bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of agronomic management on rice grain quality Part IV: Sowing rate
Authors: Wood Rachael Maree , Dunn Brian W. , Waters Daniel L. E. , Blanchard Christopher L. , Mawson Andrew John , Oli Prakash
Published: September 2020

Background and objectives

There are no published data on the effect of sowing rate on rice grain quality traits of medium‐ and short‐grain cultivars within the Australian environment. Studies that have reported on the impact of sowing rate on grain quality in other rice growing regions have assessed differences between densities below 100 plants/m2, which is the minimum target for Australian grown rice. Furthermore, the cultivars evaluated were long‐grain cultivars only. The effect of sowing rate (25–150 kg/ha) on the quality traits of a short (YRK5)‐ and medium (Viand)‐grain rice cultivar was investigated over two seasons. Nitrogen (N) application was included in the study as the appropriate combination of sowing and N rate for maximum yield for both cultivars was unknown.

Findings

Sowing and N rate affected the number of grains per panicle and plants established per m2 of both cultivars; however, changes in these parameters did not affect crop yield. The number of grains per panicle affected thousand‐grain weight (TGW) and head rice yield (HRY; the percentage of grain that remains whole or at least 75% of the original length after milling), and the response differed between cultivars. Decreasing sowing rate increased the number of grains per panicle, reduced grain length and TGW, and slightly increased HRY in Viand. In YRK5, decreased sowing rate increased TGW and in season two reduced HRY. Protein content was negatively correlated with TGW and positively correlated with HRY. There were no consistent differences in the physicochemical and cooking parameters between densities over both seasons in both cultivars.

Conclusion

These results indicate that plant density has an indirect effect on milling quality by influencing TGW, which affected total protein content, and thus, HRY and the response differ between cultivars. Furthermore, this study demonstrated that within a population of 18 to 231 plants/m2 at establishment, the physicochemical and cooking parameters are not affected by sowing rate.

Significance and novelty

This study is the first to analyze the grain physicochemical and cooking quality parameters at densities above 100 plants/m2 and evaluate the effect of sowing rate on the grain quality of differing grain types within Australia. Comparisons between the low (50–70 kg/ha) and standard sowing rate (130–150 kg/ha) revealed no difference in HRY, and these results are important to farmers and demonstrate a reduction in plant density due to poor establishment, environmental or bird damage does not affect crop yield or grain quality and thus their economic return.
Uncommon finding of a “black node” in a patient with malignant melanoma and arthroplasty: A case report
Authors: Hansen Torsten , Keiler Andreas , Brochhausen Christoph , Schulz Birte , Stege Helger
Published: September 2020

Postarthroplasty lymphadenopathy should be kept in mind particularly in patients with tumor (eg, melanoma) with a long‐term history of total joint replacement therapy. Microscopy is mandatory in establishing diagnosis and is thus helpful for therapy.
Processing and properties of SiC composites made via binder jet 3D printing and infiltration and pyrolysis of preceramic polymer
Authors: Cramer Corson L. , Armstrong Herb , Flores‐Betancourt Alexis , Han Lu , Elliott Amy M. , Lara‐Curzio Edgar , Saito Tomonori , Nawaz Kashif
Published: September 2020

The effect of polymer infiltration and pyrolysis (PIP) cycles with polycarbosiloxane on the microstructure, air leak rate, and properties of SiC composites manufactured by a combination of binder jet 3D printing and PIP is reported. The density, Young's modulus and flexural strength of disk‐shaped components increased with the number of PIP cycles. In the case of density, it increased from 2.05 g/cm3 in one PIP cycle to 2.33 g/cm3 after three PIP cycles, while values of flexural strength and Young's modulus at room temperature after three PIP cycles reached 66.8 ± 2.5 MPa and 69.5 ± 2.8 GPa, respectively. Conversely, the air leak rate was found to decrease with number of PIP cycles, and it reached a value of 4 mbar‐L/s after three cycles. The instantaneous coefficient of thermal expansion of the composite was found to change minimally with the number of PIP cycles and had a value of 4 ± 1.2 ppm/°C between 200°C and 1000°C. Thermal conductivity was found to increase with number of PIP cycles and to decrease with temperature. For example, after three PIP cycles it was found to change from 6.72 ± 0.08 to 6.98 ± 0.08 W/mK at 25°C and 7.36 ± 0.08 to 7.96 ± 0.08 W/mK at 300°C. These values were lower than those of crystalline SiC because of the amorphous nature of the matrix and the presence of pores and cracks.
Antennal‐lobe neurons in the moth Helicoverpa armigera: Morphological features of projection neurons, local interneurons, and centrifugal neurons
Authors: Kymre Jonas Hansen , Berge Christoffer Nerland , Chu Xi , Ian Elena , Berg Bente G.
Published: September 2020

