bluuebunny/crossref_metadata_2025 huggingface dataset:
Spermatozoa morphology changes during reproduction and first observation of acrosomal contact in two dioecious species of Macrobiotidae (Tardigrada: Eutardigrada)
Authors: Sugiura Kenta , Matsumoto Midori
Published: September 2020

Mating behaviours for two species of dioecious eutardigrades: a strain of Paramacrobiotus sp. and Macrobiotus shonaicus (Stec et al., 2018) have been recorded previously, and observations have indicated that spermatozoa of both species are first released into the environment, then swim through the cloaca of the females and into the spermatheca. The fusion of gamete nuclei has not yet occurred in a laid egg. Therefore, it has been suggested that fertilization is completed externally as the egg is released into the environment before the nuclei of the gametes fuse. In the present study, the spermatozoa of both Paramacrobiotus sp. and M. shonaicus spermatozoa underwent morphological changes during reproduction. In morphometrical analyses of testicular spermatozoa, the tail, mid-piece, nucleus, and acrosome were significantly longer in Paramacrobiotus sp. compared with M. shonaicus. The nuclei of both the testicular and spermathecal spermatozoa were equally coiled, but the latter had shorter tails in both species. These spermatozoa were present on the surface of the egg chorion after oviposition. The tip of the acrosomes lay buried in the chorion, suggesting that penetration had occurred. We also proposed that the reduced tail is a conserved trait, at least in Macrobiotidae.
Cardiac events in Patients in their forties with Kawasaki disease and regression of coronary artery aneurysms
Authors: Tsuda Etsuko , Yoneda Shuichi , Asaumi Yasuhide , Suzuki Atsuko
Published: September 2020

Over a 50-year period from the first description of Kawasaki disease, we encountered three male patients with a history of Kawasaki disease, who had their first cardiac events in their forties. They were considered to have almost normal coronary arteries in the coronary angiograms when they were children and adolescents. They had no follow-up examinations after 20 years old. The 1st patient had an acute myocardial infarction, and the 2nd was a new appearance of coronary aneurysm and stenotic lesions with coronary artery calcification. The 3rd patient had unexpected sudden death. The interval from the onset of Kawasaki disease to the cardiac events ranged from 37 to 38 years. In the former two patients, coronary artery lesions could not be evaluated immediately after Kawasaki disease. Although the 3rd patient had bilateral medium-sized coronary artery aneurysms, his coronary aneurysms regressed 1 year after acute Kawasaki disease. The intimal thickening at a previous coronary aneurysm at the age of 19 was mild. The patients with regressed coronary aneurysms were asymptomatic for about 40 years after Kawasaki disease, prior to their cardiac events. Coronary artery calcification of the proximal portion of the major coronary arteries was a predictable marker in such patients. To prevent serious cardiac events in middle-aged adult patients, reevaluation of coronary artery lesions and restarting of anti-thrombotic therapy are needed. We must be aware that there are some differences in the clinical course and time of cardiac events between patients with giant aneurysms and those with medium aneurysms.
Sentence repetition with bilinguals with and without DLD: Differential effects of memory, vocabulary, and exposure
Authors: Pratt Amy S. , Peña Elizabeth D. , Bedore Lisa M.
Published: September 2020

Though previous research has shown that sentence repetition (SR) is an informative tool for identifying developmental language disorder (DLD) in bilinguals, little is understood about the skills that underlie children's performance on the task. With a population of 136 school-age Spanish–English bilinguals, the present study explores the contribution of verbal short-term memory, vocabulary, and language exposure on two SR tasks developed in English and Spanish. Results indicate that these skills may differentially underlie SR in typical versus disordered populations. Whereas the strongest predictors of English SR performance for typical bilingual children were expressive vocabulary and language exposure, bilingual children with DLD relied most heavily on verbal short-term memory. ROC curves to determine the classification accuracy of SR were conducted. Classification accuracy was excellent, with area under the curve reaching .92 for the English SR task and .87 for Spanish SR.
Post IORT seroma complication in breast cancer surgery
Authors: Abdel Hadi Maha , Al-Muhanna Afnan , Abu Arida Lina , Lutfi Dina
Published: September 2020

Background:

Intraoperative radiotherapy (IORT) has gained popularity over recent years due to its impact on shortening the radiotherapy treatment time for early breast cancer. It has certainly proven effective as an exclusive treatment or when combined with whole breast irradiation (WBIR). Seroma is a common non-life-threatening complication that may delay treatment and impose challenges on radiological diagnostic follow-up.

Aim:

To review and compare the occurrence of seroma in patients who received exclusive IORT or when combined with WBIR and to outline the diagnostic challenges encountered during radiological follow-up.

Materials and methods:

Based on strict selection criteria, all eligible patients who received IORT ± WBIR treatment between 2012 and 2019 in a university hospital setting were included. Demographic data, histological diagnosis, tumour size, tumour grade, lymphovascular invasion, nodal status, receptor status, treatment with neoadjuvant hormonal chemotherapy, applicator size, dose used, duration of radiotherapy treatment, timing of seroma development and duration of seroma were documented. Both clinical and radiological follow-up were exercised in all patients.

Results:

The total number of patients treated with breast conserving surgery (BCS) and IORT was 86. Age ranged between 31 and 75 years with the median age of 51 years. Patients treated exclusively with IORT were 39 (45%) while those who received the IORT as a boost were 47 (55%). Seroma was observed in 39(45%) of both IORT and IORT\WBIR patients. Those included 15(38%) of the exclusive IORT treated patients and 24 (62%) of those treated as a boost. Duration of asymptomatic seroma ranged from 6 months to 6 years. Repeated aspiration was performed in 2 (5%) patients. Postoperative seroma occurred independent of age histological diagnosis, tumour size, tumour grade, lymphovascular invasion, nodal status, receptor status, treatment with neoadjuvant hormonal\chemotherapy, applicator size, dose used or duration of radiotherapy treatment. All reviewed patients have shown increased risk of developing seroma; however, an increased incidence of seroma in the IORT + WBIR treated patients was higher than those who received exclusive IORT treatment.

