bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between visual field index and quality of life in glaucoma patients: a new tool to screen quality of life perception?
Authors: Rossi Gemma Caterina Maria , Milano Giovanni , De Silvestri Annalisa , Savini Lorenzo , Bosi Chiara , Gambini Giulia , Rama Paolo 
Published: September 2023

PurposeTo evaluate the correlation between the visual field index (VFI) and vision-related quality of life (QoL) considering several confounding variables that may have a positive or negative effect.MethodsWe conducted a cross-sectional, mono-centric study on glaucoma patients. Quality of life was examined with the NEI-VFQ 25 and the Glaucoma Symptom Scale (GSS). The visual field was examined with the Humphrey Field Analyzer. The variables considered were age, gender, comorbidities, years (at diagnosis and duration of the illness), treatment and related active principles, intraocular pressure, and visual acuity. The analysis was performed on both the better and the worse eye. The linear regression univariate analysis and the multivariate analyses were performed.ResultsIn total, 193 patients enrolled in the study. The mean age was 70.8 ± 10.4 years. The mean follow-up period since diagnosis 11.4 ± 9.2 years. Approximately 50% of the patients suffered from primary open angle glaucoma (POAG) and 45% were on monotherapy. The mean VFI was 81.3 ± 26. Regarding QoL, the NEI-VFQ total mean was 80.4 ± 17.8 and the GSS total score was 77.2 ± 21. Regarding NEI-VFQ 25, the single linear regression analysis found the following relations: age at time of visit (r = −0.30, p = 0.016), years of illness (r = −0.32, p = 0.020), the minimum and maximal visual acuity (r = 2.04 and r = 3.96, p &lt; 0.001), the IOP min (r = 1.13, p = 0.002) and max (r = −0.52, p = 0.017), and the number of previous surgeries (r = −3.94, p &lt; 0.001). The multivariate analysis found the following relations: gender (r = 5.13, p = 0.019), visual acuity max (r = 3.16, p &lt; 0.001), and previous surgeries (r = −1.80, p = 0.032). Regarding GSS, the single linear regression analysis found relations with visual acuity (r = 2.37, p &lt; 0.001), VFI (r = 0.41, p &lt; 0.001), previous surgeries in the eye considered (r = −7.27, p &lt; 0.001), and number of instillations (r = −3.67, p = 0.031). Data confirmed that a higher VFI has a positive impact on the score of both the NEI-VFQ 25 (r = 0.22, p = &lt; 0.001) and the GSS questionnaire (r = 0.36, p &lt; 0.001).ConclusionsThe study demonstrated a correlation between the VFI and QoL of patients and their visual and non-visual ocular symptoms and function both in the worst and in the better eye, even when accounting for several clinical and demographic confounding variables. Our data support that the visual field index is an important metric instrument in the follow up of patients with glaucoma.
Combining metal nanoparticles and nanobodies to boost the biomedical imaging in neurodegenerative diseases
Authors: Sanna A. , Quarta A. , Pieroni N. , Parodi B. , Palermo F. , Bukreeva I. , Fratini M. , Massimi L. , Simeone D. , Le Guével X. , Bravin A. , Quintiero E. , Viola I. , Gigli G. , Kerlero de Rosbo N. , Sancey L. , Cedola A. 
Published: September 2023

Introduction: In the study of neurodegenerative diseases, the possibility to follow the fate of specific cells or molecules within the whole body would be a milestone to better understand the complex evolution of disease mechanisms and to monitor the effects of therapies. The techniques available today do not allow the visualization of disease-relevant cells within the whole tridimensional biological context at high spatial resolution.Methods: Here we show the results from the first validation steps of a novel approach: by combining the conjugate nanobodies anti-glial fibrillary acidic protein (GFAP) and metal-nanoparticles (i.e. 2 nm gold NP) with X-ray phase contrast tomography (XPCT) we would be able to obtain a tridimensional visualization and identification of cells of interest together with the surrounding tissue and the vascular and neuronal networks.Results: By exploiting the X-ray attenuation properties of metal nanoparticles and the specific targeting capabilities of nanobodies, we could give XPCT the specificity it presently lacks, making it no longer a pure morphological but a molecular and targeted imaging technique. In our case, we synthesized and characterized Gold-NP/GFAP nanobody to target the astrocytes of mouse brain.Discussion: The results of the first tests presented in this paper have provided us with information on the feasibility of the approach, encouraging us to carry out further experiments in order to achieve the ultimate goal of setting up this new imaging technique.
Development and external validation of a nomogram for predicting postoperative pneumonia in aneurysmal subarachnoid hemorrhage
Authors: Jin Xiao , Wang Shijia , Zhang Chengwei , Yang Song , Lou Lejing , Xu Shuyao , Cai Chang 
Published: September 2023

