bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation in Luminescence Characteristics and Paramagnetic Defect Centres in Fine-Grained Quartz From a Loess-Palaeosol Sequence in Tajikistan: Implications for Provenance Studies in Aeolian Environments
Authors: Dave Aditi K. , Timar-Gabor Alida , Scardia Giancarlo , Safaraliev Nosir , Fitzsimmons Kathryn E. 
Published: May 2022

Trapped charge characteristics in quartz are of increasing interest for their utility as indicators of sediment provenance. These include sensitivity of optically stimulated luminescence (OSL) and thermoluminescence (TL) signal and paramagnetic E1’ defect centre in quartz. Up until now, these methods have largely been used independently in provenance investigations, especially in aeolian systems. Variations in quartz OSL and TL signal sensitivity in loess-palaeosol sequences has been linked to shifts in sediment source corresponding to climatic fluctuations. However, the processes responsible for observed variation in OSL and TL sensitivity in quartz, including its link to the original rock source and/or its sedimentary history, remains a topic of contention. On the other hand, the intensity of E1’ defect centre in quartz is known to reflect the provenance of quartz, and is also routinely utilised as a provenance indicator in aeolian studies. In this study we aim to understand the variations in E1’ intensity and OSL (and TL) sensitivity by direct comparison of these characteristics in fine-grained quartz from a c. 60 m-thick loess-palaeosol sequence in Tajikistan. In doing so, we investigate the natural processes that may have led to variability in trapped-charge characteristics over the c. 500 ky timespan covered by the sequence. Our results suggest that apart from the inherent link to its provenance signature, the observed luminescence sensitivity of quartz especially in loess-palaeosol sequences are largely influenced by depositional and post-depositional processes during soil formation.
Glacial-Interglacial Variations in Organic Carbon Burial in the Northwest Pacific Ocean Over the Last 380 kyr and its Environmental Implications
Authors: Zhang Yuying , Hu Limin , Wu Yonghua , Dong Zhi , Yao Zhengquan , Gong Xun , Liu Yanguang , Ikehara Minoru , Shi Xuefa 
Published: May 2022

The carbon cycle on the Earth’s surface is linked to long-term variations in atmospheric CO2 as well as carbon sequestration in various pools. The burial of particulate organic carbon (OC) in marine sediments is also highly sensitive to the global climate over geological time scales, but with little known about OC burial and its regulations over glacial-interglacial cycles. Here, we present a long-term OC record over the past ∼380 kyr, from the Northwest Pacific Ocean, an ideal region for studying OC burial and its environmental implications on glacial-interglacial timescales. We observed a distinct cyclicity of higher OC burial in glacial periods, which was coupled with input from Asian dust and the Kuroshio Current but seemingly decoupled from biogenic element contents, implying a limited effect of marine productivity on OC burial. Moreover, the sedimentary record of OC was synchronous with oceanic redox conditions, especially the redox sensitive elements at the sediment-water interface, indicating a relatively reducing conditions that enhanced OC preservation during glacial periods. The overall glacial-interglacial OC burial regime in the Northwest Pacific Ocean was conceptually constructed. It showed a higher efficiency of OC burial during glacial periods and significant degradation during interglacial periods. The findings of this study highlighted the important contribution of environmental redox conditions on OC burial in the deep Northwest Pacific, demonstrating the sensitivity of the carbon cycle to global climate on an orbital scale.
Mathematical Modeling of Free Thyroxine Concentrations During Methimazole Treatment for Graves’ Disease: Development and Validation of a Computer-Aided Thyroid Treatment Method
Authors: Theiler-Schwetz Verena , Benninger Thomas , Trummer Christian , Pilz Stefan , Reichhartinger Markus 
Published: May 2022