Conclusion:

Postoperative seroma is a common non-life-threatening entity that occasionally may lead to delay in the subsequent treatment plan. IORT is a safe modality with many benefits; however, it may increase the risk of seroma formation independent of the clinical parameters. Promoting the expertise in post IORT breast imaging aids in overcoming diagnostic challenges.
Mortality forecasting using a Lexis-based state-space model
Authors: Andersson Patrik , Lindholm Mathias
Published: September 2020

A new method of forecasting mortality is introduced. The method is based on the continuous-time dynamics of the Lexis diagram, which given weak assumptions implies that the death count data are Poisson distributed. The underlying mortality rates are modelled with a hidden Markov model (HMM) which enables a fully likelihood-based inference. Likelihood inference is done by particle filter methods, which avoids approximating assumptions and also suggests natural model validation measures. The proposed model class contains as special cases many previous models with the important difference that the HMM methods make it possible to estimate the model efficiently. Another difference is that the population and latent variable variability can be explicitly modelled and estimated. Numerical examples show that the model performs well and that inefficient estimation methods can severely affect forecasts.
A community-based intervention to prevent serious complications and death 2 years after discharge in people with spinal cord injury in Bangladesh (CIVIC): a randomised trial
Authors: Hossain Mohammad Sohrab , Harvey Lisa A. , Islam Md. Shofiqul , Rahman Md. Akhlasur , Muldoon Stephen , Biering-Sorensen Fin , Jan Stephen , Liu Hueiming , Li Qiang , Cameron Ian D. , Taylor Valerie , Lindley Richard I. , Billot Laurent , Herbert Robert D.
Published: September 2020

Study design

Randomised controlled trial.

Objectives

To determine the effectiveness of a sustainable community-based intervention designed to prevent serious complications and death 2 years after discharge in people with spinal cord injury in Bangladesh.

Setting

Bangladesh.

Methods

A pragmatic randomised controlled trial was undertaken. People who had sustained a spinal cord injury in the preceding 2 years, were wheelchair-dependent, and were about to be discharged from hospital in Bangladesh were recruited and randomised to an Intervention or Control group using a concealed allocation procedure stratified by level of lesion (tetraplegia/paraplegia). Participants in the Intervention group received 36 phone calls and three home visits over the first 2 years following discharge. All participants received usual post-discharge care. Survival status and date of death were determined by blinded assessors 2 years after randomisation.

Results

Between July 2015 and March 2018, 410 participants were randomised (204 to Intervention, 206 to Control). There was no loss to follow up. At 2 years, 15 (7.4%) participants in the Intervention group and 16 (7.8%) participants in the Control group had died (hazard ratio from unadjusted Cox model = 0.93 [95% CI, 0.46 to 1.89]; p from log rank test 0.85). There were no clinically important or statistically significant average causal effects of intervention on the incidence or severity of complications.

Conclusion

A program of community-based care for people with recent spinal cord injury in Bangladesh involving frequent phone contact and occasional in-person contact with a health professional after discharge from hospital is no better at preventing death at 2 years than usual care.
Reduction in MLKL-mediated endosomal trafficking enhances the TRAIL-DR4/5 signal to increase cancer cell death
Authors: Park Se-Yeon , Park Han-Hee , Park Sang-Yeong , Hong Sun Mi , Yoon Seongmin , Morgan Michael J. , Kim You-Sun
Published: September 2020

Mixed lineage kinase domain-like (MLKL) is an essential molecule of necroptosis, a cell death process that is initiated by direct disruption of the plasma membrane. During necroptosis, MLKL is phosphorylated by receptor interacting protein kinase-3 (RIPK3 or RIP3), and then translocates to the plasma membrane to disrupt membrane integrity. Recent data suggest that MLKL also has a RIP3-indendent function in the generation of intraluminal and extracellular vesicles (EVs), as well as in myelin sheath breakdown when promoting sciatic nerve regeneration. Here we show that depletion of MLKL enhances TRAIL-induced cell death in a RIP3-independent manner. Depletion of MLKL leads to prolonged cytotoxic signals that increase TRAIL-induced cell death. Initially, TRAIL binds to DR5 at the cell surface and is endocytosed at similar rates in MLKL-expressing and MLKL-depleted cells, eventual degradation of intracellular TRAIL by the lysosome is delayed in MLKL-depleted cells, corresponding with prolonged/enhanced intracellular signals such as p-ERK and p-p38 in these cells. Colocalization of TRAIL with the marker of early endosomes, EEA1 suggests that TRAIL is accumulated in early endosomes in MLKL-depleted cells compared to MLKL-expressing cells. This indicates that depletion of MLKL reduces receptor-ligand endosomal trafficking leading to increased TRAIL-cytotoxicity. An MLKL mutant that compromises its necroptotic function and its function in the generation of EVs was sufficient to rescue MLKL deficiency, suggesting that the N-terminal structural elements necessary for these functions are not required for the function of MLKL in the intracellular trafficking associated with regulating death receptor cytotoxicity. A reduction in MLKL expression in cancer cells would therefore be expected to result in enhanced TRAIL-induced therapeutic efficacy.
Distinct superconducting properties and hydrostatic pressure effects in 2D α- and β-Mo2C crystal sheets
Authors: Fan Yunjie , Xu Chuan , Liu Xiang , Ma Chao , Yin Yuewei , Cheng Hui-Ming , Ren Wencai , Li Xiaoguang
Published: September 2020

