bluuebunny/crossref_metadata_2025 huggingface dataset:
Language impairment in an Italian child with Trisomy X
Authors: Lantschner Natascha , Cardinaletti Anna
Published: May 2020

This study deals with the case of Emma, an Italian 8-year-old girl affected by a sex chromosome anomaly called Trisomy X and diagnosed with Expressive Language Impairment. Language assessment of both comprehension and production was conducted through standardized and non-standardized, experimental tests. Passive, cleft, wh-sentences, and relative clauses with manipulation of number features were tested, in addition to clitic pronouns. Her spontaneous production was also assessed. Emma has problems with functional words realizing the highest portion of nominal structure: articles, prepositions, and clitic pronouns. Given her very good cognitive abilities, Emma was administered a tailor-made language intervention focused on functional elements, namely determiners and prepositions, aimed at enhancing her language awareness. During language intervention, use of Italian Sign Language (LIS) was crucial to boost lexical retrieval of functional prepositions and pluri-syllabic lexical words.
Sentence reading in older adults with and without Mild Cognitive Impairment
Authors: Martín-Aragoneses María Teresa , del Río Grande David , López-Higes Sánchez Ramón , Prados Atienza José María , Montejo Carrasco Pedro , Delgado-Losada María Luisa
Published: May 2020

While language comprehension tends to be well preserved in older adults, the processing and comprehension of syntactically complex sentences might be influenced by age-related changes in Working Memory (WM) and Interference Control (IC). Further, aging can be accompanied by cognitive decline caused by neurological conditions such as Mild Cognitive Impairment (MCI), but its impact on on-line sentence processing has rarely been studied. We report a study of word-by-word reading times and comprehension of sentences with different syntactic complexity in young adults (n = 69) and two subgroups of older adults: healthy older adults (n = 32) and older adults with single- and multi-domain amnestic MCI (n = 21). The experimental protocol was based on a self-paced reading task and a variety of neuropsychological measures including Operation Span (WM) and Stroop (IC) tasks. Syntactic complexity was induced using Spanish embedded relative clauses varying subject- versus object-extraction of the antecedent noun phrase (canonical or non-canonical word order, respectively). Moreover, within non-canonical sentences, we distinguished between those that did or did not contain long-distance dependencies between the extracted object and embedded verb. All these manipulations were expected to lead to a gradual recruitment of IC and WM based on the complexity of the sentence structure. Comprehension was similar across groups, with differences explained by WM capacity. In both subgroups of older adults, the on-line processing of object extracted sentences was modulated by their available IC and WM resources, although older adults with MCI seem to recruit WM to a lesser extent. In conclusion, results suggest that IC and WM have a modulatory role in the processing and comprehension of syntactically complex sentences in older adults. Moreover, older adults with MCI seem to be particularly overwhelmed by WM demands during sentence processing and comprehension.
The comprehension of wh-questions and passives in German children and adolescents with Down syndrome
Authors: Wimmer Eva , Penke Martina
Published: May 2020

Children with Down syndrome (DS) have difficulty comprehending complex syntactic structures. Ring and Clahsen (2005) attribute these problems to a specific syntactic deficit that affects A(=argument) movement. We investigated the comprehension of passive sentences (A-movement) and wh-questions (wh-movement) in 22 German children and adolescents with DS compared to mental-age matched typically developing children. The results suggest that an impairment in the syntactic development affecting also wh-movement structures occurs in a substantial proportion of children with DS and exceeds their general cognitive disabilities. The error patterns of both tests reveal problems with non-canonical clauses and the use of the Agent-first strategy as in early stages of typical acquisition. Moreover, limitations in phonological working memory might contribute to syntactic processing problems in individuals with DS.
The distribution of null subjects in Chinese discourse
Authors: Chen Shuangshuang (Lillian)
Published: May 2020

Chinese is described as a null subject language, in that the
subject of a clause can be unexpressed (covert). While a large amount of previous
literature has focused on null subjects in isolated sentences, this study is
concerned with null subjects in Chinese written narrative discourse within the
framework of the Centering Theory. I examined the distribution of null subjects
and their antecedents to explore the properties of null subjects, especially the
relation between the function of null subjects and centering transitions. My
hypothesis that the use of null subjects strongly relates to the CONTINUE
transition is basically supported. Specifically, 96.48% are referential null
subjects. Besides, I found that null subjects can also occur in other transition
types, particularly in SMOOTH transitions (52.59%). The difference is that null
subjects in CONTINUE transitions are overwhelmingly referential null subjects
(96.48%), while they are non-referential null subjects (60.66%) in SMOOTH
transitions.
The acceptability of 把 ba+subject-oriented resultatives in
Mandarin Chinese
Authors: Yu Shuo
Published: May 2020

The combination of 把 ba and subject-oriented
resultative constructions in Mandarin Chinese, which is not always well accepted
by native speakers, has so far received little scholarly attention. To test the
acceptability of 把 ba + subject-oriented resultatives
in Chinese, based on examples in the corpora, a questionnaire survey among 71
Chinese college students was carried out with the technique of magnitude
estimation, which could detect small but significant differences in acceptability.
The results suggest that the acceptability of 把 ba + subject-oriented resultatives
depends on the degree of transitivity of the sentence. In general, patterns with
the interpretation of the subject making efforts to achieve something thoroughly
are acceptable. The cognitive explanation I propose is that a high degree of
transitivity expressed by the sentence is compatible with the function of
把 ba as a marker of high
transitivity.
Gender representation in Chinese language
Authors: Li Lan
Published: May 2020