BackgroundPostoperative pneumonia (POP) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) associated with increased mortality rates, prolonged hospitalization, and high medical costs. It is currently understood that identifying pneumonia early and implementing aggressive treatment can significantly improve patients' outcomes. The primary objective of this study was to explore risk factors and develop a logistic regression model that assesses the risks of POP.MethodsAn internal cohort of 613 inpatients with aSAH who underwent surgery at the Neurosurgical Department of First Affiliated Hospital of Wenzhou Medical University was retrospectively analyzed to develop a nomogram for predicting POP. We assessed the discriminative power, accuracy, and clinical validity of the predictions by using the area under the receiver operating characteristic curve (AUC), the calibration curve, and decision curve analysis (DCA). The final model was validated using an external validation set of 97 samples from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database.ResultsAmong patients in our internal cohort, 15.66% (n = 96/613) of patients had POP. The least absolute shrinkage and selection operator (LASSO) regression analysis identified the Glasgow Coma Scale (GCS), mechanical ventilation time (MVT), albumin, C-reactive protein (CRP), smoking, and delayed cerebral ischemia (DCI) as potential predictors of POP. We then used multivariable logistic regression analysis to evaluate the effects of these predictors and create a final model. Eighty percentage of patients in the internal cohort were randomly assigned to the training set for model development, while the remaining 20% of patients were allocated to the internal validation set. The AUC values for the training, internal, and external validation sets were 0.914, 0.856, and 0.851, and the corresponding Brier scores were 0.084, 0.098, and 0.143, respectively.ConclusionWe found that GCS, MVT, albumin, CRP, smoking, and DCI are independent predictors for the development of POP in patients with aSAH. Overall, our nomogram represents a reliable and convenient approach to predict POP in the patient population.
Predictive value of the Oxford Acute Severity of Illness Score in acute stroke patients with stroke-associated pneumonia
Authors: Wang Ximei , Xia Jianhua , Shan Yanhua , Yang Yang , Li Yun , Sun Haiyan 
Published: September 2023

BackgroundStroke-associated pneumonia (SAP) is associated with a poor prognosis and a high mortality rate in stroke patients. However, the accuracy of early prediction of SAP is insufficient, and there is a lack of effective prognostic evaluation methods. Therefore, in this study, we investigated the predictive value of the Oxford Acute Severity of Illness Score (OASIS) in SAP to provide a potential reference index for the incidence and prognosis of SAP.MethodsWe recruited a total of 280 patients with acute ischemic stroke who had been diagnosed and treated in the Zhumadian Central Hospital between January 2021 and January 2023. These patients were divided into an SAP group (86 cases) and a non-SAP group (194 cases) according to SAP diagnostic criteria by expert consensus on the diagnosis and treatment of SAP. We collated general and clinical data from all patients, including the survival of SAP patients during the follow-up period. Multivariate logistic regression was used to analyze the risk factors for SAP. Kaplan–Meier and multivariate COX regression analyses were used to investigate the relationship between OASIS and the prognosis of SAP, and a receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of OASIS for SAP.ResultsOur analyses identified body temperature, C-reactive protein, procalcitonin, OASIS, and a prolonged length of intensive care unit (ICU) stay as the main risk factors for SAP (all Ps &lt; 0.05). Advanced age and an elevated OASIS were identified as the main risk factors for death in SAP patients (all Ps &lt; 0.05). The risk of death in patients with OASIS of 31–42 points was significantly higher than that in patients with OASIS of 12–20 points (HR = 5.588, 95% CI = 1.531–20.401, P = 0.009). ROC curve analysis further showed that OASIS had a high predictive value for morbidity and the incidence of death in SAP patients.ConclusionOASIS can effectively predict the onset and death of SAP patients and provides a potential reference index for early diagnosis and the prediction of prognosis in patients with SAP. Our findings should be considered in clinical practice.
The effect of L-carnitine supplementation on lipid profile in adults: an umbrella meta-analysis on interventional meta-analyses
Authors: Musazadeh Vali , Alinejad Hanie , Esfahani Niloofar Kouhi , Kavyani Zeynab , Keramati Majid , Roshanravan Neda , Mosharkesh Erfan , Dehghan Parvin 
Published: September 2023