The relatively large primary olfactory center of the insect brain, the antennal lobe (AL), contains several heterogeneous neuronal types. These include projection neurons (PNs), providing olfactory information to higher‐order neuropils via parallel pathways, and local interneurons (LNs), which provide lateral processing within the AL. In addition, various types of centrifugal neurons (CNs) offer top‐down modulation onto the other AL neurons. By performing iontophoretic intracellular staining, we collected a large number of AL neurons in the moth, Helicoverpa armigera, to examine the distinct morphological features of PNs, LNs, and CNs. We characterize 190 AL neurons. These were allocated to 25 distinct neuronal types or sub‐types, which were reconstructed and placed into a reference brain. In addition to six PN types comprising 15 sub‐types, three LN and seven CN types were identified. High‐resolution confocal images allowed us to analyze AL innervations of the various reported neurons, which demonstrated that all PNs innervating ventroposterior glomeruli contact a protocerebral neuropil rarely targeted by other PNs, that is the posteriorlateral protocerebrum. We also discuss the functional roles of the distinct CNs, which included several previously uncharacterized types, likely involved in computations spanning from multisensory processing to olfactory feedback signalization into the AL.
Transparent many‐core partitioning for high‐performance big data I/O
Authors: Lee Chan‐Gyu , Cho Joong‐Yeon , Kim Jooho , Jin Hyun‐Wook
Published: September 2020

As the number of cores equipped in a single computing node is rapidly increasing, utilizing many cores for contemporary applications in an efficient manner is a challenging issue. We need to consider both parallelization and locality to fully exploit many cores for multifarious operations of emerging applications. In particular, big data applications perform computation and I/O intensive operations alternately. For instance, Apache Hadoop MapReduce assumes local persistent storage for each computing node. Thus, unlike traditional parallel programming models, the MapReduce framework performs not only networking but also storage I/O. In this study, we aim to improve the locality of network and storage I/O operations on many‐core systems by partitioning cores for I/O system calls and event handlers. In order to implement fine‐grained many‐core partitioning, we decouple the system call context from the user‐level process by suggesting message‐based system calls. The suggested design provides user‐level transparency and does not require any kernel‐level modifications. In addition, we propose a scheme that dynamically decides the core affinity of system calls and event handlers by considering locality, run‐time loads, and hardware architectures. The experimental results show that the proposed many‐core partitioning can improve the locality of network and storage I/O operations in an integrated manner for MapReduce applications.
Elimination profiles of betamethasone after different administration routes: Evaluation of the reporting level and washout periods to ensure safe therapeutic administrations
Authors: Coll Sergi , Monfort Núria , Alechaga Élida , Matabosch Xavier , Pérez‐Mañá Clara , Ventura Rosa
Published: September 2020

