfected with an MHC‐I isoform using the mammalian HLA‐A2/Kb vector. Mitochondrial respiration, mitochondrial membrane potential, and reactive oxygen/nitrogen species generation were assessed with or without IFNα and IFNβ. We show that MHC‐I overexpression in human skeletal muscle myoblasts led to decreased basal glycolysis and mitochondrial respiration, cellular spare respiratory capacity, adenosine triphosphate‐linked respiration, and an increased proton leak, which were all exaggerated by type I IFNs. Mitochondrial membrane depolarization was induced by MHC‐I overexpression both in absence and presence of type I IFNs. Human myoblasts overexpressing MHC‐I showed elevated nitric oxide generation that was abolished when combined with IFN. MHC‐I on its own did not result in an increased reactive oxygen species (ROS) production, but IFN on their own, or combined with MHC‐I overexpression did induce elevated ROS generation. Surprisingly, we observed no gross changes in mitochondrial reticular structure or markers of mitochondrial dynamics. We present new evidence that MHC‐I overexpression and type I IFNs aggravate the effects each has on mitochondrial function in human skeletal muscle cells, providing novel insights into their mechanisms of action and suggesting important implications in the further study of myositis pathogenesis.
Inflammation Decreases Ciclosporin Metabolism in Allogeneic Hematopoietic Stem Cell Transplantation Recipients
Authors: Malnoë David , Bories Mathilde , Pierre‐Jean Morgane , Marchand Tony , Le Corre Pascal 
Published: October 2024

AbstractGraft‐versus‐host disease (GVHd) remains a significant challenge following allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of GVHd relies mainly on the use of calcineurin inhibitors, notably ciclosporin that exhibits complex pharmacokinetics influenced by many factors including drug‐drug interactions (DDIs). Due to the downregulation of drug metabolizing enzymes and transporters, it has been postulated that inflammation may be a contributing factor to the variability observed in ciclosporin pharmacokinetics.This study aimed to assess the impact of inflammation, as indicated by C‐reactive protein (CRP) levels, on the metabolism of ciclosporin in adult allogeneic HSCT recipients. A retrospective observational study was conducted at Rennes University Hospital involving 71 adult HSCT patients. The relationship between the intensity of inflammation (no‐to‐mild, moderate, and severe), and the metabolism of ciclosporin (estimated by the concentration/dose ratio) was assessed. Severe inflammation significantly decreased the metabolism of ciclosporin, as evidenced by higher concentration/dose ratios. Thanks to the daily dose adjustment, inflammation did not influence the blood levels of ciclosporin. Interestingly, DDIs did not emerge as a significant covariate in influencing ciclosporin metabolism. This is likely because the CYP3A4 inhibitory potential of interacting drugs may be masked in HSCT patients where metabolism is already upstream downregulated by inflammation.The study highlights the intricate relationship between inflammation and ciclosporin pharmacokinetics in HSCT patients. This underscores the necessity for therapeutic monitoring and the potential adjustment of dosage strategies based on the inflammatory status. These insights could contribute to the development of more personalized, optimized, and effective management strategies for HSCT recipients.
A phase III, open‐label clinical trial evaluating pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease previously treated with other enzyme replacement therapies
Authors: Holida Myrl , Linhart Aleš , Pisani Antonio , Longo Nicola , Eyskens François , Goker‐Alpan Ozlem , Wallace Eric , Deegan Patrick , Tøndel Camilla , Feldt‐Rasmussen Ulla , Hughes Derralynn , Sakov Anat , Rocco Rossana , Almon Einat Brill , Alon Sari , Chertkoff Raul , Warnock David G. , Waldek Stephen , Wilcox William R. , Bernat John A. 
Published: October 2024