Different from Romanized languages with gender marker, the
Chinese language does not have inflections in nouns, adjectives and verbs when the
subject is a female. Instead, a semantic stem or the radical
woman 女 (nü) is used to directly
indicate femininity. This study takes a lexicographic and corpus approach to
explore gender representation in Chinese and discusses its forms, meanings and
usages. First, characters with the radical woman were classified
into different semantic fields to see how they represent women and reflect social
ideologies. Second, their representations in a modern Chinese dictionary were
compared with a classic one to see the historical change. Third, the use of the
words was explored in a mega-corpus of 287 million Chinese characters. It is
interesting to see that more than 70% of the characters with the radical
女
(nü, woman) listed in classic Chinese dictionaries have
vanished in modern society probably due to language evolution and social-cultural
changes such as a shift in attitudes towards women. A few characters changed their
female semantic element to a gender-neutral one. Gender representation in Chinese
is also reflected in Chinese idioms, the word order and gendered third-person
pronoun. Understanding these forms can provide insight into Chinese culture and
raise awareness of shifting trends of their use in the language.
Hyperhomocysteinemia-Induced Oxidative Stress Aggravates Renal Damage in Hypertensive Rats
Authors: Gao Ning , Zhang Yuzhen , Li Li , Lei Lei , Cao Ping , Zhao Xuan , Lin Lin , Xu Rui
Published: May 2020

BACKGROUND

Hyperhomocysteinemia (HHcy) plays a synergistic role with hypertension in vascular injury; however, the relationship between HHcy and hypertension in renal injury remains unclear. Here, we sought to evaluate the relationship between HHcy and hypertension in the context of renal injury and to elucidate the mechanism of action underlying this relationship.

METHODS

Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were randomized into WKY, WKY + HHcy, SHR, and SHR + HHcy groups. Blood pressure, plasma homocysteine, serum malondialdehyde (MDA), serum superoxide dismutase (SOD), urinary albumin creatinine ratio (UACR), and glomerular filtration rate (GFR) were measured. Renal histopathology and expression levels of NOX2, NOX4, and nephrin in the kidneys were examined.

RESULTS

The WKY + HHcy and SHR groups exhibited lower serum SOD and GFR levels, relative to the WKY group, along with higher levels of both serum MDA and UACR. Higher mRNA and protein expression levels of NOX2 and NOX4, along with lower expression levels of nephrin, were observed in the kidneys of WKY + HHcy and SHR rats, relative to WKY controls, respectively. Similar effects were observed in the SHR + HHcy group, relative to the SHR group and WKY + HHcy group, respectively. Periodic acid-Schiff staining showed an increase in the glomerular extracellular matrix in the WKY + HHcy and SHR + HHcy groups compared with their respective controls.

CONCLUSIONS

HHcy appears to synergistically increase hypertensive renal damage by enhancing oxidative stress.
MiR-17 Knockdown Promotes Vascular Smooth Muscle Cell Phenotypic Modulation Through Upregulated Interferon Regulator Factor 9 Expression
Authors: Li Wenyan , Deng Ping , Wang Junhua , Li Zhaofeng , Zhang Huming
Published: May 2020

BACKGROUND

MiR-17 is a small noncoding RNA that plays an important role in the development of tumorgenesis, which recently has emerged to be involved in regulation of inflammatory responses and angiogenesis. However, the effect and underlying mechanism of miR-17 on vascular smooth muscle cell (VSMC) phenotypic modulation have not been investigated.

METHODS AND RESULTS

In the current study, we observed that miR-17 expression tested by real-time polymerase chain reaction (RT-PCR) was downregulated in VSMCs administrated with platelet-derived growth factor-BB stimulation and carotid arteries subjected to wire injury, which were accompanied with decreased VSMC differentiation markers. Loss-of-function strategy demonstrated that miR-17 knockdown promoted VSMC phenotypic modulation characterized as decreased VSMC differentiation marker genes, increased proliferated and migrated capability of VSMC examined by RT-PCR and western blot analysis. Mechanistically, the bioinformatics analysis and luciferase assay demonstrated that miR-17 directly targeted Interferon Regulator Factor 9 (IRF9) and the upregulated IRF9 expression was responsible for the promoted effect miR-17 knockdown on VSMC phenotypic modulation.

CONCLUSIONS

Taken together, our results demonstrated that miR-17 knockdown accelerated VSMC phenotypic modulation partially through directly targeting to IRF9, which suggested that miR-17 may act as a novel therapeutic target for intimal hyperplasia management.
Chronic Alcohol Intake Exacerbates Cardiac Dysfunction After Myocardial Infarction
Authors: Liang Yu , Xu Xuewen , Li Qin , Deng Yan , Xie Maodi , Zheng Yanyi , Ou Wei , He Qinqin , Xu Xiaoyan , Wu Wei , Li Tao
Published: May 2020

Aims

Alcohol intake is a risk factor for cardiovascular diseases. This study was designed to investigate whether chronic alcohol intake affects myocardial infarction (MI)-induced cardiac remodeling and heart failure.

