bluuebunny/crossref_metadata_2025_split huggingface dataset:
A higher ctDNA fraction decreases survival in regorafenib‐treated metastatic colorectal cancer patients. Results from the regorafenib's liquid biopsy translational biomarker phase II pilot study
Authors: Unseld Matthias , Belic Jelena , Pierer Kerstin , Zhou Qing , Moser Tina , Bauer Raimund , Piringer Gudrun , Gerger Armin , Siebenhüner Alexander , Speicher Michael , Heitzer Ellen , Prager Gerald W. 
Published: September 2020

AbstractThe predictive effect of circulating tumor DNA (ctDNA) in colorectal cancer (CRC) treatment is still highly discussed. The primary objective of our study was to investigate a possible prognostic/predictive value of ctDNA under regorafenib treatment. This prospective multicenter translational biomarker phase II pilot study enrolled 30 metastatic CRC patients (67% men, 33% women) treated with regorafenib. ctDNA was assessed in plasma before treatment start and at defined time points during administration. Measurement of tumor fraction as well as mutation and copy number analysis of CRC driver genes were performed by next‐generation sequencing approaches. Multivariate analyses for survival and treatment efficacy were adjusted to age, gender and Eastern Cooperative Oncology Group. Disease control rate was 30%. Median tumor fraction at baseline was 18.5% (0‐49.9). Mutations in CRC driver genes or genes involved in angiogenesis were identified in 25 patients (83.3%). KRAS mutations were detected in 13 of 14 KRAS‐positive tumors; in three patients without KRAS mutation in the respective tumors, acquired mutations as a consequence of prior anti‐EGFR treatment were detected. In a subset of patients, novel occurring mutations or focal amplifications were detected. A tumor fraction of 5% and higher at baseline was significantly associated with a decreased OS (P = .022; hazard ratio 3.110 (95% confidence interval: 1.2‐8.2). ctDNA is detectable in a high proportion of mCRC patients. Higher ctDNA levels are associated with survival among regorafenib treatment. Moreover, our data highlight the benefit of a combined evaluation of mutations and somatic copy number alterations in advanced cancer patients.
Multi‐feature fusion of deep networks for mitosis segmentation in histological images
Authors: Zhang Yuan , Chen Jin , Pan Xianzhu 
Published: September 2020

AbstractMitotic cell detection in pathological images is significant for predicting the malignancy of tumors and the intelligent segmentation of these cells. Overcoming human error generated by pathologists in reading the images while enabling fast detection through high computing power remains a very challenging task. In this study, we proposed a method that fuses handcrafted features and deep features to segment mitotic cells in whole‐slide images. The handcrafted feature extraction strategy was based on four measure indices of the Gray Level Co‐occurrence Matrix. The deep feature extraction strategy was based on natural image knowledge transfer. Finally, the two strategies were fused to classify and distinguish the image pixels for the segmentation of mitotic cells. We used the AMIDA13 dataset and the pathological images collected by the Department of Pathology of Anhui No. 2 Provincial People's Hospital as the experimental dataset. We compared the Areas Under Curve (AUC) of Receiver Operating Characteristic obtained through the handcrafted feature model, the improved deep feature model with knowledge transfer, the classic U‐NET model, and the proposed multi‐feature fusion model. The results showed that the AUC values of our proposed method had 0.07 and 0.05 improved to classic U‐NET model on test dataset and validation dataset respectively, while achieved the best segmentation performance and detected most of true‐positive cells, representing a breakthrough for clinical application. The experiments also indicated that the staining uniformity of pathological tissue impacted the model performance.
Glaucoma assessment from color fundus images using convolutional neural network
Authors: Elangovan Poonguzhali , Nath Malaya Kumar 
Published: September 2020