IntroductionPrevious meta-analyses investigating the therapeutic effects of L-carnitine on lipid profiles have demonstrated inconsistent results. The present umbrella meta-analysis aimed to investigate the impact of efficacy of L-carnitine on lipid profiles in adults.MethodsDatabases including PubMed, Scopus, and Embase, Web of Science, and Google Scholar were searched up to June 2023. Meta-analysis was performed using a random-effects model.ResultsOur results from thirteen meta-analyses indicated that L-carnitine supplementation significantly total cholesterol (TC) (ES = −1.05 mg/dL, 95% CI: −1.71, −0.39; p = 0.002), triglycerides (TG) (ES = −2.51 mg/dL; 95% CI: −3.62, −1.39, p &lt; 0.001), and low-density lipoprotein-cholesterol (LDL-C) (ES = −4.81 mg/dL; 95% CI: −6.04, −3.59; p &lt; 0.001). It also increased high-density lipoprotein-cholesterol (HDL-C) (ES: 0.66 mg/dL, 95% CI: 0.20, 1.12, p = 0.005) levels.ConclusionThe present umbrella meta-analysis suggests supplementation with L-carnitine in a dosage of more than 2 g/day can improve lipid profile. Thus, L-carnitine supplementation can be recommended as an adjuvant anti-hyperlipidemic agent.
Maternal inflammatory, lipid and metabolic markers and associations with birth and breastfeeding outcomes
Authors: Christensen Sophie Hilario , Rom Ane Lilleøre , Greve Tine , Lewis Jack Ivor , Frøkiær Hanne , Allen Lindsay H. , Mølgaard Christian , Renault Kristina Martha , Michaelsen Kim F. 
Published: September 2023

BackgroundConditions in utero influence intrauterine and postnatal infant growth and a few studies indicate that maternal inflammation and insulin resistance might affect birth and breastfeeding outcomes. Furthermore, hormones in human milk (HM) may influence infant appetite-regulation and thereby milk intake, but the associations are less understood.Objective(1) To investigate associations between maternal inflammatory, lipid and metabolic markers and birth and breastfeeding outcomes, and (2) to assess predictors of maternal inflammatory, lipid and metabolic markers in pregnancy.MethodsSeventy-one mother-infant dyads participating in the Mothers, Infants and Lactation Quality (MILQ) study were included in the present study. Fasting blood samples were collected around 28th gestational week, and HM samples at three time points from 1.0 to 8.5 months, where milk intake was assessed using 24-h test weighing. Maternal plasma inflammatory, lipid and metabolic markers included high-sensitive C-reactive protein (hs-CRP), tumor-necrosis factor-α (TNFα), interferon-γ (IFNγ), Interleukin (IL)-6, IL-8, high-, low-, and very-low-density lipoprotein (HDL, LDL, VLDL), total-cholesterol, triglycerides, leptin, adiponectin, insulin, C-peptide, the homeostasis model assessment of insulin resistance (HOMA-IR) and glucose concentration at t = 120 min following an oral glucose tolerance test. Of these, TNFα, IFNγ, IL-6, IL-8, leptin, adiponectin and insulin were also measured in HM samples.ResultsHDL in pregnancy was inversely associated with gestational age (GA) at birth and GA-adjusted birthweight z-score, whereas triglycerides and glucose (t = 120) were positively associated with GA-adjusted birthweight z-score. Higher hs-CRP, VLDL and triglycerides were associated with a higher placental weight. Furthermore, higher HDL, insulin, leptin and HOMA-IR were associated with longer duration of exclusive breastfeeding (EBF). Higher pre-pregnancy BMI was the main predictor of higher levels of hs-CRP, log-TNFα, leptin, insulin, C-peptide, and HOMA-IR.ConclusionMaternal lipid and metabolic markers influenced birthweight z-score and placental weight as well as duration of EBF. Furthermore, pre-pregnancy BMI and maternal age predicted levels of several inflammatory and metabolic markers during pregnancy. Our findings indicate that maternal lipid and metabolic profiles in pregnancy may influence fetal growth and breastfeeding, possibly explained by overweight and/or higher placental weight.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT03254329.
Methodological quality of radiomic-based prognostic studies in gastric cancer: a cross-sectional study
Authors: Jiang Tianxiang , Zhao Zhou , Liu Xueting , Shen Chaoyong , Mu Mingchun , Cai Zhaolun , Zhang Bo 
Published: September 2023