Methods

Eight-week-old male C57BL/6 mice were randomly divided into four groups: Sham group (Sham), MI plus drinking water group (MI + Vehicle), and MI plus daily alcohol intake for 6 weeks with or without gavage of additional alcohol every 3 days (MI + Alcohol and MI + Alcohol + G). The MI were induced by permanent left anterior descending (LAD) coronary artery ligation surgery before vehicle or alcohol treatment. The blood alcohol concentration (BAC), cardiac function, release of cardiac enzymes, pathological changes and mitochondrial function were measured.

Results

As expected, supplementation of alcohol in drinking water significantly increased random BAC in mice. Long-term exposure to alcohol further reduced body weight, ejection fraction and fractional shortening in comparison with the MI + Vehicle group. Histopathological data showed that alcohol increased fibrosis in infarct zone, which was well correlated with the functional decline. Also, as compared to the MI + Vehicle group, the adenosine diphosphate-supported respiratory function of freshly isolated cardiac mitochondria was inhibited in the MI + Alcohol + G group. Besides, upon MI-induced cardiac damage, we did not observe further changes in heart weight, cardiomyocyte enlargement in remote zone, exercise capacity, lung edema and the release of cardiac enzyme after chronic alcohol intake.

Conclusions

Our study demonstrated that chronic daily alcohol exposure exacerbated MI-induced cardiac dysfunction, which is related to promoted myocardial fibrosis and inhibited mitochondrial function.
Colony size affects breeding density, but not spatial distribution type, in a seabird
Authors: Bouwhuis Sandra , Ballani Felix , Bourgeois Marie , Stoyan Dietrich
Published: May 2020

The spatial distribution of individuals within populations can result in fine-scale density dependence and affect the social environment that is encountered. As such, it is important to quantify within-population spatial structuring and understand the factors that shape it. In this study, we make use of point process statistics to test whether colony size affects the statistical type of spatial nest distribution produced by common terns (Sterna hirundo) breeding at identical manmade rectangular and homogeneous islands of fixed physical size. Comparing subcolonies of variable density both within and across years, we find that inter-nest distances are smaller at higher local and overall breeding density, but that the spatial distribution type does not vary across the observed densities. This suggests that the birds’ main settlement rules do not depend on density. In our case, analyses of fine-scale density dependence or potential social effects therefore do not need to account for between-individual heterogeneity in settlement decision rules or acceptance of these rules. We urge, however, other studies to similarly test for density dependence of the spatial distribution of individuals before undertaking such “downstream” analyses.
Partial Support for an Interaction Between a Polygenic Risk Score for Major Depressive Disorder and Prenatal Maternal Depressive Symptoms on Infant Right Amygdalar Volumes
Authors: Acosta H , Kantojärvi K , Hashempour N , Pelto J , Scheinin N M , Lehtola S J , Lewis J D , Fonov V S , Collins D L , Evans A , Parkkola R , Lähdesmäki T , Saunavaara J , Karlsson L , Merisaari H , Paunio T , Karlsson H , Tuulari J J
Published: May 2020

Psychiatric disease susceptibility partly originates prenatally and is shaped by an interplay of genetic and environmental risk factors. A recent study has provided preliminary evidence that an offspring polygenic risk score for major depressive disorder (PRS-MDD), based on European ancestry, interacts with prenatal maternal depressive symptoms (GxE) on neonatal right amygdalar (US and Asian cohort) and hippocampal volumes (Asian cohort). However, to date, this GxE interplay has only been addressed by one study and is yet unknown for a European ancestry sample. We investigated in 105 Finnish mother–infant dyads (44 female, 11–54 days old) how offspring PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant amygdalar and hippocampal volumes. We found a GxE effect on right amygdalar volumes, significant in the main analysis, but nonsignificant after multiple comparison correction and some of the control analyses, whose direction paralleled the US cohort findings. Additional exploratory analyses suggested a sex-specific GxE effect on right hippocampal volumes. Our study is the first to provide support, though statistically weak, for an interplay of offspring PRS-MDD and prenatal maternal depressive symptoms on infant limbic brain volumes in a cohort matched to the PRS-MDD discovery sample.
Clinical and In Vitro Resistance of Plasmodium falciparum to Artesunate-Amodiaquine in Cambodia
Authors: Mairet-Khedim Melissa , Leang Rithea , Marmai Camille , Khim Nimol , Kim Saorin , Ke Sopheakvatey , Kauy Chhayleang , Kloeung Nimol , Eam Rotha , Chy Sophy , Izac Brigitte , Mey Bouth Denis , Dorina Bustos Maria , Ringwald Pascal , Ariey Frederic , Witkowski Benoit
Published: May 2020

Background

Artesunate-amodiaquine is a potential therapy for uncomplicated malaria in Cambodia.

Methods

Between September 2016 and January 2017, artesunate-amodiaquine efficacy and safety were evaluated in a prospective, open-label, single-arm observational study at health centers in Mondulkiri, Pursat, and Siem Reap Provinces, Cambodia. Adults and children with microscopically confirmed Plasmodium falciparum malaria received oral artesunate-amodiaquine once daily for 3 days plus single-dose primaquine, with follow-up on days 7, 14, 21, and 28. The primary outcome was day-28 polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR). An amodiaquine parasite survival assay (AQSA) was developed and applied to whole genome sequencing results to evaluate potential amodiaquine resistance molecular markers.