AbstractEarly detection and proper screening are essential to prevent vision loss due to glaucoma. In recent years, convolutional neural network (CNN) has been successfully applied to the color fundus images for the automatic detection of glaucoma. Compared to the existing automatic screening methods, CNNs have the ability to extract the distinct features directly from the fundus images. In this paper, a deep learning architecture based on a CNN is designed for the classification of glaucomatous and normal fundus images. An 18–layer CNN is designed and trained to extract the discriminative features from the fundus image. It comprises of four convolutional layers, two max pooling layers, and one fully connected layer. A two–stage tuning approach is proposed for the selection of suitable batch size and initial learning rate. The proposed network is tested on DRISHTI–GS1, ORIGA, RIM–ONE2 (release 2), ACRIMA, and large–scale attention–based glaucoma (LAG) databases. Rotation data augmentation technique is employed to enlarge the dataset. Randomly selected 70% of images are used for training the model and remaining 30% images are used for testing. An overall accuracy of 86.62%, 85.97%, 78.32%, 94.43%, and 96.64% are obtained on DRISHTI–GS1, RIM–ONE2, ORIGA, LAG, and ACRIMA databases, respectively. The proposed method has achieved an accuracy, sensitivity, specificity, and precision of 96.64%, 96.07%, 97.39%, and 97.74%, respectively, for ACRIMA database. Compared to other existing architectures, the proposed method is robust to Gaussian noise and salt–and–pepper noise.
Safety and efficacy of a novel home‐use device for light‐potentiated (LED) skin treatment
Authors: Guermonprez Cyprien , Declercq Lieve , Decaux Géraldine , Grimaud Jean‐Alexis 
Published: September 2020

AbstractSkin structure and function results from a dynamic interplay between dermal and epidermal cell types. Optimizing skin health through an effective and long‐lasting skin care regime therefore requires a global approach, encompassing various mechanisms to stimulate this interplay beyond the action scope of a classical topical solution. This study evaluates the impact of a novel home‐use device combining a topical serum, light‐emitting diodes and massage on the clinical signs of extrinsic skin aging. The innovative principle relies on potentiating the effect of active ingredients contained in the topical serum with visible and near infra‐red photons to prevent extracellular matrix degradation and promote its reconstruction. After in vitro and ex vivo investigations, a clinical study assessed the safety and efficacy of a daily treatment with the home‐use device for 28 days. A significant increases in skin density and radiance while reducing the wrinkles was obtained with no side effects.
Correlates related to follow‐up in a community engagement program in North Central Florida
Authors: Otufowora Ayodeji , Liu Yiyang , Varma Deepthi S. , Striley Catherine W. , Cottler Linda B. 
Published: September 2020

AbstractAimsThis analysis identifies the correlates of 60‐ and 120‐day telephone‐based study follow‐ups among community‐dwelling adults in North Central Florida.MethodsSix thousand three hundred and forty participants were recruited by Community Health Workers from the University of Florida′s community engagement program with a face‐to‐face baseline and two phone follow‐ups assessing indicators of health.ResultsPhysical disability versus none (adjusted odds ratio [aOR], 1.5; 95% confidence interval [CI], 1.2─1.9), high trust in research versus none (aOR, 1.5; 95% CI, 1.1─2.1), history of research participation versus none (aOR, 1.6; 95% CI, 1.3─2.0), having health insurance versus none (aOR, 1.4; 95% CI, 1.1─1.7), interest in research participation versus none (aOR, 1.8; 95% CI, 1.3─2.7), and no drug use versus drug use (aOR, 0.5; 95% CI, 0.3─0.9) significantly predicted completion of follow‐up.ConclusionsHealth and social factors such as disability, insurance, history of and interest in research, trust and no drug use significantly predicted completing two follow‐ups. These findings can facilitate efforts to minimize attrition in the research enterprise.
Modeling the Efficacy of Natalizumab in Multiple Sclerosis Patients Who Switch From Every‐4‐Week Dosing to Extended‐Interval Dosing
Authors: Chang Ih , Muralidharan Kumar Kandadi , Campbell Nolan , Ho Pei‐Ran 
Published: September 2020

AbstractNatalizumab is approved for multiple sclerosis treatment at a dose of 300 mg every 4 weeks. Extended‐interval dosing of natalizumab has been proposed as a strategy to mitigate the risk of progressive multifocal leukoencephalopathy, but the efficacy of extended‐interval dosing is not established. Previous models suggesting lower efficacy when initiating natalizumab treatment with extended‐interval dosing rather than every‐4‐week dosing are inconsistent with reports from clinical observations and real‐world studies conducted in patient populations switching to extended‐interval dosing after a period of receiving natalizumab every 4 weeks. Here, the efficacy of natalizumab extended‐interval dosing was modeled specifically in patients switching from every‐4‐week dosing to extended‐interval dosing. Published population pharmacokinetic/pharmacodynamic models were used to simulate the distribution of alpha‐4 integrin saturations for different body weight categories and dosing intervals (every 5, 6, 7, 8, 10, or 12 weeks). Generalized estimating equations relating alpha‐4 integrin saturation to probability of multiple sclerosis lesion or relapse were derived from RESTORE trial data, which included patients (n = 175) who discontinued natalizumab after being treated every 4 weeks for ≥1 year and had no relapses in the year before discontinuation. The model‐based simulations described indicate that every‐5‐week or every‐6‐week dosing is likely to maintain the efficacy of natalizumab, particularly at body weights <80 kg, in patients who switch after a period of stability on every‐4‐week dosing. The efficacy of natalizumab decreases as dosing intervals and body weight increase. Partial model validation was achieved in that observed outcomes in an independent clinical study were similar to those predicted by the models.
Echocardiographic evaluation of the elasticity of the ascending aorta in patients with essential hypertension
Authors: Song Xiang‐Ting , Fan Li , Yan Zi‐Ning , Rui Yi‐Fei 
Published: September 2020