BackgroundMachine learning radiomics models are increasingly being used to predict gastric cancer prognoses. However, the methodological quality of these models has not been evaluated. Therefore, this study aimed to evaluate the methodological quality of radiomics studies in predicting the prognosis of gastric cancer, summarize their methodological characteristics and performance.MethodsThe PubMed and Embase databases were searched for radiomics studies used to predict the prognosis of gastric cancer published in last 5 years. The characteristics of the studies and the performance of the models were extracted from the eligible full texts. The methodological quality, reporting completeness and risk of bias of the included studies were evaluated using the RQS, TRIPOD and PROBAST. The discrimination ability scores of the models were also compared.ResultsOut of 283 identified records, 22 studies met the inclusion criteria. The study endpoints included survival time, treatment response, and recurrence, with reported discriminations ranging between 0.610 and 0.878 in the validation dataset. The mean overall RQS value was 15.32 ± 3.20 (range: 9 to 21). The mean adhered items of the 35 item of TRIPOD checklist was 20.45 ± 1.83. The PROBAST showed all included studies were at high risk of bias.ConclusionThe current methodological quality of gastric cancer radiomics studies is insufficient. Large and reasonable sample, prospective, multicenter and rigorously designed studies are required to improve the quality of radiomics models for gastric cancer prediction.Study registrationThis protocol was prospectively registered in the Open Science Framework Registry (https://osf.io/ja52b).
High frequency of WNT-activated medulloblastomas with CTNNB1 wild type suggests a higher proportion of hereditary cases in a Latin-Iberian population
Authors: Moreno Daniel Antunes , Bonatelli Murilo , Antoniazzi Augusto Perazzolo , de Paula Flávia Escremim , Leal Leticia Ferro , Garcia Felipe Antônio de Oliveira , de Paula André Escremim , Teixeira Gustavo Ramos , Santana Iara Viana Vidigal , Saggioro Fabiano , Neder Luciano , Valera Elvis Terci , Scrideli Carlos Alberto , Stavale João , Malheiros Suzana Maria Fleury , Lima Matheus , Hajj Glaucia Noeli Maroso , Garcia-Rivello Hernan , Christiansen Silvia , Nunes Susana , Gil-da-Costa Maria João , Pinheiro Jorge , Martins Flavia Delgado , Junior Carlos Almeida , Mançano Bruna Minniti , Reis Rui Manuel 
Published: September 2023

PurposeMedulloblastomas are the most common primary malignant brain tumors in children. They are divided into molecular subgroups: WNT-activated, SHH-Activated, TP53 mutant or wild type, and non-WNT/non-SHH (Groups 3 and 4). WNT-activated medulloblastomas are usually caused by mutations in the CTNNB1 gene (85%–90%), and most remaining cases of CTNNB1 wild type are thought to be caused by germline mutations in APC. So far, the frequencies of CTNNB1 have been reported mainly in North American and European populations. The aim of this study was to report the frequency of CTNNB1 mutations in WNT-activated medulloblastomas in a Latin-Iberian population and correlate with their clinicopathological characteristics.MethodsA total of 266 medulloblastomas from seven different institutions from Brazil (n=211), Portugal (n=38), and Argentina (n=17) were evaluated. Following RNA and DNA isolation from formalin-fixed, paraffin-embedded (FFPE) tumor tissues, the molecular classification and CTNNB1 mutation analysis were performed by nCounter and Sanger sequencing, respectively.ResultsWNT-activated medulloblastomas accounted for 15% (40/266) of the series. We observed that 73% of WNT-activated medulloblastomas harbored CTNNB1 mutations. CTNNB1 wild-type cases (27%) were more prevalent in female individuals and suggested to be associated with a worse outcome. Among the CTNNB1 wild-type cases, the available analysis of family history revealed two cases with familiar adenomatous polyposis, harboring APC germline variants.ConclusionWe observed a lower incidence of CTNNB1 mutations in WNT-activated medulloblastomas in our Latin-Iberian cohort compared to frequencies previously described in other populations. Considering that CTNNB1 wild-type cases may exhibit APC germline mutations, our study suggests a higher incidence (~30%) of hereditary WNT-activated medulloblastomas in the Latin-Iberian population.
Clinical outcomes of ramucirumab plus docetaxel in the treatment of patients with non-small cell lung cancer after immunotherapy: a systematic literature review
Authors: Garon Edward B. , Visseren-Grul Carla , Rizzo Maria Teresa , Puri Tarun , Chenji Suresh , Reck Martin 
Published: September 2023