Betamethasone (BET) is prohibited in sports competitions when administered by systemic routes, and it is allowed by other routes for therapeutic purposes. In out‐of‐competition periods, there is no restriction of use. The present work aimed to assess the urinary excretion of BET and its metabolites after allowed and prohibited administrations to verify the suitability of the current reporting level of 30 ng/ml used to distinguish allowed and prohibited administrations and to establish washout periods for oral and intramuscular (IM) administrations when out‐of‐competition treatments are needed. BET was administered to healthy volunteers by different routes: topical (10 mg/day for 5 days, n = 6 males), intranasal (320 μg/day for 3 days, n = 4 males and 4 females), oral (0.5 mg, n = 8 males) or IM (6 mg, n = 6 males, or 12 mg, n = 4 males and 4 females). Urine and plasma samples collected before and after administration were analysed using liquid chromatography–tandem mass spectrometry. Among all studied metabolites, the parent drug was selected as the best discriminatory marker. After topical administration, BET concentrations were lower than 6.6 ng/ml. However, after intranasal treatment, some samples at concentrations close to or higher than 30 ng/ml were detected, suggesting the need to revise the current reporting level. Urinary concentrations after oral and intranasal administrations were similar, and after IM administration, concentrations were much higher. Taking into account all information, a urinary reporting level of 60 ng/ml is proposed. Washout periods of at least 48 and 96 h are recommended after oral and IM administrations, respectively.
Relative contribution of risk factors/co‐morbidities to heart failure pathogenesis: interaction with ejection fraction
Authors: Giamouzis Grigorios , Xanthopoulos Andrew , Papamichalis Michail , Chroub‐Papavaiou Artemis‐Nantia , Pantziou Aikaterini , Simou Anthi , Dimos Apostolos , Bourazana Angeliki , Skoularigis John , Triposkiadis Filippos
Published: September 2020

Aims

The relative impact of each individual coexisting morbidity on the pathogenesis of heart failure (HF) is incompletely understood. This study aimed to evaluate the prevalence of individual cardiac and non‐cardiac coexisting morbidities both in the overall HF population and in the subgroup of HF patients with a single coexisting morbidity, stratified by left ventricular ejection fraction (LVEF) categories, as a measure of the relative contribution of each co‐morbidity to the pathogenesis of HF.

Methods and results

This is a prospective, observational study, in which unselected ambulatory patients with chronic HF visiting the HF clinic of a tertiary university hospital from January 2016 to January 2019 were classified according to baseline LVEF into three groups: (i) LVEF < 40%, (ii) LVEF = 40–49%, and (iii) LVEF ≥ 50% and then evaluated for various coexisting morbidities. Overall, 1064 patients (age 73.4 ± 12.1 years, male gender 57.7%, LVEF 43.6 ± 13.9, N‐terminal pro‐brain natriuretic peptide 2187 ± 710 ng/L, and estimated glomerular filtration rate 67.2 ± 25 mL/min/1.73 m2) were recruited in this study. Of these, 361 (33.9%) had an LVEF < 40%, 247 (23.2%) an LVEF = 40–49%, and 456 (42.9%) an LVEF ≥ 50%. There were 90 (8.5%) HF patients with a single coexisting morbidity, 33 (36.7%) with LVEF ≥ 50%, 27 (30.0%) with LVEF = 40–49%, and 30 (33.3%) with LVEF < 40%. Among these patients, those with LVEF ≥ 50% suffered mostly from hypertension (85.7%), whereas the second most common coexisting morbidity was atrial fibrillation (AF) (9.5%). HF patients with LVEF = 40–49% usually suffered from hypertension (35.7%), AF (28.6%), or myocardial infarction (MI) (21.4%). Finally, HF patients with LVEF < 40% usually suffered from MI (30.8%), AF (30.8%), or hypertension (15.4%).

Conclusions

Hypertension is strongly associated with the development of HF with low, intermediate, or near‐normal/normal LVEF whereas a history of MI or AF with HF with a low or an intermediate LVEF.
Design of a Sensitive Electrochemical Sensor Based on Ferrocene‐reduced Graphene Oxide/Mn‐spinel for Hydrazine Detection
Authors: Singh Manorama , Bhardiya Smita R. , Asati Ambika , Sheshma Harendra , Rai Ankita , Rai Vijai K.
Published: September 2020

Herein, we report construction of a ferrocene‐reduced graphene oxide‐Mn spinel modified glassy carbon electrode (Fc−G/Mn3O4/GCE) as a sensitive electrochemical probe for hydrazine detection via its oxidation. The synergistic effect of ferrocene, graphene oxide and Mn3O4 provides it a great electrocatalytic effect. The electrochemical investigations of Fc−G/Mn3O4/GCE were studied using cyclic voltammetry, while differential pulse voltammetry was utilized for recording the electrocatalytic sensing of hydrazine. The prepared Fc−G/Mn3O4 offers a platform for sensitive and selective detection of low‐level hydrazine in two linear ranges from 0.045 to 108 μM and 108 to 653 μM with limit of detection 8.5 nM. Real sample analysis was also performed in local industrial water samples with satisfactory recovery results.
A performance analysis of prediction intervals for count time series
Authors: Homburg Annika , Weiß Christian H. , Alwan Layth C. , Frahm Gabriel , Göb Rainer
Published: September 2020