Recently, 2D Mo2C, a new member of the MXene family, has attracted much attention due to the exotic superconducting properties discovered in 2D α-Mo2C. Here, not only 2D α-Mo2C but also 2D β-Mo2C crystal sheets with distinct disordered carbon distributions were successfully grown. 2D β-Mo2C shows a much stronger superconductivity than 2D α-Mo2C, and their superconductivities have different hydrostatic pressure responses. The superconducting transition temperature Tc of 2D α-Mo2C shows a dome-shaped profile under pressure, implying the existence of two competing effects arising from phononic and electronic properties, while for 2D β-Mo2C, Tc decreases monotonically with increasing pressure, possibly due to phonon stiffening. These results indicate that the electronic properties have a more important influence on the superconductivity in 2D α-Mo2C compared to 2D β-Mo2C. The ordered and disordered carbon distributions in 2D α-Mo2C and β-Mo2C, respectively, may be the underlying origin for their different electronic and superconducting properties.
Ecosystem-based fisheries management forestalls climate-driven collapse
Authors: Holsman K. K. , Haynie A. C. , Hollowed A. B. , Reum J. C. P. , Aydin K. , Hermann A. J. , Cheng W. , Faig A. , Ianelli J. N. , Kearney K. A. , Punt A. E.
Published: September 2020

Climate change is impacting fisheries worldwide with uncertain outcomes for food and nutritional security. Using management strategy evaluations for key US fisheries in the eastern Bering Sea we find that Ecosystem Based Fisheries Management (EBFM) measures forestall future declines under climate change over non-EBFM approaches. Yet, benefits are species-specific and decrease markedly after 2050. Under high-baseline carbon emission scenarios (RCP 8.5), end-of-century (2075–2100) pollock and Pacific cod fisheries collapse in >70% and >35% of all simulations, respectively. Our analysis suggests that 2.1–2.3 °C (modeled summer bottom temperature) is a tipping point of rapid decline in gadid biomass and catch. Multiyear stanzas above 2.1 °C become commonplace in projections from ~2030 onward, with higher agreement under RCP 8.5 than simulations with moderate carbon mitigation (i.e., RCP 4.5). We find that EBFM ameliorates climate change impacts on fisheries in the near-term, but long-term EBFM benefits are limited by the magnitude of anticipated change.
Spatial validation reveals poor predictive performance of large-scale ecological mapping models
Authors: Ploton Pierre , Mortier Frédéric , Réjou-Méchain Maxime , Barbier Nicolas , Picard Nicolas , Rossi Vivien , Dormann Carsten , Cornu Guillaume , Viennois Gaëlle , Bayol Nicolas , Lyapustin Alexei , Gourlet-Fleury Sylvie , Pélissier Raphaël
Published: September 2020

Mapping aboveground forest biomass is central for assessing the global carbon balance. However, current large-scale maps show strong disparities, despite good validation statistics of their underlying models. Here, we attribute this contradiction to a flaw in the validation methods, which ignore spatial autocorrelation (SAC) in data, leading to overoptimistic assessment of model predictive power. To illustrate this issue, we reproduce the approach of large-scale mapping studies using a massive forest inventory dataset of 11.8 million trees in central Africa to train and validate a random forest model based on multispectral and environmental variables. A standard nonspatial validation method suggests that the model predicts more than half of the forest biomass variation, while spatial validation methods accounting for SAC reveal quasi-null predictive power. This study underscores how a common practice in big data mapping studies shows an apparent high predictive power, even when predictors have poor relationships with the ecological variable of interest, thus possibly leading to erroneous maps and interpretations.
Global phosphorus shortage will be aggravated by soil erosion
Authors: Alewell Christine , Ringeval Bruno , Ballabio Cristiano , Robinson David A. , Panagos Panos , Borrelli Pasquale
Published: September 2020

Soil phosphorus (P) loss from agricultural systems will limit food and feed production in the future. Here, we combine spatially distributed global soil erosion estimates (only considering sheet and rill erosion by water) with spatially distributed global P content for cropland soils to assess global soil P loss. The world’s soils are currently being depleted in P in spite of high chemical fertilizer input. Africa (not being able to afford the high costs of chemical fertilizer) as well as South America (due to non-efficient organic P management) and Eastern Europe (for a combination of the two previous reasons) have the highest P depletion rates. In a future world, with an assumed absolute shortage of mineral P fertilizer, agricultural soils worldwide will be depleted by between 4–19 kg ha−1 yr−1, with average losses of P due to erosion by water contributing over 50% of total P losses.
Spatial expression analyses of the putative oncogene ciRS-7 in cancer reshape the microRNA sponge theory
Authors: Kristensen Lasse S. , Ebbesen Karoline K. , Sokol Martin , Jakobsen Theresa , Korsgaard Ulrik , Eriksen Ann C. , Hansen Thomas B. , Kjems Jørgen , Hager Henrik
Published: September 2020

Circular RNAs (circRNAs) have recently gained substantial attention in the cancer research field where most, including the putative oncogene ciRS-7 (CDR1as), have been proposed to function as competitive endogenous RNAs (ceRNAs) by sponging specific microRNAs. Here, we report the first spatially resolved cellular expression patterns of ciRS-7 in colon cancer and show that ciRS-7 is completely absent in the cancer cells, but highly expressed in stromal cells within the tumor microenvironment. Additionally, our data suggest that this generally apply to classical oncogene-driven adenocarcinomas, but not to other cancers, including malignant melanoma. Moreover, we find that correlations between circRNA and mRNA expression, which are commonly interpreted as evidence of a ceRNA function, can be explained by different cancer-to-stromal cell ratios among the studied tumor specimens. Together, these results have wide implications for future circRNA studies and highlight the importance of spatially resolving expression patterns of circRNAs proposed to function as ceRNAs.
Indirect regulation of HMGB1 release by gasdermin D
Authors: Volchuk Allen , Ye Anna , Chi Leon , Steinberg Benjamin E. , Goldenberg Neil M.
Published: September 2020