Results

In 63 patients, day-28 PCR-adjusted ACPR was 81.0% (95% confidence interval [CI], 68.9–88.7). Day 3 parasite positivity rate was 44.4% (28/63; 95% CI, 31.9–57.5). All 63 isolates had the K13(C580Y) marker for artemisinin resistance; 79.4% (50/63) had Pfpm2 amplification. The AQSA resistance phenotype (≥45% parasite survival) was expressed in 36.5% (23/63) of isolates and was significantly associated with treatment failure (P = .0020). Pfmdr1 mutant haplotypes were N86/184F/D1246, and Pfcrt was CVIET or CVIDT at positions 72–76. Additional Pfcrt mutations were not associated with amodiaquine resistance, but the G353V mutant allele was associated with ACPR compared to Pfmdr1 haplotypes harboring F1068L or S784L/R945P mutations (P = .030 and P = .0004, respectively).

Conclusions

For uncomplicated falciparum malaria in Cambodia, artesunate-amodiaquine had inadequate efficacy owing to amodiaquine-resistant P. falciparum. Amodiaquine resistance was not associated with previously identified molecular markers.
The Urgent Need for Medicare Reimbursement for Home Infusion Antibiotics Amidst a Pandemic
Authors: Streifel Amber C , Sikka Monica K
Published: May 2020

Medicare does not reimburse for home infusion; patients requiring outpatient parenteral antimicrobial therapy must seek treatment in high-risk settings. We recommend policy change to allow for adequate social distancing during the coronavirus disease 2019 pandemic.
ForageGrassBase: molecular resource for the forage grass meadow fescue (Festuca pratensis Huds.)
Authors: Samy Jeevan Karloss Antony , Rognli Odd Arne , Kovi Mallikarjuna Rao
Published: May 2020

Meadow fescue (Festuca pratensis Huds.) is one of the most important forage grasses in temperate regions. It is a diploid (2n = 14) outbreeding species that belongs to the genus Festuca. Together with Lolium perenne, they are the most important genera of forage grasses. Meadow fescue has very high quality of yield with good winter survival and persistency. However, extensive genomic resources for meadow fescue have not become available so far. To address this lack of comprehensive publicly available datasets, we have developed functionally annotated draft genome sequences of two meadow fescue genotypes, ‘HF7/2’ and ‘B14/16’, and constructed the platform ForageGrassBase, available at http://foragegrass.org/, for data visualization, download and querying. This is the first open-access platform that provides extensive genomic resources related to this forage grass species. The current database provides the most up-to-date draft genome sequence along with structural and functional annotations for genes that can be accessed using Genome Browser (GBrowse), along with comparative genomic alignments to Arabidopsis, L. perenne, barley, rice, Brachypodium and maize genomes. We have integrated homologous search tool BLAST also for the users to analyze their data. Combined, GBrowse, BLAST and downloadable data gives a user-friendly access to meadow fescue genomic resources. To our knowledge, ForageGrassBase is the first genome database dedicated to forage grasses. The current forage grass database provides valuable resources for a range of research fields related to meadow fescue and other forage crop species, as well as for plant research communities in general. The genome database can be accessed at http://foragegrass.org.
Meta-analysis of prognostic factors of overall survival in patients undergoing oesophagectomy for oesophageal cancer
Authors: Kamarajah Sivesh K , Marson Ella J , Zhou Dengyi , Wyn-Griffiths Freddie , Lin Aaron , Evans Richard P T , Bundred James R , Singh Pritam , Griffiths Ewen A
Published: May 2020

Introduction

Currently, the American Joint Commission on Cancer (AJCC) staging system is used for prognostication for oesophageal cancer. However, several prognostically important factors have been reported but not incorporated. This meta-analysis aimed to characterize the impact of preoperative, operative, and oncological factors on the prognosis of patients undergoing curative resection for oesophageal cancer.

Methods

This systematic review was performed according to PRISMA guidelines and eligible studies were identified through a search of PubMed, Scopus, and Cochrane CENTRAL databases up to 31 December 2018. A meta-analysis was conducted with the use of random-effects modeling to determine pooled univariable hazard ratios (HRs). The study was prospectively registered with the PROSPERO database (Registration: CRD42018157966).

Results

One-hundred and seventy-one articles including 73,629 patients were assessed quantitatively. Of the 122 factors associated with survival, 39 were significant on pooled analysis. Of these. the strongly associated prognostic factors were ‘pathological’ T stage (HR: 2.07, CI95%: 1.77–2.43, P < 0.001), ‘pathological’ N stage (HR: 2.24, CI95%: 1.95–2.59, P < 0.001), perineural invasion (HR: 1.54, CI95%: 1.36–1.74, P < 0.001), circumferential resection margin (HR: 2.17, CI95%: 1.82–2.59, P < 0.001), poor tumor grade (HR: 1.53, CI95%: 1.34–1.74, P < 0.001), and high neutrophil:lymphocyte ratio (HR: 1.47, CI95%: 1.30–1.66, P < 0.001).