IntroductionIn the REVEL trial, ramucirumab plus docetaxel demonstrated significant improvements in overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) compared with placebo plus docetaxel for treatment of metastatic non-small cell lung cancer (NSCLC) that progressed during or after platinum-based chemotherapy. Since the approval of ramucirumab plus docetaxel, immune checkpoint inhibitors (ICIs), either as single agents or in combination with chemotherapy, have become the standard of care for first-line treatment of patients with advanced NSCLC. However, efficacy and safety data for ramucirumab plus docetaxel after prior ICI treatment from randomized controlled clinical studies are lacking.MethodsFollowing Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic literature review was performed. Electronic databases and select international oncology conference proceedings were searched. Studies published between 01 January 2014 and 01 July 2022, which evaluated 2 efficacy outcomes (and included at least 1 time-to-event endpoint) or safety outcomes of ramucirumab plus docetaxel in NSCLC that progressed after prior ICI treatment, were identified. Twelve studies were included in the analysis. Two treatment groups were selected: ramucirumab plus docetaxel after prior ICI ± chemotherapy (RAM + DTX ICI pre-treated) and ramucirumab plus docetaxel after prior chemotherapy only (RAM + DTX ICI naïve). OS, PFS, ORR, disease control rate (DCR), and safety data were extracted and descriptively summarized across both treatment groups.ResultsThe pooled weighted median PFS and median OS were 5.7 months (95% confidence interval [CI]: 3.9-6.8) and 11.2 months (95% CI: 7.5-17.5), respectively, in the RAM + DTX ICI pre-treated group and 3.8 months (95% CI: 2.3-4.1) and 13.5 months (95% CI: 8-24.0), respectively, in the RAM + DTX ICI naïve group. The ORR and DCR ranged from 20.9% to 60.0% and from 62.4% to 90.0%, respectively, in the RAM + DTX ICI pre-treated group and from 17.7% to 20.0% and from 57.1% to 75.0%, respectively, in the RAM + DTX ICI naïve group. The safety profile across studies was consistent between both treatment groups, and no new safety signals were reported.ConclusionsCumulatively, these results support the combination of ramucirumab plus docetaxel as an effective and safe subsequent therapy for the treatment of patients with metastatic NSCLC with disease progression irrespective of previous ICI treatment.
Case report: Diagnosis of a patient with Sifrim–Hitz–Weiss syndrome, development and epileptic encephalopathy-14, and medium chain acyl-CoA dehydrogenase deficiency
Authors: Zeka Naim , Zeka Eris , Zhubi Esra , Hoxha Ilir 
Published: September 2023

BackgroundIt is generally recognized that genetic metabolic disorders can result in neurological symptoms such as seizures, developmental delay, and intellectual disability. Heterogeneous clinical presentations make the diagnosis challenging.Case presentationIn this case report, we present a unique and complex genetic disorder observed in a female patient who exhibited three pathogenic gene variants in the KCNT1, ACADM, and CHD4 genes. The convergence of these variants resulted in a multifaceted clinical presentation characterized by severe seizures of combined focal and generalized onset, metabolic dysfunction, and neurodevelopmental abnormalities. The identification and functional characterization of these gene variants shed light on the intricate interplay between these genes and the patient's phenotype. EEG revealed an epileptiform abnormality which presented in the inter-ictal period from the left frontal-central area and in the ictal period from the left mid-temporal area. The brain MRI revealed volume loss in the posterior periventricular area and parietal parenchyma, myelin destruction with no sign of hypoxic involvement, and left dominant enlargement of the lateral ventricles secondary to loss of central parenchyma. The patient was diagnosed through exome sequencing with Sifrim–Hitz–Weiss syndrome, development and epileptic encephalopathy-14, and medium-chain acyl-CoA dehydrogenase deficiency. An antiseizure medication regimen with valproic acid, levetiracetam, phenobarbital, and clonazepam was initiated. However, this led to only partial control of the seizures.ConclusionClinical follow-up of the patient will further define the clinical spectrum of KCNT1, ACADM, and CHD4 gene variants. It will also determine the long-term efficacy of the treatment of seizures and the development of precision medicine for epilepsy syndromes due to gain-of-function variants. Special emphasis should be put on the role and importance of large-scale genomic testing in understanding and diagnosing complex phenotypes and atypical epileptic syndromes.