The protein high-mobility group box 1 (HMGB1) is released into the extracellular space in response to many inflammatory stimuli, where it is a potent signaling molecule. Although research has focused on downstream HMGB1 signaling, the means by which HMGB1 exits the cell is controversial. Here we demonstrate that HMGB1 is not released from bone marrow-derived macrophages (BMDM) after lipopolysaccharide (LPS) treatment. We also explore whether HMGB1 is released via the pore-forming protein gasdermin D after inflammasome activation, as is the case for IL-1β. HMGB1 is only released under conditions that cause cell lysis (pyroptosis). When pyroptosis is prevented, HMGB1 is not released, despite inflammasome activation and IL-1β secretion. During endotoxemia, gasdermin D knockout mice secrete HMGB1 normally, yet secretion of IL-1β is completely blocked. Together, these data demonstrate that in vitro HMGB1 release after inflammasome activation occurs after cellular rupture, which is probably inflammasome-independent in vivo.
Just ten percent of the global terrestrial protected area network is structurally connected via intact land
Authors: Ward Michelle , Saura Santiago , Williams Brooke , Ramírez-Delgado Juan Pablo , Arafeh-Dalmau Nur , Allan James R. , Venter Oscar , Dubois Grégoire , Watson James E. M.
Published: September 2020

Land free of direct anthropogenic disturbance is considered essential for achieving biodiversity conservation outcomes but is rapidly eroding. In response, many nations are increasing their protected area (PA) estates, but little consideration is given to the context of the surrounding landscape. This is despite the fact that structural connectivity between PAs is critical in a changing climate and mandated by international conservation targets. Using a high-resolution assessment of human pressure, we show that while ~40% of the terrestrial planet is intact, only 9.7% of Earth’s terrestrial protected network can be considered structurally connected. On average, 11% of each country or territory’s PA estate can be considered connected. As the global community commits to bolder action on abating biodiversity loss, placement of future PAs will be critical, as will an increased focus on landscape-scale habitat retention and restoration efforts to ensure those important areas set aside for conservation outcomes will remain (or become) connected.
Publisher Correction: Dynamics for El Niño-La Niña asymmetry constrain equatorial-Pacific warming pattern
Authors: Hayashi Michiya , Jin Fei-Fei , Stuecker Malte F.
Published: September 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Systematic analysis of gut microbiota in pregnant women and its correlations with individual heterogeneity
Authors: Yang Hongling , Guo Ruochun , Li Shaochuan , Liang Fang , Tian Cheng , Zhao Xueqin , Long Yan , Liu Fei , Jiang Min , Zhang Yu , Ma Jun , Peng Mengni , Zhang Siyi , Ye Weitao , Gan Qiangsheng , Zeng Fangling , Mao Shanliang , Liang Qihua , Ma Xiaodong , Han Mengru , Gao Fei , Yang Rentao , Zhang Cheng , Xiao Lulu , Qin Junjie , Li Shenghui , Zhu Chunyan
Published: September 2020

The woman’s gut microbiota during pregnancy may support nutrient acquisition, is associated with diseases, and has been linked to infant health. However, there is limited information on gut microbial characteristics and dependence in pregnant women. In this study, we provide a comprehensive overview of the gut microbial characteristics of 1479 pregnant women using 16S rRNA gene sequencing of fecal samples. We identify a core microbiota of pregnant women, which displays a similar overall structure to that of age-matched nonpregnant women. Our data show that the gestational age-associated variation in the gut microbiota, from the ninth week of gestation to antepartum, is relatively limited. Building upon rich metadata, we reveal a set of exogenous and intrinsic host factors that are highly correlated with the variation in gut microbial community composition and function. These microbiota covariates are concentrated in basic host properties (e.g., age and residency status) and blood clinical parameters, suggesting that individual heterogeneity is the major force shaping the gut microbiome during pregnancy. Moreover, we identify microbial and functional markers that are associated with age, pre-pregnancy body mass index, residency status, and pre-pregnancy and gestational diseases. The gut microbiota during pregnancy is also different between women with high or low gestational weight gain. Our study demonstrates the structure, gestational age-associated variation, and associations with host factors of the gut microbiota during pregnancy and strengthens the understanding of microbe–host interactions. The results from this study offer new materials and prospects for gut microbiome research in clinical and diagnostic fields.
Appropriate reference region selection of 18F-florbetaben and 18F-flutemetamol beta-amyloid PET expressed in Centiloid
Authors: Cho Soo Hyun , Choe Yeong Sim , Park Seongbeom , Kim Young Ju , Kim Hee Jin , Jang Hyemin , Kim Seung Joo , Kim Jun Pyo , Jung Young Hee , Kim Byeong C. , Na Duk L. , Moon Seung Hwan , Seo Sang Won
Published: September 2020