BackgroundMethimazole (MMI) is the first-line treatment for patients with Graves’ disease (GD). While there are empirical recommendations for initial MMI doses, there is no clear guidance for subsequent MMI dose titrations. We aimed to (a) develop a mathematical model capturing the dynamics of free thyroxine (FT4) during MMI treatment (b), validate this model by use of numerical simulation in comparison with real-life patient data (c), develop the software application Digital Thyroid (DigiThy) serving either as a practice tool for treating virtual patients or as a decision support system with dosing recommendations for MMI, and (d) validate this software framework by comparing the efficacy of its MMI dosing recommendations with that from clinical endocrinologists.MethodsBased on concepts of automatic control and by use of optimization techniques, we developed two first order ordinary differential equations for modeling FT4 dynamics during MMI treatment. Clinical data from patients with GD derived from the outpatient clinic of Endocrinology at the Medical University of Graz, Austria, were used to develop and validate this model. It was subsequently used to create the web-based software application DigiThy as a simulation environment for treating virtual patients and an autonomous computer-aided thyroid treatment (CATT) method providing MMI dosing recommendations.ResultsBased on MMI doses, concentrations of FT4, thyroid-stimulating hormone (TSH), and TSH-receptor antibodies (TRAb), a mathematical model with 8 patient-specific constants was developed. Predicted FT4 concentrations were not significantly different compared to the available consecutively measured FT4 concentrations in 9 patients with GD (52 data pairs, p=0.607). Treatment success of MMI dosing recommendations in 41 virtually generated patients defined by achieved target FT4 concentrations preferably with low required MMI doses was similar between CATT and usual care. Statistically, CATT was significantly superior (p&lt;0.001).ConclusionsOur mathematical model produced valid FT4 predictions during MMI treatment in GD and provided the basis for the DigiThy application already serving as a training tool for treating virtual patients. Clinical trial data are required to evaluate whether DigiThy can be approved as a decision support system with automatically generated MMI dosing recommendations.
Sex Cord-Stromal Tumors of Testis: A Clinicopathologic and Follow-Up Study of 15 Cases in a High-Volume Institute of China
Authors: Huang Yin , Chen Bo , Cao Dehong , Chen Zeyu , Li Jin , Guo Jianbing , Dong Qiang , Wei Qiang , Liu Liangren 
Published: May 2022

ObjectivesTo report the first series of testicular sex cord-stromal tumors (TSCSTs) with detailed clinicopathologic findings and long-term follow-up in the Chinese population.Patients and MethodsFrom 2008 to 2018, 15 patients with TSCST were included in our study. The tumors were analyzed for epidemiological parameters, clinical characteristics, tumor markers, therapy, and follow-up data.ResultsThe median age of the patients was 28 years (range, 13–80 years). Para-aortic lymph node metastases were detected in 2 patients after radiological evaluation. Orchiectomy was performed in all patients, and the median diameter of the tumor was 1.5 cm (range, 0.5–5.0 cm). Nine Leydig cell tumors (LCTs), 5 Sertoli cell tumors (SCTs), and 1 unclassified type were confirmed after pathologic evaluation. Thirteen patients (86.7%) were categorized as stage I, and 2 patients (13.3%) were categorized as stage II. The median clinical follow-up was 39.0 months (range, 5–97 months), which showed 10 alive patients, such as 1 patient with progression at 40 months after orchiectomy. The 3- and 5-year progression-free survivals were 100 and 90.0%, respectively.ConclusionTesticular sex cord-stromal tumor at stages I and II is a rare subtype with benign behavior and a favorable prognosis in the Chinese population. However, lymph node metastases may be the dominant risk factor for patients with TSCST.
Building Efficient CNN Architectures for Histopathology Images Analysis: A Case-Study in Tumor-Infiltrating Lymphocytes Classification
Authors: Meirelles André L. S. , Kurc Tahsin , Kong Jun , Ferreira Renato , Saltz Joel H. , Teodoro George 
Published: May 2022