One of the major motivations for the analysis and modeling of time series data is the forecasting of future outcomes. The use of interval forecasts instead of point forecasts allows us to incorporate the apparent forecast uncertainty. When forecasting count time series, one also has to account for the discreteness of the range, which is done by using coherent prediction intervals (PIs) relying on a count model. We provide a comprehensive performance analysis of coherent PIs for diverse types of count processes. We also compare them to approximate PIs that are computed based on a Gaussian approximation. Our analyses rely on an extensive simulation study. It turns out that the Gaussian approximations do considerably worse than the coherent PIs. Furthermore, special characteristics such as overdispersion, zero inflation, or trend clearly affect the PIs' performance. We conclude by presenting two empirical applications of PIs for count time series: the demand for blood bags in a hospital and the number of company liquidations in Germany.
A real‐world comparison of cisplatin vs cetuximab used concurrently with radiation in the treatment of locally advanced oropharyngeal carcinoma
Authors: Fung Andrea S. , Afzal Arfan Raheen , Banerjee Robyn , Debenham Brock , Hao Desiree
Published: September 2020

Background

This population‐based retrospective study compares the efficacy of cisplatin (cis‐RT) vs cetuximab (cetux‐RT) with concurrent radiation as definitive treatment in patients with oropharyngeal carcinoma (OPC).

Methods

Patients with OPC treated in Alberta with cis‐RT or cetux‐RT between 2006 and 2016 were evaluated. Median disease‐free survival (DFS) and overall survival (OS) were assessed using the Kaplan‐Meier method. Multivariable analysis (MVA) was completed with a Cox proportional hazards model.

Results

Among 546 patients with OPC, 431 (78.9%) received cis‐RT and 115 (21.1%) cetux‐RT. Patients treated with cetux‐RT were more likely to develop a recurrence after treatment compared to cis‐RT (25% vs 15%, P = .01). On MVA, current smoking, human papillomavirus (HPV)‐negative status, higher Charlson comorbidity index (CCI), T‐stage, and cetux‐RT predicted for worse DFS and OS. Outcomes in older patients with a higher CCI still favored cis‐RT.

Conclusions

Our data reaffirm results from randomized studies showing better survival outcomes with cis‐RT compared to cetux‐RT even among those who are >65 with CCI ≥3.
Postremission therapy with repeated courses of high‐dose cytarabine, idarubicin, and limited autologous stem cell support achieves a very good long‐term outcome in European leukemia net favorable and intermediate‐risk acute myeloid leukemia
Authors: Borlenghi Erika , Cattaneo Chiara , Cerqui Elisa , Archetti Silvana , Bertoli Diego , Bellotti Daniela , Gramegna Doriana , Soverini Giulia , Oberti Margherita , Schieppati Francesca , Pagani Chiara , Passi Angela , Sciumé Margherita , Farina Mirko , Carbone Cecilia , Crippa Claudia , Dalceggio Daniela , Tucci Alessandra , Rossi Giuseppe
Published: September 2020