The Centiloid (CL) is a method for standardizing amyloid beta (Aβ) quantification through different ligands and methods. To find the most appropriate reference region to reduce the variance in the Aβ CL unit between 18F-florbetaben (FBB) and 18F-flutemetamol (FMM), we conducted head-to-head comparisons from 56 participants using the direct comparison of FBB-FMM CL (dcCL) method with four reference regions: cerebellar gray (CG), whole cerebellum (WC), WC with brainstem (WC + B), and pons. The FBB and FMM dcCL units were highly correlated in four reference regions: WC (R2 = 0.97), WC + B (R2 = 0.98), CG (R2 = 0.92), and pons (R2 = 0.98). WC showed the largest effect size in both FBB and FMM. Comparison of the variance of the dcCL values within the young control group showed that with FBB, WC + B had the smallest variance and with FMM, the WC had the smallest variance. Additionally, WC + B showed the smallest absolute difference between FBB and FMM, followed by the WC, pons, and CG. We found that it would be reasonable to use the WC or WC + B as the reference region when converting FBB and FMM SUVRs into dcCL, which can increase the accuracy of standardizing FBB and FMM PET results.
Spatial attention and representation of time intervals in childhood
Authors: Magnani Barbara , Musetti Alessandro , Frassinetti Francesca
Published: September 2020

Spatial attention and spatial representation of time are strictly linked in the human brain. In young adults, a leftward shift of spatial attention by prismatic adaptation (PA), is associated with an underestimation whereas a rightward shift is associated with an overestimation of time both for visual and auditory stimuli. These results suggest a supra-modal representation of time left-to-right oriented that is modulated by a bilateral attentional shift. However, there is evidence of unilateral, instead of bilateral, effects of PA on time in elderly adults suggesting an influence of age on these effects. Here we studied the effects of spatial attention on time representation focusing on childhood. Fifty-four children aged from 5 to 11 years-old performed a temporal bisection task with visual and auditory stimuli before and after PA inducing a leftward or a rightward attentional shift. Results showed that children underestimated time after a leftward attentional shift either for visual or auditory stimuli, whereas a rightward attentional shift had null effect on time. Our results are discussed as a partial maturation of the link between spatial attention and time representation in childhood, due to immaturity of interhemispheric interactions or of executive functions necessary for the attentional complete influence on time representation.
The efficacy of first-line tyrosine kinase inhibitors combined with co-medications in Asian patients with EGFR mutation non-small cell lung cancer
Authors: Su Vincent Yi-Fong , Yang Kuang-Yao , Huang Ting-Yu , Hsu Chia-Chen , Chen Yuh-Min , Yen Jiin-Cherng , Chou Yueh-Ching , Chang Yuh-Lih , He Chien-Hui
Published: September 2020

The real-world efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR-activating mutations remains unclear. We conducted a retrospective cohort study using data from the claims database of Taipei Veterans General Hospital to perform direct comparisons of these three EGFR-TKIs (gefitinib, erlotinib, and afatinib) combined with co-medications (metformin, statins, antacids, and steroids). Stage IIIB and IV NSCLC patients with EGFR mutations receiving EGFR-TKIs as first-line treatment for > 3 months between 2011 and 2016 were enrolled. The primary endpoint was time to treatment failure (TTF). Patients who had received co-medications (≥ 28 defined daily doses) in the first 3 months of EGFR-TKI therapy were assigned to co-medications groups. A total of 853 patients treated with gefitinib (n = 534), erlotinib (n = 220), and afatinib (n = 99) were enrolled. The median duration of TTF was 11.5 months in the gefitinib arm, 11.7 months in the erlotinib arm, and 16.1 months in the afatinib arm (log-rank test, P < 0.001). After adjustments, afatinib showed lower risk of treatment failure compared with gefitinib (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.41–0.71) and erlotinib (HR 0.62, 95% CI 0.46–0.83). The risk of treatment failure in patients treated with EGFR-TKIs who received concomitant systemic glucocorticoid therapy was higher than in those treated with EGFR-TKI monotherapy (HR 1.47, 95% CI 1.08–2.01). Afatinib or erlotinib use was associated with a lower risk of treatment failure in patients with advanced NSCLC harboring EGFR mutations compared to gefitinib use. Concurrent use of systemic glucocorticoids was linked to higher risk of treatment failure.
Slippery liquid infused fluoropolymer coating for central lines to reduce catheter associated clotting and infections
Authors: Bandyopadhyay Saibal , Jones Andrew , McLean Andrew , Sterner Matthew , Robbins Carolyn , Cunningham Matthew , Walters Mark , Doddapaneni Kiran , Keitel Isaac , Gallagher Colin
Published: September 2020

Thrombosis and infections are two grave, interrelated problems associated with the use of central venous catheters (CVL). Currently used antibiotic coated CVL has limited clinical success in resisting blood stream infection and may increase the risk of emerging antibiotic resistant strains. We report an antibiotic-free, fluoropolymer-immobilized, liquid perfluorocarbon-coated peripherally inserted central catheter (PICC) line and its effectiveness in reducing catheter associated thrombosis and pathogen colonization, as an alternative to antibiotic coated CVL. Commercially available polyurethane PICC catheter was modified by a three-step lamination process, with thin fluoropolymer layers to yield fluoropolymer–polyurethane–fluoropolymer composite structure before applying the liquid perfluorocarbon (LP). This high throughput process of modifying commercial PICC catheters with fluoropolymer is quicker, safer and shows higher thromboresistance than fluorinated, omniphobic catheter surfaces, produced by previously reported self-assembled monolayer deposition techniques. The LP immobilized on the fluoropolymer is highly durable in physiological flow conditions for over 60 days and continue to resist Staphylococcus colonization.
Fast responses to images of animate and inanimate objects in the nonhuman primate amygdala
Authors: Cleeren E. , Popivanov I. D. , Van Paesschen W. , Janssen Peter
Published: September 2020