BackgroundDeep learning methods have demonstrated remarkable performance in pathology image analysis, but they are computationally very demanding. The aim of our study is to reduce their computational cost to enable their use with large tissue image datasets.MethodsWe propose a method called Network Auto-Reduction (NAR) that simplifies a Convolutional Neural Network (CNN) by reducing the network to minimize the computational cost of doing a prediction. NAR performs a compound scaling in which the width, depth, and resolution dimensions of the network are reduced together to maintain a balance among them in the resulting simplified network. We compare our method with a state-of-the-art solution called ResRep. The evaluation is carried out with popular CNN architectures and a real-world application that identifies distributions of tumor-infiltrating lymphocytes in tissue images.ResultsThe experimental results show that both ResRep and NAR are able to generate simplified, more efficient versions of ResNet50 V2. The simplified versions by ResRep and NAR require 1.32× and 3.26× fewer floating-point operations (FLOPs), respectively, than the original network without a loss in classification power as measured by the Area under the Curve (AUC) metric. When applied to a deeper and more computationally expensive network, Inception V4, NAR is able to generate a version that requires 4× lower than the original version with the same AUC performance.ConclusionsNAR is able to achieve substantial reductions in the execution cost of two popular CNN architectures, while resulting in small or no loss in model accuracy. Such cost savings can significantly improve the use of deep learning methods in digital pathology. They can enable studies with larger tissue image datasets and facilitate the use of less expensive and more accessible graphics processing units (GPUs), thus reducing the computing costs of a study.
Gender Differences in Levodopa Pharmacokinetics in Levodopa-Naïve Patients With Parkinson’s Disease
Authors: Conti Valeria , Izzo Viviana , Russillo Maria Claudia , Picillo Marina , Amboni Marianna , Scaglione Cesa L. M. , Nicoletti Alessandra , Cani Ilaria , Cicero Calogero E. , De Bellis Emanuela , Charlier Bruno , Giudice Valentina , Somma Gerardina , Corbi Graziamaria , Barone Paolo , Filippelli Amelia , Pellecchia Maria Teresa 
Published: May 2022

BackgroundLevodopa (LD) is the most effective drug in the treatment of Parkinson’s disease (PD). Unfortunately, prolonged use of LD leads to complications, mainly motor/non-motor fluctuations (MNMF) and dyskinesias (DYS). Women seem more prone to develop such LD-related complications. Nonetheless, there is a paucity of prospective studies examining gender-related predictors of MNMF and DYS. Among several factors, which concur with a very complex scenario, changes in LD pharmacokinetics influence the drug’s effectiveness. The present study aimed to assess gender-related differences in LD pharmacokinetics in patients with PD at their first-ever intake of LD.Materials and MethodsThis is a multicentric study enrolling patients with PD, who were LD-naïve and received a single dose of LD/benserazide (100/25 mg) formulation. All participants gave their written informed consent, and the study was approved by the local Ethics Committees. To measure plasma LD concentrations and pharmacokinetic parameters (AUC, Cmax, Tmax, t1/2), fasting blood samples were collected before drug intake and then at 8-time points until 260 min. LD concentrations were measured by ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). Multiple linear regression analyses were performed to identify the predictors of the parameters.ResultsThirty-five patients (16 women and 19 men) were consecutively enrolled. Area under curve (AUC) and maximum plasma concentration (Cmax) were significantly higher in women than men (p = 0.0006 and p = 0.0014, respectively). No statistically significant difference was found regarding Tmax and t1/2. Multiple linear regression analyses revealed that female sex (β = 1.559116, 95% CI 0.8314479 2.286785; p &lt; 0.0001) and body mass index (BMI) (β = −0.0970631, 95% CI −0.1733004 −0.0208258; p = 0.014) significantly predicted AUC. Only female sex significantly predicted Cmax (β = 1,582.499, 95% CI 731.581 2,433.417; p = 0.001). Moreover, only BMI significantly predicted t1/2 (β = 0.0756267, 95% CI 0.0143407 0.1369126; p = 0.017). Stratifying by gender, BMI was confirmed to significantly predict t1/2 in women (β = 0.1300486, 95% CI 0.0172322 0.242865; p = 0.027), but not in men.ConclusionThis study provides novel insights on gender differences in LD pharmacokinetics, possibly contributing to the later development of motor complications and dyskinesia in PD.
Comparison of Intravitreal Anti-VEGF Agents With Laser Photocoagulation for Retinopathy of Prematurity of 1,627 Eyes in China
Authors: Linghu Dandan , Cheng Yong , Zhu Xuemei , Deng Xun , Yin Hong , Jiang Yanrong , Zhao Mingwei , Li Xiaoxin , Liang Jianhong 
Published: May 2022