Conclusion

Several tumor biological variables not included in the AJCC 8th edition classification can impact on overall survival. Incorporation and validation of these factors into prognostic models and next edition of the AJCC system will enable personalized approach to prognostication and treatment.
Management of non-culprit coronary plaques in patients with acute coronary syndrome
Authors: Montone Rocco A. , Niccoli Giampaolo , Crea Filippo , Jang Ik-Kyung
Published: May 2020

Approximately 50% of patients with ST-segment elevation myocardial infarction (STEMI) have multivessel coronary artery disease, a condition associated with an increased incidence of recurrent ischaemic events and higher mortality. Based on recent evidences, a strategy of staged percutaneous coronary intervention (PCI) of obstructive non-culprit lesions should be considered the gold standard for the management of these patients. However, several issues remain still unresolved. Indeed, what is the optimal timing of staged PCI is not completely defined. Moreover, assessment of intermediate non-culprit lesions represent still a clinical conundrum, as pressure-wire indexes do not seem able to correctly identify those patients in whom deferral is safe. Intracoronary imaging may help to identify untreated non-culprit lesions containing vulnerable plaques that may portend a higher risk of future cardiovascular events. However, there are hitherto no studies demonstrating that preventive PCI of vulnerable plaques or more intensive pharmacological treatment is associated with an improved clinical outcome. In this review, we discuss the recent evolving concepts about management of non-culprit plaques in STEMI patients, proposing a diagnostic and therapeutic algorithm to guide physicians in clinical practice. We also underscore the several knowledge gaps to address in future studies.
Patient-centered communication and emotional well-being in the era of medical violence in China
Authors: Jiang Shaohai , Hong Y Alicia
Published: May 2020

The past decade has witnessed an increasing number of patient assaults on doctors in China. Patient-centered communication (PCC) may be one way to mitigate this problem. This study examined the effects of PCC and patient trust on emotional health outcome, especially how patients’ attitude toward medical violence affected this relationship. Data were drawn from the China Governance and Public Policy Survey administered in 2017 with a sample size of 3784. The results showed that PCC had no direct effect on emotional well-being. Instead, patient trust completely mediated this path. Also, patients’ attitude toward medical violence increased the indirect effect of PCC on emotional well-being, suggesting a moderated mediation model. We call for education programs to promote PCC for both providers and patients, mass media campaigns to condemn violence against doctors and stricter law enforcement to stop medical violence.
The Genetic Architecture of Plant Defense Trade-offs in a Common Monkeyflower
Authors: Kooyers Nicholas J , Donofrio Abigail , Blackman Benjamin K , Holeski Liza M
Published: May 2020

Determining how adaptive combinations of traits arose requires understanding the prevalence and scope of genetic constraints. Frequently observed phenotypic correlations between plant growth, defenses, and/or reproductive timing have led researchers to suggest that pleiotropy or strong genetic linkage between variants affecting independent traits is pervasive. Alternatively, these correlations could arise via independent mutations in different genes for each trait and extensive correlational selection. Here we evaluate these alternatives by conducting a quantitative trait loci (QTL) mapping experiment involving a cross between 2 populations of common monkeyflower (Mimulus guttatus) that differ in growth rate as well as total concentration and arsenal composition of plant defense compounds, phenylpropanoid glycosides (PPGs). We find no evidence that pleiotropy underlies correlations between defense and growth rate. However, there is a strong genetic correlation between levels of total PPGs and flowering time that is largely attributable to a single shared QTL. While this result suggests a role for pleiotropy/close linkage, several other QTLs also contribute to variation in total PPGs. Additionally, divergent PPG arsenals are influenced by a number of smaller-effect QTLs that each underlie variation in 1 or 2 PPGs. This result indicates that chemical defense arsenals can be finely adapted to biotic environments despite sharing a common biochemical precursor. Together, our results show correlations between defense and life-history traits are influenced by pleiotropy or genetic linkage, but genetic constraints may have limited impact on future evolutionary responses, as a substantial proportion of variation in each trait is controlled by independent loci.
Stereotactic body radiotherapy in patients with early-stage non-small cell lung cancer: Does beam-on time matter?
Authors: Hurmuz Pervin , Cengiz Mustafa , Ozyigit Gokhan , Akkas Ebru Atasever , Yuce Deniz , Yilmaz Melek Tugce , Yildiz Demet , Zorlu Faruk , Akyol Fadil
Published: May 2020

Purpose

Stereotactic body radiotherapy (SBRT) is an effective treatment option for patients with early-stage non-small cell lung cancer (NSCLC). In this study, we evaluated the treatment results using two different SBRT techniques and the effect of beam-on time (BOT) on treatment outcomes.

Methods

Between July 2007 and January 2018, 142 patients underwent SBRT for primary NSCLC. We have delivered SBRT using either respiratory tracking system (RTS) or internal-target-volume (ITV)-based motion management techniques. The effect of age, tumor size, pretreatment tumor SUVmax value, presence of tissue diagnosis, histopathological subtype, operability status, tumor location, motion management technique, BED10 value, BOT on overall survival (OS), loco-regional control (LRC), event-free survival (EFS) and primary tumor control (PTC) were evaluated.