AbstractPegunigalsidase alfa, a PEGylated α‐galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half‐life than other ERTs administered intravenously every 2 weeks (E2W). BRIGHT (NCT03180840) was a phase III, open‐label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks. Primary objective assessed safety, including number of treatment‐emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4‐week dosing interval. Thirty‐three of 182 TEAEs (in 9 patients) were considered treatment‐related; all were mild/moderate. No patients developed de novo anti‐drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter‐quartile range) eGFR change from baseline over 52 weeks was −1.9 (−5.9; 1.8) mL/min/1.73 m2 (n = 28; males [n = 22]: –2.4 [−5.2; 3.2]; females [n = 6]: −0.7 [−9.2; 2.0]). Overall, median eGFR slope was –1.9 (−8.3; 1.9) mL/min/1.73 m2/year (ADA‐negative [n = 20]: −1.2 [−6.4; 2.6]; ADA‐positive [n = 9]: −8.4 [−11.6; –1.0]). Lyso‐Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA‐positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W.Take‐home messageTreatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease.
Extended long‐term efficacy and safety of velmanase alfa treatment up to 12 years in patients with alpha‐mannosidosis
Authors: Guffon Nathalie , Borgwardt Line , Tylki‐Szymańska Anna , Ballabeni Andrea , Donà Francesca , Joseph Amer , Nienhuis Henriët , Maugeri Caterina , Lund Allan 
Published: October 2024

AbstractEnzyme replacement therapy (ERT) using velmanase alfa previously showed promising efficacy and safety outcomes for up to 4 years of therapy in patients with alpha‐mannosidosis. This pooled analysis from two multicenter, open‐label phase IIIb extension trials rhLAMAN‐07 (N = 13; NCT01908712) and rhLAMAN‐09 (N = 8; NCT01908725) evaluated the long‐term effects of velmanase alfa. Sixteen patients who previously completed phase I–III rhLAMAN‐02/‐03/‐04/‐05/‐08 trials and five ERT‐naïve patients were enrolled. Patients received 1 mg/kg velmanase alfa once weekly. Endpoints included changes from treatment baseline (before initial dose of velmanase alfa in any trial) in serum oligosaccharides, 6‐minute walk test (6MWT), 3‐minute stair climb test (3MSCT), pulmonary function (forced vital capacity [FVC], % predicted), serum immunoglobulin G (IgG) levels, and adverse events. The overall cohort comprised 21 patients, divided by age at treatment baseline into pediatric (n = 14) and adult subgroups (n = 7). Distance walked according to 6MWT increased or stabilized in pediatric patients, while in adults either stabilization or slight decline was observed. Similarly, pediatric patients performed better in the 3MSCT. Changes in FVC, % predicted, were comparable in both subgroups up to ~6 years of observation, diverging thereafter. Overall, sustained serum oligosaccharide clearance and serum IgG level increase was observed upon treatment initiation and persisted until last common observation. Velmanase alfa treatment was generally well tolerated, with the majority of reported adverse events being of mild‐to‐moderate intensity. With follow‐up of up to 12 years, long‐term efficacy and safety outcomes indicate continued benefits of velmanase alfa in patients with alpha‐mannosidosis.
A Spatial Interpolation Method for Meteorological Data Based on a Hybrid Kriging and Machine Learning Approach
Authors: Huang Julong , Lu Chuhan , Huang Dingan , Qin Yujing , Xin Fei , Sheng Hao 
Published: October 2024