AbstractBackgroundHypertension is the most common chronic disease and the most important risk factor for cardiovascular and cerebrovascular diseases. Atheroma and arteriosclerosis plays a key role in the occurrence and development of hypertension. The purpose of this study was to evaluate the elasticity of ascending aorta wall in patients with essential hypertension (EH) using M‐mode echocardiography.Materials and MethodsWe prospectively enrolled 54 EH patients and 51 healthy subjects (HS). They all underwent transthoracic echocardiography to measure ascending aorta inner diameters and brachial blood pressure measurement to calculate aortic elastic variables: compliance, distensibility, strain, stiffness index, and Peterson's elastic modulus. All participants also underwent bilateral carotid ultrasonographic examination.ResultsThere were no significant differences in age, sex, body mass index, blood lipids, blood glucose, and ascending aorta inner diameters between the two groups. We found neither intimal thickening nor plaque formation in the left or right carotid arteries in both groups. The aortic elastic properties were significantly impaired in EH patients compared with HS.ConclusionsEchocardiography can be used for the noninvasive evaluation of ascending aorta wall elasticity as an early screening technique. Subclinical arteriosclerosis appeared to occur in the ascending aorta of patients with essential hypertension even though carotid ultrasonography was normal.
Serum zinc concentrations and characteristics of zinc deficiency/marginal deficiency among Japanese subjects
Authors: Yokokawa Hirohide , Fukuda Hiroshi , Saita Mizue , Miyagami Taiju , Takahashi Yuichi , Hisaoka Teruhiko , Naito Toshio 
Published: September 2020

AbstractBackgroundStudies that have examined serum zinc deficiency/marginal deficiency in developed countries, including Japan, are still limited. The aim of this study was to assess serum zinc concentrations and associated characteristics among Japanese subjects.MethodsThis cross‐sectional study, conducted from September 2016 to December 2018, included 2056 eligible subjects who participated in a voluntary health checkup. Serum zinc concentration categories were defined as deficiency (<60 μg/dL), marginal deficiency (≥60 to <80 μg/dL), and normal (≥80 μg/dL). Serum zinc concentrations were compared between the first age category (<40 years) and other age categories with Dunnett's method. Trends in P‐values were estimated using the Jonckheere‐Terpstra test for continuous variables.ResultsThe proportions of subjects with deficiency and marginal deficiency were 0.4% and 46.0% in men, and 0.6% and 38.4% in women, respectively. The deficiency/marginal deficiency group had significantly lower lipid profiles and nutritional status, and a significantly lower proportion were non–daily drinkers in both genders. Older age was significantly associated with lower serum zinc concentration only in men.ConclusionsOur findings clarified a high proportion of serum zinc deficiency/marginal deficiency, especially in men, and suggest a possible association between serum zinc levels and nutritional status and alcohol consumption. It may be necessary to manage nutritional status, including zinc intake.
Effects of branched‐chain amino acids on postoperative tumor recurrence in patients undergoing curative resection for hepatocellular carcinoma: A randomized clinical trial
Authors: Hachiya Hiroyuki , Aoki Taku , Iso Yukihiro , Shimizu Takayuki , Tago Kazuma , Park Kyung Hwa , Sakuraoka Yuhki , Shiraki Takayuki , Mori Shozo , Kubota Keiichi 
Published: September 2020