Consolidation treatment in acute myeloid leukemia (AML) patients achieving complete remission (CR) is warranted. High‐dose cytarabine (HDAC) is considered first choice in favorable risk and an option in intermediate‐risk AML. However, its optimal dose and schedule, as well as the benefit of additional chemotherapy agents remain controversial. Herein, we report on the long‐term outcome of consecutive unselected AML patients treated with repeated courses of HDAC, with the addition of idarubicin, followed by autologous peripheral blood stem cell (PBSC) support, in order to limit toxicity, according to Northern Italy Leukemia Group (NILG) AML‐01/00 study (EUDRACT number 00400673). Among 338 patients consecutively diagnosed from 2001 to 2017 at our center, 148 with high‐risk AML (adverse cytogenetic, isolated FLT3‐internal tandem duplication mutation, refractory to first induction) were addressed to allogeneic stem cell transplant. All other cases, 186 patients (55%), median age 53 (range 19–75), were considered standard‐risk and received the NILG AML‐01/00 program. After achieving CR, patients were mobilized with cytarabine 8 g/sqm to collect autologous CD34+‐PBSC and received three consolidation cycles with HDAC (20 g/sqm) plus idarubicin (20 mg/sqm) per cycle, followed by reinfusion of limited doses of CD34+ PBSC (1‐2x106/kg). The program was completed by 160 (86%) patients. Toxicity was acceptable. Neutrophils recovered a median of 10 days. Treatment‐related mortality was 3/160 (1.8%). After a median follow‐up of 66.4 months, overall survival (OS) and relapse‐free survival (RFS) at 5‐years were 61.4% and 52.4%, respectively. Twenty‐eight selected patients aged >65 had similar outcomes. According to European leukemia net‐2010 classification, the OS and RFS at 5‐years were 76.4% and 65% in favorable risk, without differences between molecular subgroups, 52.3% and 47.2% in Intermediate‐I, 45.2% and 36.5% in Intermediate‐II risk patients, respectively. In conclusion, consolidation including repeated courses of high dose cytarabine and idarubicin, with limited PBSC support, proved feasible and very effective in nonhigh risk patients. The incorporation of novel agents in its backbone may be tested to further improve patient's prognosis.
The relationship of health literacy, wellbeing and religious beliefs in neglected and unequal contexts—Results of a survey study in central Afghanistan
Authors: Harsch Stefanie , Jawid Asadullah , Jawid M Ebrahim , Saboga Nunes Luis , Sahrai Diana , Bittlingmayer Uwe H.
Published: September 2020

Issue addressed

While multiple studies worldwide reveal the strong impact of various determinants on health literacy, empirical data on the link between health literacy and other important dimensions of health equity (such as quality of life, beliefs and health literacy in crisis‐affected religious countries such as Afghanistan) is scarce. To inform and develop promising health promotion for people in need, we analysed the relationship between health literacy, quality of life and spiritual and religious beliefs.

Methods

In this first study on health literacy in Afghanistan, we interviewed 522 men and 324 women in the Ghazni province. Besides the HLS‐EU‐16, we used Quality of Life (WHO‐QoL‐BREF) and the WHO‐SRPB‐BREF questionnaires in Dari and Pashto. We performed descriptive, uni‐ and multivariate analyses.

Results

The levels of HL, QoL and SRPB_coping are comparatively low among Afghan men from the Ghazni province, but higher among women on all scales. HL and QoL are positively associated with education and negatively with age (in the female subsample). HL and QoL show a moderate correlation among women but not among men. We found mixed results for the relationship between SRPB and HL or QoL.

Conclusions

The study highlights that health literacy is not a singular factor but related to wellbeing.

So What?

Health education might be promising while combining health literacy to the idea of quality of life of everyone, even those living in poor and illiterate environments.
Integrating Exposure and Effect Distributions with the Ecotoxicity Risk Calculator: Case Studies with Crop Protection Products
Authors: Dreier David A , Rodney Sara I , Moore Dwayne RJ , Grant Shanique L , Chen Wenlin , Valenti Theodore W , Brain Richard A
Published: September 2020

Risk curves describe the relationship between cumulative probability and magnitude of effect and thus express far more information than risk quotients. However, their adoption has remained limited in ecological risk assessment. Therefore, we developed the Ecotoxicity Risk Calculator (ERC) to simplify the derivation of risk curves, which can be used to inform risk management decisions. Case studies are presented with crop protection products, highlighting the utility of the ERC at incorporating various data sources, including surface water modeling estimates, monitoring observations, and species sensitivity distributions. Integr Environ Assess Manag 2021;17:321–330. © 2020 Syngenta Crop Protection, LLC. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)