Results

Median age of the patients was 70 years (range, 39–91 years). Most of the patients were inoperable (90%) at the time of SBRT. Median BED10 value was 112.5 Gy. With a median follow-up of 25 months, PTC was achieved in 91.5% of the patients. Two-year estimated OS, LRC, PTC and EFS rates were 68, 63, 63 and 53%, respectively. For the entire group, OS was associated with BOT (P = 0.027), and EFS was associated with BOT (P = 0.027) and tumor size (P = 0.015). For RTS group, OS was associated with age (P = 0.016), EFS with BOT (P = 0.05) and tumor size (P = 0.024), LRC with BOT (P = 0.008) and PTC with BOT (P = 0.028). The treatment was well tolerated in general.

Conclusion

SBRT is an effective and safe treatment with high OS, LRC, EFS and PTC rates in patients with primary NSCLC. Protracted BOT might deteriorate SBRT outcomes.
Electrostatic potential imaging of phase-separated structures in organic materials via differential phase contrast scanning transmission electron microscopy
Authors: Inamoto Shin , Shimomura Satoru , Otsuka Yuji
Published: May 2020

Electron staining is generally performed prior to observing organic materials via transmission electron microscopy (TEM) to enhance image contrast. However, electron staining can deteriorate organic materials. Here, we demonstrate electrostatic potential imaging of organic materials via differential phase contrast (DPC) scanning transmission electron microscopy (STEM) without electron staining. Electrostatic potential imaging drastically increases the contrast between different materials. Phase-separated structures in a poly (3-hexylthiophene) (P3HT) and [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) blend that are impossible to observe using conventional STEM are clearly visualized. Furthermore, annealing behavior of the phase-separated structures is directly observed. The morphological transformations in the samples are consistent with their physical parameters, including their glass transition and melting temperatures. Our results indicate that electrostatic potential imaging is highly effective for observing organic materials.
Vascularized tendon graft to the central slip using a finger fillet flap
Authors: Rogozinski Jonathan , Johnson R Michael
Published: May 2020

Burn boutonniere deformity (BBD) treatment remains a challenge in reconstructive surgery. Severe hand defects after burn/trauma may be reconstructed with nonsalvageable or amputated tissue. The fillet flap (FF) is generally used as “spare parts” in the trauma algorithm for mangled extremities. This case study examines the use of a FF with concurrent repair of the adjacent finger extensor tendon with the amputated finger flexor tendon after burn injury. The goal is to provide adequate tissue coverage using a finger FF while concurrently reconstructing the central slip of the extensor tendon with the transposed flexor tendon from an adjacent nonfunctional digit. After reconstruction, no subluxation of the extensor tendon occurred with manipulation. Despite prolonged rehabilitation due to injuries, the surgical site healed appropriately. Single-stage FF reconstruction with vascularized tendon grafts should be considered in selected patients with BBD. This novel idea can be applied to the management of traumatized extremities.
Compatibility of X-ray computed tomography with plant gene expression, rhizosphere bacterial communities and enzyme activities
Authors: Ganther Minh , Yim Bunlong , Ibrahim Zeeshan , Bienert Manuela Desiree , Lippold Eva , Maccario Lorrie , Sørensen Søren Johannes , Bienert Gerd Patrick , Vetterlein Doris , Heintz-Buschart Anna , Blagodatskaya Evgenia , Smalla Kornelia , Tarkka Mika T
Published: May 2020

Non-invasive X-ray computed tomography (XRCT) is increasingly used in rhizosphere research to visualize development of soil–root interfaces in situ. However, exposing living systems to X-rays can potentially impact their processes and metabolites. In order to evaluate these effects, we assessed the responses of rhizosphere processes 1 and 24 h after a low X-ray exposure (0.81 Gy). Changes in root gene expression patterns occurred 1 h after exposure with down-regulation of cell wall-, lipid metabolism-, and cell stress-related genes, but no differences remained after 24 h. At either time point, XRCT did not affect either root antioxidative enzyme activities or the composition of the rhizosphere bacterial microbiome and microbial growth parameters. The potential activities of leucine aminopeptidase and phosphomonoesterase were lower at 1 h, but did not differ from the control 24 h after exposure. A time delay of 24 h after a low X-ray exposure (0.81 Gy) was sufficient to reverse any effects on the observed rhizosphere systems. Our data suggest that before implementing novel experimental designs involving XRCT, a study on its impact on the investigated processes should be conducted.
Time to exploit phenotypic plasticity
Authors: Monforte Antonio J
Published: May 2020

This article comments on:

Diouf I, Derivot L, Koussevitzky S, Carretero Y, Bitton F, Moreau L, Causse M. 2020. Genetic basis of phenotypic plasticity and genotype×environment interaction in a multi-parental tomato population. Journal of Experimental Botany 71, 5365–5376.
Dynamical self-friction: how mass loss slows you down
Authors: Miller Tim B , van den Bosch Frank C , Green Sheridan B , Ogiya Go
Published: May 2020