AbstractBackground/PurposeNo effective postoperative adjuvant therapies have been established for patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the effect of oral administration of branched‐chain amino acids (BCAA) on the recurrence‐free survival (RFS) after hepatic resection in HCC patients.MethodsIn this randomized clinical trial, HCC patients undergoing curative resections were randomly assigned in a 1:1 ratio to the BCAA group or surgery‐alone group. The BCAA group received BCAA (Livact®) for up to 4 years. The primary endpoint was RFS. The secondary endpoint was overall survival (OS). Multivariate analysis was performed to detect the clinical characteristics significantly associated with RFS.ResultsBetween January 2010 and October 2014, 156 patients (75 in BCAA group and 81 in surgery‐alone group) were enrolled in the study. Of these, two patients were excluded from the efficacy analysis. Comparison of the survival curves by the log rank test demonstrated no significant difference in the RFS (P = .579) or OS (P = .268) between the BCAA and the control group. Multivariate analysis revealed that the RFS was significantly associated with age and number of tumors. A beneficial effect of BCAA on the RFS was found in patients younger than 72 years old with a HbA1c level of < 6.4%.ConclusionsOral BCAA supplementation could not reduce the risk of recurrence after hepatic resection in HCC patients; however, the results suggested that BCAA supplementation may be beneficial for selected patients who were younger and had mildly impaired glucose tolerance.
Determinants of suboptimal CD4+ T cell recovery after antiretroviral therapy initiation in a prospective cohort of acute HIV‐1 infection
Authors: Handoko Ryan , Colby Donn J , Kroon Eugène , Sacdalan Carlo , de Souza Mark , Pinyakorn Suteeraporn , Prueksakaew Peeriya , Munkong Chutharat , Ubolyam Sasiwimol , Akapirat Siriwat , Chiarella Jennifer , Krebs Shelly , Sereti Irini , Valcour Victor , Paul Robert , Michael Nelson L. , Phanuphak Nittaya , Ananworanich Jintanat , Spudich Serena ,   the SEARCH 010/RV254 Study Team
Published: September 2020

AbstractIntroductionUp to 30% of individuals treated with antiretroviral therapy (ART) during chronic HIV fail to recover CD4 counts to >500 cells/mm3 despite plasma viral suppression. We investigated the frequency and associations of suboptimal CD4 recovery after ART started during acute HIV infection (AHI).MethodsParticipants who started ART in Fiebig I to V AHI with ≥48 weeks of continuous documented HIV‐RNA < 50 copies/mL were stratified by CD4 count at latest study visit to suboptimal immune recovery (SIR; CD4 < 350 cells/mm3), intermediate immune recovery (IIR; 350 ≤ CD4 < 500) and complete immune recovery (CIR; CD4 ≥ 500). Clinical and laboratory parameters were assessed at pre‐ART baseline and latest study visit. Additional inflammatory and neurobehavioral endpoints were examined at baseline and 96 weeks.ResultsOf 304 participants (96% male, median 26 years old) evaluated after median 144 (range 60 to 420) weeks of ART initiated at median 19 days (range 1 to 62) post‐exposure, 3.6% (n = 11) had SIR and 14.5% (n = 44) had IIR. Pre‐ART CD4 count in SIR compared to CIR participants was 265 versus 411 cells/mm3 (p = 0.002). Individuals with SIR or IIR had a slower CD4 rate of recovery compared to those with CIR. Timing of ART initiation by Fiebig stage did not affect CD4 count during treatment. Following ART, the CD8+T cell count (p = 0.001) and CD4/CD8 ratio (p = 0.047) were lower in SIR compared to CIR participants. Compared to the CIR group at week 96, the combined SIR and IIR groups had higher sCD14 (p = 0.008) and lower IL‐6 (p = 0.04) in plasma, without differences in neuropsychological or psychiatric indices.ConclusionsDespite immediate and sustained treatment in AHI, suboptimal CD4 recovery occurs uncommonly and is associated with low pre‐ART CD4 count as well as persistent low CD8 count and CD4/CD8 ratio during treatment.
Early access to antiretroviral therapy versus standard of care among HIV‐positive participants in Eswatini in the public health sector: the MaxART stepped‐wedge randomized controlled trial
Authors: Khan Shaukat , Spiegelman Donna , Walsh Fiona , Mazibuko Sikhatele , Pasipamire Munyaradzi , Chai Boyang , Reis Ria , Mlambo Khudzie , Delva Wim , Khumalo Gavin , Zwane Mandisa , Fleming Yvette , Mafara Emma , Hettema Anita , Lejeune Charlotte , Chao Ariel , Bärnighausen Till , Okello Velephi 
Published: September 2020