Visual information reaches the amygdala through the various stages of the ventral visual stream. There is, however, evidence that a fast subcortical pathway for the processing of emotional visual input exists. To explore the presence of this pathway in primates, we recorded local field potentials in the amygdala of four rhesus monkeys during a passive fixation task showing images of ten object categories. Additionally, in one of the monkeys we also obtained multi-unit spiking activity during the same task. We observed remarkably fast medium and high gamma responses in the amygdala of the four monkeys. These responses were selective for the different stimulus categories, showed within-category selectivity, and peaked as early as 60 ms after stimulus onset. Multi-unit responses in the amygdala were lagging the gamma responses by about 40 ms. Thus, these observations add further evidence that selective visual information reaches the amygdala of nonhuman primates through a very fast route.
A general method for analyzing arbitrary planar negative-refractive-index multilayer slab optical waveguide structures
Authors: Wu Yaw-Dong
Published: September 2020

In this paper, a general method for analyzing arbitrary planar negative-refractive-index (NRI) multilayer slab optical waveguide structures was proposed. Some degenerated examples were introduced to prove the accuracy of the proposed method. The analytical and numerical results show excellent agreement. The method can also be degenerated to analyze arbitrary planar conventional optical waveguide structures. Based on this general method, the analysis and calculation of any kinds of planar NRI slab optical waveguide structures and planar conventional optical waveguide structures can be achieved easily.
Iron deficiency markers in patients undergoing iron replacement therapy: a 9-year retrospective real-world evidence study using healthcare databases
Authors: Cacoub Patrice , Nicolas Gael , Peoc’h Katell
Published: September 2020

The diagnosis and treatment of iron deficiency is a primary public health goal. This study aimed to make an inventory of the use of biomarkers to assess the iron supply in patients given iron replacement therapy. A retrospective longitudinal real-world study of a cohort of patients receiving iron replacement therapy was conducted using data from healthcare coverage databases between January 2006 and December 2015 in France. The frequency of oral or intravenous iron treatment episodes preceded and/or followed by a biological assessment of iron deficiency was described. We then differentiate patients with or without chronic inflammatory diseases, which could impact the prescription. The evolution between 2006 and 2015 was also studied. The 96,724 patients received an average of 4.9 administrations of iron per patient, corresponding to 1.7 treatment episodes. In one-third of treatment episodes (34.6%), patients had a pre-treatment biological assessment, 15.5% a post-treatment assessment, and 7.3% both. The post-treatment measure of iron supply markers (i.e., Ferritin and transferrin saturation) was more frequent in patients suffering from chronic inflammatory diseases than in those without underlying chronic condition (22.6% to 41.0% vs. 3.1%; p < 0.0001). Serum ferritin was measured 30 times more than transferrin saturation measurements. The use of both tests increased steadily during the study period, although remaining low. Despite the recommendations, biological assessments of iron status are seldom prescribed and/or performed in the context of a pre- or post-treatment assessment, although more frequently realized in patients with chronic inflammatory diseases.
A central role for the transcriptional regulator VtlR in small RNA-mediated gene regulation in Agrobacterium tumefaciens
Authors: Budnick James A. , Sheehan Lauren M. , Ginder Miranda. J. , Failor Kevin C. , Perkowski Julia. M. , Pinto John. F. , Kohl Kirsten A. , Kang Lin , Michalak Pawel , Luo Li , Heindl Jason E. , Caswell Clayton C.
Published: September 2020

LysR-type transcriptional regulators (LTTRs) are the most common type of transcriptional regulators in prokaryotes and function by altering gene expression in response to environmental stimuli. In the class Alphaproteobacteria, a conserved LTTR named VtlR is critical to the establishment of host-microbe interactions. In the mammalian pathogen Brucella abortus, VtlR is required for full virulence in a mouse model of infection, and VtlR activates the expression of abcR2, which encodes a small regulatory RNA (sRNA). In the plant symbiont Sinorhizobium meliloti, the ortholog of VtlR, named LsrB, is involved in the symbiosis of the bacterium with alfalfa. Agrobacterium tumefaciens is a close relative of both B. abortus and S. meliloti, and this bacterium is the causative agent of crown gall disease in plants. In the present study, we demonstrate that VtlR is involved in the ability of A. tumefaciens to grow appropriately in artificial medium, and an A. tumefaciens vtlR deletion strain is defective in motility, biofilm formation, and tumorigenesis of potato discs. RNA-sequencing analyses revealed that more than 250 genes are dysregulated in the ∆vtlR strain, and importantly, VtlR directly controls the expression of three sRNAs in A. tumefaciens. Taken together, these data support a model in which VtlR indirectly regulates hundreds of genes via manipulation of sRNA pathways in A. tumefaciens, and moreover, while the VtlR/LsrB protein is present and structurally conserved in many members of the Alphaproteobacteria, the VtlR/LsrB regulatory circuitry has diverged in order to accommodate the unique environmental niche of each organism.
A flavin-dependent monooxygenase catalyzes the initial step in cyanogenic glycoside synthesis in ferns
Authors: Thodberg Sara , Sørensen Mette , Bellucci Matteo , Crocoll Christoph , Bendtsen Amalie Kofoed , Nelson David Ralph , Motawia Mohammed Saddik , Møller Birger Lindberg , Neilson Elizabeth Heather Jakobsen
Published: September 2020