KEY POINTS

Risk curves describe the relationship between distributions of exposure and effect. The Ecotoxicity Risk Calculator can be used to generate risk curves from various data sources. Case studies are presented with risk curves for crop protection products.
Integrating proteomics into precision oncology
Authors: Wahjudi Leonie W. , Bernhardt Stephan , Abnaof Khalid , Horak Peter , Kreutzfeldt Simon , Heining Christoph , Borgoni Simone , Becki Corinna , Berg Daniela , Richter Daniela , Hutter Barbara , Uhrig Sebastian , Pfütze Katrin , Leichsenring Jonas , Glimm Hanno , Brors Benedikt , von Kalle Christof , Stenzinger Albrecht , Korf Ulrike , Fröhling Stefan , Wiemann Stefan
Published: September 2020

DNA sequencing and RNA sequencing are increasingly applied in precision oncology, where molecular tumor boards evaluate the actionability of genetic events in individual tumors to guide targeted treatment. To work toward an additional level of patient characterization, we assessed the abundance and activity of 27 proteins in 134 patients whose tumors had previously undergone whole‐exome and RNA sequencing within the Molecularly Aided Stratification for Tumor Eradication Research (MASTER) program of National Center for Tumor Diseases, Heidelberg. Proteomic and phosphoproteomic targets were selected to reflect the most relevant therapeutic baskets in MASTER. Among six different therapeutic baskets, the proteomic data supported treatment recommendations that were based on DNA and RNA analyses in 10% to 57% and frequently suggested alternative treatment options. In several cases, protein activities explained the patients' clinical course and provided potential explanations for treatment failure. Our study indicates that the integrative analysis of DNA, RNA and protein data may refine therapeutic stratification of individual patients and, thus, holds potential to increase the success rate of precision cancer therapy. Prospective validation studies are needed to advance the integration of proteomic analysis into precision oncology.
Predictors of mammographic microcalcifications
Authors: Azam Shadi , Eriksson Mikael , Sjölander Arvid , Gabrielson Marike , Hellgren Roxanna , Czene Kamila , Hall Per
Published: September 2020

We examined the association between established risk factors for breast cancer and microcalcification clusters and their asymmetry. A cohort study of 53 273 Swedish women aged 30 to 80 years, with comprehensive information on breast cancer risk factors and mammograms, was conducted. Total number of microcalcification clusters and the average mammographic density area were measured using a Computer Aided Detection system and the STRATUS method, respectively. A polygenic risk score for breast cancer, including 313 single nucleotide polymorphisms, was calculated for those women genotyped (N = 7387). Odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for potential confounders, were estimated. Age was strongly associated with microcalcification clusters. Both high mammographic density (>40 cm2), and high polygenic risk score (80‐100 percentile) were associated with microcalcification clusters, OR = 2.08 (95% CI = 1.93‐2.25) and OR = 1.22 (95% CI = 1.06‐1.48), respectively. Among reproductive risk factors, life‐time breastfeeding duration >1 year was associated with microcalcification clusters OR = 1.22 (95% CI = 1.03‐1.46). The association was confined to postmenopausal women. Among lifestyle risk factors, women with a body mass index ≥30 kg/m2 had the lowest risk of microcalcification clusters OR = 0.79 (95% CI = 0.73‐0.85) and the association was stronger among premenopausal women. Our results suggest that age, mammographic density, genetic predictors of breast cancer, having more than two children, longer duration of breast‐feeding are significantly associated with increased risk of microcalcification clusters. However, most lifestyle risk factors for breast cancer seem to protect against presence of microcalcification clusters. More research is needed to study biological mechanisms behind microcalcifications formation.
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

The 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

Mitotic 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

Early 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

Skin 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

Aims

This analysis identifies the correlates of 60‐ and 120‐day telephone‐based study follow‐ups among community‐dwelling adults in North Central Florida.

Methods

Six 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.

Results

Physical 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.

Conclusions

Health 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

Natalizumab 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

Background

Hypertension 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 Methods

We 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.

Results

There 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.

Conclusions

Echocardiography 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

Background

Studies 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.

Methods

This 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.

Results

The 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.

Conclusions

Our 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

Background/Purpose

No 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.

Methods

In 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.

Results

Between 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%.

Conclusions

Oral 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

Introduction

Up 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).

Methods

Participants 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.

Results

Of 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.

Conclusions

Despite 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

Introduction

The 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.

Methods

In 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.

Results

Between 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.

Conclusions

The 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 Evidence

5

Technical Efficacy Stage

3