We investigate dynamical self-friction, the process by which material that is stripped from a subhalo torques its remaining bound remnant, which causes it to lose orbital angular momentum. By running idealized simulations of a subhalo orbiting within an analytical host halo potential, we isolate the effect of self-friction from traditional dynamical friction due to the host halo. While at some points in a subhalo’s orbit the torque of the stripped material can boost the orbital angular momentum of the remnant, the net effect over the long term is orbital decay regardless of the initial orbital parameters or subhalo mass. In order to quantify the strength of self-friction, we run a suite of simulations spanning typical host-to-subhalo mass ratios and orbital parameters. We find that the time-scale for self-friction, defined as the exponential decay time of the subhalo’s orbital angular momentum, scales with mass ratio and orbital circularity similar to standard dynamical friction. The decay time due to self-friction is roughly an order of magnitude longer, suggesting that self-friction only contributes at the 10 per cent level. However, along more radial orbits, self-friction can occasionally dominate over dynamical friction close to pericentric passage, where mass stripping is intense. This is also the epoch at which the self-friction torque undergoes large and rapid changes in both magnitude and direction, indicating that self-friction is an important process to consider when modelling pericentric passages of subhaloes and their associated satellite galaxies.
Thiazide diuretics and the rate of disease progression in autosomal dominant polycystic kidney disease: an observational study
Authors: Kramers Bart J , Koorevaar Iris W , De Boer Rudolf , Hoorn Ewout J , Pena Michelle J , Gansevoort Ron T , Meijer Esther ,   the DIPAK Consortium
Published: May 2020

Background

In autosomal dominant polycystic kidney disease (ADPKD), hypertension is prevalent and cardiovascular events are the main cause of death. Thiazide diuretics are often prescribed as second-line antihypertensives, on top of renin–angiotensin–aldosterone system (RAAS) blockade. There is a concern, however, that diuretics may increase vasopressin concentration and RAAS activity, thereby worsening disease progression in ADPKD. We aimed to investigate the validity of these suggestions.

Methods

We analysed an observational cohort of 533 ADPKD patients. Plasma copeptin (surrogate for vasopressin), aldosterone and renin were measured by enzyme-linked immunosorbent assay and radioimmunoassay, respectively. Linear mixed models were used to assess the association of thiazide use with estimated glomerular filtration rate (eGFR) decline and Cox proportional hazards models for the association with the composite kidney endpoint of incident end-stage kidney disease, 40% eGFR decline or death.

Results

A total of 23% of participants (n = 125) used thiazide diuretics at baseline. Compared with non-users, thiazide users were older, a larger proportion was male, they had lower eGFRs and similar blood pressure under more antihypertensives. Plasma copeptin was higher, but this difference disappeared after adjustment for age and sex. Both renin and aldosterone were higher in thiazide users. There was no difference between thiazide users and non-users in the rate of eGFR decline {difference −0.35 mL/min/1.73 m2 per year [95% confidence interval (CI) −0.83 to –0.14], P = 0.2} during 3.9 years of follow-up (interquartile range 2.5–4.9). This did not change after adjustment for potential confounders [difference final model: 0.08 mL/min/1.73 m2 per year [95% CI −0.46 to –0.62], P = 0.8). In the crude model, thiazide use was associated with a higher incidence of the composite kidney endpoint [hazard ratio (HR) 1.53 (95% CI 1.05–2.23), P = 0.03]. However, this association lost significance after adjustment for age and sex and remained unassociated after adjustment for additional confounders [final model: HR 0.80 (95% CI 0.50–1.29), P = 0.4].

Conclusions

These data do not show that thiazide diuretics have a detrimental effect on the rate of disease progression in ADPKD and suggest that these drugs can be prescribed as second-line antihypertensives.
Youth and Young Adult Convenience Store Behaviors: Findings From Intercept Surveys
Authors: King Jessica L , Wagoner Kimberly G , Reboussin Beth A , Sutfin Erin L
Published: May 2020

Introduction

To inform tobacco policy and prevention efforts, we examined youth and young adult behaviors at gas-station-convenience stores and whether these behaviors varied by demographics or tobacco use.

Aims and Methods

Between June and July 2017, we conducted 990 intercept surveys at convenience stores in North Carolina among 16- to 25-year olds who were susceptible to or used tobacco. We used logistic regression to examine whether demographics or tobacco use predicted pumping gas, entering the store, or purchasing tobacco, gas, food, lottery tickets, or other items inside the store.

Results

Most participants (85.3%) reported ever using tobacco. Most visited that store at least once per week (40.3%) or once within the past month (41.2%). Just over half (55.0%) reported pumping gas at the store. Of those who went or planned to go inside (68.8%), 43.2% purchased food, 39.2% purchased gas, 33.1% purchased tobacco, and 6.8% purchased lottery tickets. Those who were aged 21–25, visited the store two to three times a week, and went inside already were more likely to purchase tobacco (all p < .05). Past 30-day cigarette, cigar, smokeless, and other tobacco uses were positively associated with purchasing tobacco (all p < .05).

Conclusions

Our sample of young people who were susceptible to or ever used tobacco regularly visited gas-station-convenience stores, and one-third purchased or planned to purchase tobacco during their visit. Convenience stores appear to be an important access point for young people. Practitioners and policy makers should consider a comprehensive set of strategies to reduce access among youth and young adults.