Cyanogenic glycosides form part of a binary plant defense system that, upon catabolism, detonates a toxic hydrogen cyanide bomb. In seed plants, the initial step of cyanogenic glycoside biosynthesis—the conversion of an amino acid to the corresponding aldoxime—is catalyzed by a cytochrome P450 from the CYP79 family. An evolutionary conundrum arises, as no CYP79s have been identified in ferns, despite cyanogenic glycoside occurrence in several fern species. Here, we report that a flavin-dependent monooxygenase (fern oxime synthase; FOS1), catalyzes the first step of cyanogenic glycoside biosynthesis in two fern species (Phlebodium aureum and Pteridium aquilinum), demonstrating convergent evolution of biosynthesis across the plant kingdom. The FOS1 sequence from the two species is near identical (98%), despite diversifying 140 MYA. Recombinant FOS1 was isolated as a catalytic active dimer, and in planta, catalyzes formation of an N-hydroxylated primary amino acid; a class of metabolite not previously observed in plants.
Mo-Doped ultrafine VC nanoparticles confined in few-layer graphitic nanocarbon for improved electrocatalytic hydrogen evolution
Authors: Cao Liyun , Zhang Ning , Feng Liangliang , He Danyang , Kajiyoshi Koji , Li Xiaoyi , Huang Qian , Feng Li , Huang Jianfeng , Li Ruizi
Published: September 2020

Developing highly efficient, durable electrocatalysts based on cheap, non-precious metals for the hydrogen evolution reaction (HER) is still the key issue in the field of hydrogen economy.
A single-component yet multifunctional tongue-mimicking sensor array for upconversion fluorescence biosensing
Authors: Wang Qian-Qian , Fang Zheng-Qi , Wu Ya-Ting , Zhang Min , Shi Guoyue
Published: September 2020

A novel single-component nanoprobe has been created for the pattern recognition of antioxidants in a “turn on” manner by integrating with the prevention of PDA formation with an antioxidant.
Solid phase extraction-based magnetic carbon nitride/metal organic framework composite with high performance liquid chromatography for the determination of tyrosine kinase inhibitors in urine samples
Authors: Liu Donghao , Peng Jun , Chen Li , Zhang Yan , Han Xiaoyang , Yang Ping , He Hua
Published: September 2020

Tyrosine kinase inhibitors were detected by MCN/BIF-20, and this is the first time that BIFs were used for solid-phase extraction.
An acidity-responsive polyoxometalate with inflammatory retention for NIR-II photothermal-enhanced chemodynamic antibacterial therapy
Authors: Shi Yunhao , Yin Jiajia , Peng Qinqin , Lv Xinyi , Li Qinzhe , Yang Dongliang , Song Xuejiao , Wang Wenjun , Dong Xiaochen
Published: September 2020

W/Mo-based polyoxometalate was developed for local photothermal-enhanced chemodynamic antibacterial therapy in the second near-infrared region.
Self-assembly of gold nanocubes into three-dimensional hollow colloidosomes and two-dimensional superlattices
Authors: Yue Xuan , Liu Xuejie , Yan Nan , Jiang Wei
Published: September 2020

Three-dimensional (3D) hollow colloidosomes and two-dimensional (2D) superlattices with highly ordered face-to-face configuration of gold nanocubes (AuNCs) can be obtained by using an “emulsion interface self-assembly” (EISA) strategy.
Quantifying active diffusion in an agitated fluid
Authors: Gires Pierre-Yves , Thampi Mithun , Weiss Matthias
Published: September 2020

Single-particle tracking reveals an enhanced diffusional motion of tracer beads when agitating the surrounding fluid with miniaturized magnetic stir bars. Signatures of the stirring are mostly encoded in correlation functions of the particle motion.
A nonsymmorphic-symmetry-protected hourglass Weyl node, hybrid Weyl node, nodal surface, and Dirac nodal line in Pd4X (X = S, Se) compounds
Authors: Meng Weizhen , Liu Ying , Zhang Xiaoming , Dai Xuefang , Liu Guodong
Published: September 2020

Nonsymmorphic symmetry has been proved to protect band crossings in topological semimetals/metals.
Impact of the radiation effect on the energy storage density and wake-up behaviors of antiferroelectric-like Al-doped HfO2 thin films
Authors: Zhang W. L. , Mao Y. H. , Cui L. , Tang M. H. , Su P. Y. , Long X. J. , Xiao Y. G. , Yan S. A.
Published: September 2020

The effect of the γ-ray total dose radiation on the energy storage density (ESD) and the phase transition of antiferroelectric-like (AFE-like) Al-doped HfO2 (HfAlO) thin films was investigated.
Janus ring siloxane: a versatile precursor of the extended Janus ring and tricyclic laddersiloxanes
Authors: Chaiprasert Thanawat , Liu Yujia , Takeda Nobuhiro , Unno Masafumi
Published: September 2020

All-cis-tetrasiloxycyclotetrasiloxanes (Janus ring siloxanes) were facilely prepared from all-cis-cyclotetrasiloxanetetraol or sodium cyclotetrasiloxane silanolates.
A polysaccharide extracted from alfalfa activates splenic B cells by TLR4 and acts primarily via the MAPK/p38 pathway
Authors: Xie Yuhuai , Wang Lixue , Sun Hua , Shang Qinghui , Wang Yuxi , Zhang Guiguo , Yang Weiren , Jiang Shuzhen
Published: September 2020

Alfalfa polysaccharide (APS) activates the immune functions of splenic B cells by TLR4, acting through the MAPK and NF-κB signaling pathways, and potently activates the p38 pathway.
A transition-metal-free multicomponent reaction towards constructing chiral 2H-1,4-benzoxazine scaffolds
Authors: Zhu Lixiang , Ren Xiaoyu , Du Juan , Wu Jia-Hong , Tan Jian-Ping , Che Jixing , Pan Jianke , Wang Tianli
Published: September 2020

A transition-metal-free multicomponent cascade reaction of α-halogenated ketones, ortho-aminophenols, and aldehydes using a dipeptide phosphonium salt catalyst was developed for the construction of various 2H-1,4-benzoxazines.
Theoretical design of new macrocycles for nucleophilic fluorination with KF: thiourea-crown-ether is predicted to overcome [2.2.2]-cryptand
Authors: Dalessandro Ellen V. , Pliego Josefredo R.
Published: September 2020