PurposeTo compare the efficacies and treatment outcomes of intravitreal anti-VEGF agents and laser therapy in retinopathy of prematurity (ROP).MethodsA retrospective, non-randomized, comparative study of patients diagnosed with type 1 ROP or aggressive posterior ROP (A-ROP) treated with intravitreal anti-VEGF agents or laser therapy as primary treatment at the People's Hospital of Peking University.ResultsA total of 1,627 eyes of 862 patients were included. In Group 1, 399 eyes of 204 patients were diagnosed with A-ROP or zone I type 1 ROP. The initial regression of the anti-VEGF subgroup was better than that of the laser subgroup, and the reactivation rate and rate of progression to retinal detachment were lower than those of the laser subgroup. In Group 2, 1,228 eyes of 658 patients were diagnosed with zone II type 1 ROP. The reactivation rate of the laser subgroup was lower than that of the anti-VEGF subgroup. No significant differences were found in the initial regression and the probability of developing retinal detachment. Among the anti-VEGF agents, the reactivation rate in eyes treated with conbercept was much lower than that in eyes treated with ranibizumab. The spherical power and spherical equivalents of eyes treated with laser were significantly higher than those of eyes treated with anti-VEGF agents 1 year after initial treatment.ConclusionsIn contrast to laser therapy, anti-VEGF agents as primary treatments have potential advantages for eyes with zone I type 1 ROP and A-ROP. For eyes with zone II type 1 ROP, laser photocoagulation and anti-VEGF agents therapy showed similar efficacy; however, the rate of reactivation with laser therapy was significantly lower than that with anti-VEGF agents. Among the anti-VEGF agents, the reactivation rate was much lower in eyes treated with conbercept than in eyes treated with ranibizumab. Compared to anti-VEGF agents, laser treated eyes had greater trend to myopia.
A Novel Prognostic Score Based on Artificial Intelligence in Hepatocellular Carcinoma: A Long-Term Follow-Up Analysis
Authors: Liu Xiaoli , Wang Xinhui , Yu Lihua , Hou Yixin , Jiang Yuyong , Wang Xianbo , Han Junyan , Yang Zhiyun 
Published: May 2022

ObjectiveT cell immunity plays an important role in anti-tumor effects and immunosuppression often leads to the development and relapse of cancer. This study aimed to investigate the effect of T cell numbers on the long-term prognosis of patients with hepatocellular carcinoma (HCC) and construct an artificial neural network (ANN) model to evaluate its prognostic value.MethodsWe enrolled 3,427 patients with HCC at Beijing Ditan Hospital, Capital Medical University, and randomly divided them into two groups of 1,861 and 809 patients as the training and validation sets, respectively. Cox regression analysis was used to screen for independent risk factors of survival in patients with HCC. These factors were used to build an ANN model using Python. Concordance index, calibration curve, and decision curve analysis were used to evaluate the model performance.ResultsThe 1-year, 3-year, 5-year, and 10-year cumulative overall survival (OS) rates were 66.9%, 45.7%, 34.9%, and 22.6%, respectively. Cox multivariate regression analysis showed that age, white blood cell count, creatinine, total bilirubin, γ-GGT, LDH, tumor size ≥ 5 cm, tumor number ≥ 2, portal vein tumor thrombus, and AFP ≥ 400 ng/ml were independent risk factors for long-term survival in HCC. Antiviral therapy, albumin, T cell, and CD8 T cell counts were independent protective factors. An ANN model was developed for long-term survival. The areas under the receiver operating characteristic (ROC) curve of 1-year, 3-year, and 5-year OS rates by ANNs were 0.838, 0.833, and 0.843, respectively, which were higher than those of the Barcelona Clinic Liver Cancer (BCLC), tumor node metastasis (TNM), Okuda, Chinese University Prognostic Index (CUPI), Cancer of the Liver Italian Program (CLIP), Japan Integrated Staging (JIS), and albumin–bilirubin (ALBI) models (P &lt; 0.0001). According to the ANN model scores, all patients were divided into high-, middle-, and low-risk groups. Compared with low-risk patients, the hazard ratios of 5-year OS of the high-risk group were 8.11 (95% CI: 7.0-9.4) and 6.13 (95% CI: 4.28-8.79) (P&lt;0.0001) in the training and validation sets, respectively.ConclusionHigh levels of circulating T cells and CD8 + T cells in peripheral blood may benefit the long-term survival of patients with HCC. The ANN model has a good individual prediction performance, which can be used to assess the prognosis of HCC and lay the foundation for the implementation of precision treatment in the future.
The Value of Hepatic Scintigraphy in the Diagnosis of Biliary Atresia
Authors: Chan Wing Ki , Chung Patrick Ho Yu , Wong Kenneth Kak Yuen 
Published: May 2022