ABSTRACTConventional spatial interpolation methods for meteorological data are usually based on linear interpolation. However, with the improvements in the temporal and spatial resolution of observational data, local neighbouring stations are susceptible to the influence of underlying surface changes and high terrain gradients. Moreover, for interpolation at a single time point, the inability to extract continuous change information effectively from adjacent times limits the interpolation performance. In this paper, an improved hybrid deep learning‐kriging method is proposed that combines a graph neural networks (GNNs) prediction model with the kriging interpolation algorithm. The GNNs considers dynamic changes over time and combines spatial and temporal information to estimate (interpolate) meteorological data at target weather stations using reanalysis data as input. The experimental results show that the hybrid method exhibits good performance in interpolating station data in complex terrain areas and under uneven surface conditions. The interpolation effectiveness of this method is markedly improved compared to that of traditional kriging methods. Moreover, when applied to station‐to‐grid interpolation, the hybrid method still provides better interpolation results than those of kriging methods. Therefore, this research provides a new method and perspective for meteorological data interpolation.
Systemic immune‐inflammation states in US adults with seropositivity to infectious pathogens: A nutrient‐wide association study
Authors: Xie He , Halimulati Mairepaiti , Dou Yuqi , Zhang Hanyue , Jiang Xiaowen , Peng Lei 
Published: October 2024

AbstractBackgroundLimited understanding exists regarding the association between daily total dietary nutrient intakes and immune‐inflammation states in US adults exposed to various pathogens. This study sought to examine the correlation between nutrient intakes and immune‐inflammation indicators and to assess their performance in distinguishing immune‐inflammation states.MethodsThis study was derived from the National Health and Nutrition Examination Survey (NHANES), which included 33,804 participants aged 20 years or older between 2005 and 2018. Multivariable linear regression and restricted cubic spline regression were conducted to evaluate the association between nutrient intakes and immune‐inflammation indicators. Receiver operating characteristic curve analysis was performed to evaluate the discriminatory performance of identified nutrients for various immune‐inflammation states measured by the systemic immune‐inflammation index (SII).ResultsTen key nutrients were significantly associated with immune‐inflammation responses, including calcium, saturated fatty acid (SFA) 4:0, SFA 6:0, SFA 12:0, SFA 14:0, SFA 16:0, vitamin B2, total SFAs, retinol, and lutein + zeaxanthin, which show potential as dietary indicators. The area under the curve for discriminating various immune‐inflammation states was improved by at least 0.03 compared with a model that included only covariates, with all P values <0.05 in the Delong tests, indicating a significant enhancement in model performance.ConclusionsTen nutrients, including calcium, various SFAs, vitamin B2, retinol, and lutein + zeaxanthin, exhibit significant association with SII and potential as dietary indicators for distinguishing between different immune‐inflammation states in US adults with seropositivity to various viruses.
The impact of intravenous versus submucosal dexamethasone on short‐term patient response: A randomized controlled trial
Authors: Pearce Ellen P. , Deas David E. , Powell Charles A. , Diogenes Anibal , Kotsakis Georgios A. , Mader Michael J. , Palaiologou Archontia 
Published: October 2024

AbstractBackgroundThe purpose of this randomized, cross‐over trial was to determine if a preoperative dose of dexamethasone administered submucosally is as effective as intravenous (IV) dexamethasone in reducing pain, swelling, and analgesic consumption after periodontal flap surgery.MethodsThirty‐nine patients planned for two similar flap surgeries under IV sedation were included. Before the first surgery, patients were randomized to receive 8 mg of IV or submucosal dexamethasone. Via the alternate route, 0.9% sodium chloride (placebo) was administered. Dexamethasone was administered via the opposite route during the second surgery. A standardized regimen of 600 mg ibuprofen and 325 mg acetaminophen was used to manage postoperative pain. Patients recorded pain and swelling levels on a 21‐point numerical rating scale (NRS‐21) and a four‐point visual rating scale (VRS‐4), as well as analgesic usage via a phone application at 12, 24, 48, 72, and 168 h postoperatively.ResultsWhile NRS‐21 and VRS‐4 data suggest a trend toward decreased pain and swelling with IV administration, there were no significant differences in analgesic usage or pain at any time and a significant difference in swelling only at 72 h in favor of IV administration (p = 0.047).ConclusionsThere was no significant difference in pain or analgesic usage following periodontal flap surgery comparing IV and submucosal dexamethasone. A statistically significant difference in swelling between groups at 72 h is likely of limited clinical relevance. Submucosal dexamethasone is an effective way to mitigate pain following periodontal surgery, particularly when IV access for sedation is not required.
Higher skin sympathetic nerve activity as a potential predictor of overactive bladder in females refractory to oral monotherapy
Authors: Chen Yu‐Chen , Chen Hao‐Wei , Huang Tien‐Chi , Lee Chien‐Hung , Chu Ting‐Yin , Juan Yung‐Shun , Liu Yu‐Peng , Tsai Wei‐Chung , Wu Wen‐Jeng 
Published: October 2024