AbstractIntroductionThe WHO recommends antiretroviral treatment (ART) for all HIV‐positive patients regardless of CD4 count or disease stage, referred to as “Early Access to ART for All” (EAAA). The health systems effects of EAAA implementation are unknown. This trial was implemented in a government‐managed public health system with the aim to examine the “real world” impact of EAAA on care retention and viral suppression.MethodsIn this stepped‐wedge randomized controlled trial, 14 public sector health facilities in Eswatini were paired and randomly assigned to stepwise transition from standard of care (SoC) to EAAA. ART‐naïve participants ≥18 years who were not pregnant or breastfeeding were eligible for enrolment. We used Cox proportional hazard models with censoring at clinic transition to estimate the effects of EAAA on retention in care and retention and viral suppression combined.ResultsBetween September 2014 and August 2017, 3405 participants were enrolled. In SoC and EAAA respectively, 12‐month HIV care retention rates were 80% (95% CI: 77 to 83) and 86% (95% CI: 83 to 88). The 12‐month combined retention and viral suppression endpoint rates were 44% (95% CI: 40 to 48) under SoC compared to 80% (95% CI: 77 to 83) under EAAA. EAAA increased both retention (HR: 1·60, 95% CI: 1·15 to 2·21,p = 0.005) and retention and viral suppression combined (HR: 4.88, 95% CI: 2.96 to 8.05,p < 0.001). We also identified significant gaps in current health systems ability to provide viral load (VL) monitoring with 80% participants in SoC and 66% in EAAA having a missing VL at last contact.ConclusionsThe observed improvement in retention in care and on the combined retention and viral suppression provides an important co‐benefit of EAAA to HIV‐positive adults themselves, at least in the short term. Our results from this “real world” health systems trial strongly support EAAA for Eswatini and countries with similar HIV epidemics and health systems. VL monitoring needs to be scaled up for appropriate care management.
Primary Site Identification of Soft‐Tissue Mass: Things to Know in MRI Assessment
Authors: Aoki Takatoshi , Fujisaki Akitaka , Terasawa Takashi , Hayashida Yoshiko , Todoroki Yo , Hirano Natsumi , Hisaoka Masanori , Sakai Akinori , Korogi Yukunori 
Published: September 2020

The spectrum of soft‐tissue mass is varied, including neoplastic and nonneoplastic/inflammatory lesions. However, soft‐tissue tumors have similar imaging findings and, therefore, the diagnosis of soft‐tissue mass is challenging. Although careful assessment of the internal characteristics on imaging can often narrow the differential diagnoses, the differential diagnosis may be out of the question if identification of the soft‐tissue mass origin is missed. The purpose of this article is to review the imaging findings and the essential anatomy to identify the primary site of the soft‐tissue mass, and discuss the associated potential pitfalls. In order not to fall into a pitfall, recognition of characteristic imaging findings indicating the origin of the soft‐tissue mass and anatomical knowledge of the normal tissue distribution are necessary.Level of Evidence5Technical Efficacy Stage3
Multiple organ injury on admission predicts in‐hospital mortality in patients with COVID‐19
Authors: Yan He , Lu Shanshan , Chen Liangpei , Wang Yufang , Liu Qiaomei , Li Dongsheng , Yan Xisheng , Yan Jie 
Published: September 2020

AbstractMultiorgan injury has been implicated in patients with coronavirus disease 2019 (COVID‐19). We aim to assess the impact of organ injury (OI) on prognosis according to the number of affected organs at admission. This is a retrospective cohort study of patients with confirmed COVID‐19 in Wuhan Third Hospital & Tongren Hospital of Wuhan University from February 17 to March 22, 2020. We classified the patients according to the presence and number of damaged organs (heart, liver, and kidney). The percentage of patients with no, one, two, or three organs affected was 59.75%, 30.46%, 8.07%, and 1.72%, respectively. With the increasing number of OI, there is a tendency of gradual increase regarding the white blood cell counts, neutrophil counts, levels of C‐reactive protein (CRP), lactate dehydrogenase, D‐dimer, and fibrinogen as well as the incidence of most complications. In a Cox regression model, individuals with OI, old age, and an abnormal level of CRP were at a higher risk of death compared with those without. Patients with three organ injuries had the highest mortality rate (57.9%; hazard ratio [HR] with 95% confidence interval [CI] vs. patients without OI: 22.31 [10.42–47.77], those with two [23.6%; HR = 8.68, 95% CI = 4.58–16.48], one [8.6%; HR = 3.1, 95% CI = 1.7–5.7], or no OI [2.6%]; p < .001). The increasing number of OI was associated with a high risk of mortality in COVID‐19 infection.