IntroductionBiliary Atresia (BA) requires prompt diagnosis and surgical intervention to optimize its outcome. The aim of this study was to evaluate the accuracy of EHIDA in distinguishing between BA and other causes of cholestatic jaundice.MethodsThis was a retrospective study of all patients who underwent EHIDA in a tertiary center from 1997 to 2019. The sensitivity, specificity, Negative Predictive Value (NPV) and Positive Predictive Value (PPV) of EHIDA were evaluated. Factors that can potentially affect its accuracy were also analyzed.ResultsDuring the study period, 93 patients aged 10 to 110 days with cholestasis and suspected BA underwent EHIDA. The sensitivity and NPV were 91.2 and 85.3% while specificity and PPV were 80.6 and 88.1%. These results suggested that EHIDA is suboptimal in both diagnosing or excluding BA. Out of 59 patients who showed no tracer activities in the intestines after 24 h, 56 were subjected to surgical exploration and 52 (92.9%) were eventually diagnosed BA. The accuracy of EHIDA scan were different by the maturity of the patient, age at testing and severity of cholestasis.ConclusionsEHIDA has a limited accuracy and surgical exploration remains the gold standard to establish the diagnosis of BA. Potential confounding factors that may affect the accuracy of EHIDA were identified but require further studies with larger sample sizes to validate.
Pediatric Chronic Tracheostomy Care: An Evaluation of an Innovative Competency-Based Education Program for Community Health Care Providers
Authors: Shi Jenny Y. , Orkin Julia , Walsh Catharine M. , Chu Stephanie , Keilty Krista , McKay Sandra , Mocanu Cora , Qazi Adam , Ambreen Munazzah , Amin Reshma 
Published: May 2022

ObjectiveTo evaluate the immediate and sustained knowledge retention and sense of self-efficacy of homecare nurses following completion of a standardized competency-based tracheostomy education course. Safe discharge of children requiring tracheostomy with or without ventilation relies on the competence of homecare nurses.Study DesignPragmatic, randomized controlled trial of 44 homecare nurses. Participants were randomized into the intervention group (n = 21), which received the tracheostomy course, or the control group (n = 23), which received an enterostomy and vascular access course. Multiple-choice question (MCQ) knowledge assessments and self-efficacy questionnaires were administered to both groups pre-course and post-course at 6 week, 3 month, 6 month, and 12 month follow-ups.ResultsTwenty participants in the intervention group and 19 in the control group were included. Four withdrew from the study and two crossed over from the control into the intervention arm. The change in mean self-efficacy scores (total score = 100) was significantly higher in the intervention group than in the control group at 6 weeks (intervention (mean ± SD): 18.6 ± 14.5; control: 6.6 ± 20.4; p = 0.04) and 3 months (intervention: 19.6 ± 14.2; control: 5.2 ± 17.0; p = 0.007), and trended higher at 6 months (intervention: 18.0 ± 14.5; control: 6.9 ± 24.1; p = 0.1). The change in mean MCQ assessment scores (total score = 20) trended higher in the intervention group than in the control group at 6 weeks (intervention (mean ± SD): 1.8 ± 2.2; control: 1.6, ± 2.9; p = 0.8).ConclusionsHomecare nurses who attended the tracheostomy course demonstrated a higher sense of self-efficacy at long-term follow-up.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT04559932.