Implications

We conducted 990 intercept surveys among youth and young adults at gas-station-convenience stores. Among our sample of those who had ever used tobacco or were susceptible to use, most visited the store frequently and one-third purchased tobacco, particularly those who used cigarettes and cigars. Tobacco companies heavily market in convenience stores, and our results show tobacco is a product often purchased by susceptible young adults. Practitioners and policy makers should consider prioritizing efforts at convenience stores to reduce product purchase and use.
Comparative Safety of Smoking Cessation Pharmacotherapies During a Government-Sponsored Reimbursement Program
Authors: Carney Greg , Maclure Malcolm , Malfair Suzanne , Bassett Ken , Wright James M , Dormuth Colin R
Published: May 2020

Introduction

The British Columbia Ministry of Health launched a Smoking Cessation Program on September 30, 2011, providing financial coverage for smoking cessation pharmacotherapies. Although pharmacotherapies have been shown to have a moderate short-term benefit as a quitting aid, substantial cardiovascular and neuropsychiatric safety concerns have been identified in adverse-reporting databases, leading to prescription label warnings by Health Canada and the U.S. Food and Drug Administration. However, recent studies indicate these warnings may be without merit. This study examined the comparative safety of medications commonly used to aid smoking cessation.

Aims and Methods

Population-based retrospective cohort study using B.C. administrative data to assess the relative safety between varenicline, bupropion, and nicotine replacement therapies (NRTs). The primary outcome was a composite of cardiovascular hospitalizations. Secondary outcomes included mortality, a composite of neuropsychiatric hospitalizations, and individual components of the primary outcome. Statistical analysis used propensity score-adjusted log-binomial regression models. A sensitivity analysis excluded patients with a history of cardiovascular disease.

Results

The study included 116 442 participants. Compared with NRT, varenicline was associated with a 10% 1-year relative risk decrease of cardiovascular hospitalization (adjusted risk ratio [RR] = 0.90, 95% confidence interval (CI): 0.82 to 1.00), a 20% 1-year relative risk decrease of neuropsychiatric hospitalization (RR: 0.80, CI: 0.7 to 0.89), and a 19% 1-year relative risk decrease of mortality (RR: 0.81, CI: 0.71 to 0.93). We found no significant association between NRT and bupropion for cardiovascular hospitalizations, neuropsychiatric hospitalizations, or mortality.

Conclusions

Compared with NRT, varenicline is associated with fewer serious adverse events and bupropion the same number of serious adverse events.

Implications

This study addresses the need for comparative safety evidence in a real-world setting of varenicline and bupropion against an active comparator. Compared with NRT, varenicline was associated with a decreased risk of mortality, serious cardiovascular events, and neuropsychiatric events during the treatment, or shortly after the treatment, in the general population of adults seeking pharmacotherapy to aid smoking cessation. These results provide support for the removal of the varenicline boxed warning for neuropsychiatric events and add substantively to the cardiovascular safety findings of previous observational studies and randomized clinical trials.
Cell-derived biomimetic nanoparticles as a novel drug delivery system for atherosclerosis: predecessors and perspectives
Authors: Yang Long , Zang Guangchao , Li Jingwen , Li Xinyue , Li Yuanzhu , Zhao Yinping
Published: May 2020

Atherosclerosis is a key mechanism underlying the pathogenesis of cardiovascular disease, which is associated with high morbidity and mortality. In the field of precision medicine for the treatment of atherosclerosis, nanoparticle (NP)-mediated drug delivery systems have great potential, owing to their ability to release treatment locally. Cell-derived biomimetic NPs have attracted extensive attention at present due to their excellent targeting to atherosclerotic inflammatory sites, low immunogenicity and long blood circulation time. Here, we review the utility of cell-derived biomimetic NPs, including whole cells, cell membranes and extracellular vesicles, in the treatment of atherosclerosis.
Methotrexate and risk of interstitial lung disease and respiratory failure in rheumatoid arthritis: a nationwide population-based study
Authors: Ibfelt Else Helene , Jacobsen Rikke Kart , Kopp Tine Iskov , Cordtz René Lindholm , Jakobsen Anna Svarre , Seersholm Niels , Shaker Saher Burhan , Dreyer Lene
Published: May 2020

Objectives

MTX is the most commonly recommended DMARD for first-line treatment of RA, however, it has been hypothesized to cause lung disease as an adverse effect. We investigated the risk of interstitial lung disease (ILD) and acute and chronic respiratory failure in persons with RA treated with MTX and other medications.

Methods

From the Danish National Patient Register (NPR) and the DANBIO register for rheumatic diseases, we retrieved data on 30 512 persons with RA registered in 1997–2015. Information on ILD and respiratory failure was obtained from the NPR. Information on age and sex for all Danish citizens was obtained from the Danish Civil Registration System. MTX and other medication purchases were retrieved from the Danish Prescription Registry. Associations between MTX and lung disease outcomes were analysed in Cox regression models with adjustment for age, calendar time, sex and other medications. Standardized incidence ratios (SIRs) of lung disease were calculated to compare the RA population with the general population.

Results

There was no increased risk of lung disease with MTX treatment [one or more purchases compared with no purchases; HR 1.00 (95% CI 0.78, 1.27) for ILD and 0.54 (95% CI 0.43, 0.67) for respiratory failure] at the 5 year follow-up. The SIR was three to four times higher for ILD in MTX-treated persons with RA, but similar to the whole RA population compared with the background population.

Conclusion

Persons with RA had an increased risk of ILD compared with the general population, but there was no further increased risk associated with MTX treatment.