A new macrocycle combining thiourea and crown ether groups is able to solubilize KF and promote fluorination via stabilization of the SN2 transition state via four hydrogen bonds.
Au nanobipyramids@mSiO2 core–shell nanoparticles for plasmon-enhanced singlet oxygen photooxygenations in segmented flow microreactors
Authors: Mendoza Carlos , Désert Anthony , Chateau Denis , Monnereau Cyrille , Khrouz Lhoussain , Lerouge Fréderic , Andraud Chantal , Monbaliu Jean-Christophe M. , Parola Stéphane , Heinrichs Benoît
Published: September 2020

Gold nanobipyramids coated with 12 nm mSiO2 shells exhibited metal-enhanced 1O2 generation in continuous-flow photooxygenation reactions.
Janus nanoparticles designed for extended cell surface attachment
Authors: Kadam Reshma , Ghawali Jaee , Waespy Mario , Maas Michael , Rezwan Kurosch
Published: September 2020

DSPE/PEG-coated Janus nanoparticles firmly anchor onto cell surfaces by a process that involves incomplete macropinocytosis.
Highly selective conversion of CO2 to methanol on the CuZnO–ZrO2 solid solution with the assistance of plasma
Authors: Han Fennv , Liu Huaiping , Cheng Wenqiang , Xu Qi
Published: September 2020

CuZnO–ZrO2–C was prepared by a co-precipitation method.
DFT study of α-Keggin, lacunary Keggin, and ironII–VI substituted Keggin polyoxometalates: the effect of oxidation state and axial ligand on geometry, electronic structures and oxygen transfer
Authors: Mir Soheila , Yadollahi Bahram , Omidyan Reza , Azimi Gholamhasan
Published: September 2020

Herein, the geometry, electronic structure, Fe–ligand bonding nature and simulated IR spectrum of α-Keggin, lacunary Keggin and iron(ii–vi)-substituted Keggin type polyoxometalates have been studied using the DFT/OPTX-PBE method and NBO analysis.
Functional nanostructure-loaded three-dimensional graphene foam as a non-enzymatic electrochemical sensor for reagentless glucose detection
Authors: Liu Qianshi , Zhong Huage , Chen Miao , Zhao Chang , Liu Yan , Xi Fengna , Luo Tao
Published: September 2020

A non-enzymatic electrochemical sensor was fabricated by loading functional nanostructure on three-dimensional graphene foam for reagentless detection of glucose with high sensitivity and stability.
Effect of curing conditions on the cutting resistance of fabrics coated with inorganic-powder-reinforced epoxy composite
Authors: Yan Xuefeng , Wu Leilei , Jin Shanshan , Zhao Wei , Cao Haijian , Ma Yan
Published: September 2020

Inorganic powders, SiO2 and Al2O3, were used as reinforcements and thermosetting epoxy resin was utilized as a matrix to manufacture IP/epoxy preform, which was coated on the surfaces of 2/1 twill woven polyethylene terephthalate fabrics before the final curing process.
A biocompatible supramolecular hydrogel with multivalent galactose ligands inhibiting Pseudomonas aeruginosa virulence and growth
Authors: Liu Shengnan , Li Hang , Zhang Jikun , Tian Xin , Li Xinming
Published: September 2020

A glycopeptide hydrogel displaying galactoses on their surface was prepared, which inhibited Pseudomonas aeruginosa virulence and growth through multivalent interactions.
Chemoselective and metal-free reduction of α,β-unsaturated ketones by in situ produced benzeneselenol from O-(tert-butyl) Se-phenyl selenocarbonate
Authors: Temperini Andrea , Ballarotto Marco , Siciliano Carlo
Published: September 2020

The carbon–carbon double bond of arylidene acetones and chalcones can be selectively reduced with benzeneselenol generated in situ by reacting O-(tert-butyl) Se-phenyl selenocarbonate with hydrochloric acid in ethanol.
Neuraldecipher – reverse-engineering extended-connectivity fingerprints (ECFPs) to their molecular structures
Authors: Le Tuan , Winter Robin , Noé Frank , Clevert Djork-Arné
Published: September 2020

Protecting molecular structures from disclosure against external parties is of great relevance for industrial and private associations, such as pharmaceutical companies.
Decoding the intricate network of molecular interactions of a hyperstable engineered biocatalyst
Authors: Markova Klara , Chmelova Klaudia , Marques Sérgio M. , Carpentier Philippe , Bednar David , Damborsky Jiri , Marek Martin
Published: September 2020

Illustration of cooperative thermostabilization effects of the double-lock system that: (i) induced backbone changes, (ii) closed the molecular gates, (iii) reduced the volumes of the main and slot access tunnels, and (iv) occluded the active site.
Recent advances of non-fullerene organic electron transport materials in perovskite solar cells
Authors: Wang Daizhe , Ye Tengling , Zhang Yong
Published: September 2020

The advances of non-fullerene ETMs in PerSCs and their design strategies were systematically summarized.
Resilient biomass-derived hydrogel with tailored topography for highly efficient and long-term solar evaporation of high-salinity brine
Authors: Chen Xiaoxiao , Wu Zhiying , Lai Dengguo , Zheng Min , Xu Lei , Huo Jiangbo , Chen Zhangxu , Yuan Baoling , Fu Ming-Lai
Published: September 2020

A sponge-like biomass-derived hydrogel is constructed via a facile and scalable strategy, and exhibits promising applications in solar-driven seawater desalination, zero-liquid discharge and solute recovery.