AbstractThis study investigates predictors of unsatisfactory outcomes in female overactive bladder (OAB) patients treated with oral monotherapy by analyzing skin sympathetic nerve activity (SKNA) using a novel “neuECG” method. The study included 55 newly diagnosed female patients with idiopathic OAB, autonomic function was evaluated using neuECG before treatment initiation, and validated OAB questionnaires and urodynamic studies were administered. Initial monotherapy was administered for the first 4 weeks, with non‐responders defined as patients not achieving satisfactory symptom relief and requiring further treatment. Responders (n = 32) and non‐responders (n = 23) had no significant differences in baseline characteristics or urodynamic parameters; however, non‐responders exhibited significantly higher baseline average SKNA (aSKNA) (1.36 ± 0.49 vs. 0.97 ± 0.29 μV, p = 0.001), higher recovery aSKNA (1.28 ± 0.46 vs. 0.97 ± 0.35 μV, p = 0.007), and a lower stress/baseline ratio of aSKNA (1.05 ± 0.42 vs. 1.26 ± 0.26, p = 0.029). Baseline aSKNA had the highest predictive value for monotherapy refractoriness in OAB (AUROC = 0.759, p = 0.001), with an optimal cut‐off point of >1.032 μV. These findings suggest that elevated pre‐treatment aSKNA can predict resistance to oral monotherapy in OAB, warranting close monitoring and proactive treatment strategies for patients with high aSKNA.
Viability of Free Bone Graft in Combination With Free Tissue Transfer and Post‐Operative RT in Orbital Floor Reconstruction
Authors: Chakrabarti Swagnik , Phad Avadhut Tukaram , Shetty Chaitra , Ghosh Abhishek 
Published: October 2024

Objectives/AimOrbital floor reconstruction post cancer ablation is challenging especially when associated with extensive soft tissue defects. Due consideration is to be given to the possible toxicities of adjuvant radiotherapy as well. Free bone‐soft tissue flaps are ideally suited in such situations. However, a single flap may fall inadequate for large defects. Using two free flaps in combination increases operating time and donor site morbidities. Non‐vascularized bone grafts combined with large soft tissue flaps harbor the risk of bone resorption and osteo‐radio necrosis. Alloplastic implants can lead to exposure and infection. We conducted a study researching the outcome of non‐vascularized cortico‐cancellous iliac bone graft (NVCIBG) used in orbital floor reconstruction along with free anterolateral thigh (FALT) flap in subjects undergoing extensive surgical ablation and adjuvant radiotherapy.Materials and MethodsTen consecutive subjects who underwent maxillo‐mandibular resection with or without skin were included in the study. The parameters assessed were diplopia, ectropion, bone viability, and osteointegration. Subjects were assessed in the immediate post‐operative period, 1 month after surgery, and after 1 year of radiotherapy.ResultsThe size of iliac bone harvested ranged from 3 to 5.5 cm (mean 4.8 cm). Forty percent subjects complained of binocular diplopia in the initial post‐operative period which subsided subsequently. Thirty percent subjects developed ectropion all of whom required external skin reconstruction. None developed osteoradionecrosis.ConclusionNVCIBG along with FALT flap is an excellent reconstructive option for orbital floor defects. It can withstand the toxicities of adjuvant radiotherapy and avoids the need for double free flap reconstruction.Level of Evidence4 Laryngoscope, 135:1072–1077, 2025