bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgeons' preference sublobar resection for stage I NSCLC less than 3 cm
Authors: Huang Chien‐Sheng , Hsu Po‐Kuei , Chen Chun‐Ku , Yeh Yi‐Chen , Hsu Han‐Shui , Shih Chun‐Che , Huang Biing‐Shiun
Published: February 2020

Background

This study aimed to compare survival between standard lobectomy and surgeons' preference sublobar resection among patients with stage I non‐small cell lung cancer (NSCLC).

Methods

Medical records of patients undergoing pulmonary resection between 2006 and 2016 were reviewed retrospectively. Differences in disease‐free survival (DFS) and DFS‐associated factors between patients receiving lobectomy and surgeons' preference sublobar resection were analyzed after 1‐1 propensity score‐matching (n = 119 per group).

Results

In total, 1064 pathological stage I NSCLC patients were identified, including 816 (76.7%) who underwent lobectomy, 111 (10.4%) who underwent sublobar resection as a compromised procedure (medically unfit), and 137 (12.9%) who underwent surgeons' preference sublobar resection. Rates of five‐year DFS for patients undergoing lobectomy, medically unfit, and surgeons' preference sublobar resection were 88.7%, 71.0%, and 93.4%, respectively (P < 0.001). Multivariable Cox regression analysis demonstrated that radiological solid‐appearance (adjusted hazard [aHR] = 2.908, P = 0.003), PL2 invasion (aHR = 1.970, P = 0.024), and angiolymphatic invasion (aHR = 2.202, P = 0.005) were significantly associated with lower DFS after adjusting for surgeons' preference sublobar resection (aH = 1.031, P = 0.939). Subgroup analysis of all 403 solid‐dominant patients demonstrated equivalent five‐year DFS between surgeons' preference sublobar resection and lobectomy (87.7% and 84.1%, respectively, P = 0.721). Propensity‐matched analysis showed no differences in five‐year DFS in stage I NSCLC patients undergoing lobectomy or surgeons' preference sublobar resection (90.5% vs. 93.4% P = 0.510), and DFS for surgeons' preference sublobar resection remained an insignificant factor (aHR = 0.894, P = 0.834).

Conclusions

Carefully selected patients who have undergone surgeons' preference sublobar resection have comparable outcomes to those receiving lobectomy for stage I NSCLC <3 cm.

Key points

Significant findings of the study Intended sublobar resection has a good outcome. What this study adds Sublobar resection is applicable for stage I NSCLC <3 cm.
Beyond the Unit Root Question: Uncertainty and Inference
Authors: Webb Clayton , Linn Suzanna , Lebo Matthew J.
Published: February 2020

A fundamental challenge facing applied time‐series analysts is how to draw inferences about long‐run relationships (LRR) when we are uncertain whether the data contain unit roots. Unit root tests are notoriously unreliable and often leave analysts uncertain, but popular extant methods hinge on correct classification. Webb, Linn, and Lebo (WLL; 2019) develop a framework for inference based on critical value bounds for hypothesis tests on the long‐run multiplier (LRM) that eschews unit root tests and incorporates the uncertainty inherent in identifying the dynamic properties of the data into inferences about LRRs. We show how the WLL bounds procedure can be applied to any fully specified regression model to solve this fundamental challenge, extend the results of WLL by presenting a general set of critical value bounds to be used in applied work, and demonstrate the empirical relevance of the LRM bounds procedure in two applications.
The role of intra‐operative cell salvage in patient blood management for revision hip arthroplasty: a prospective cohort study
Authors: Palmer A. J. R. , Lloyd T. D. , Gibbs V. N. , Shah A. , Dhiman P. , Booth R. , Murphy M. F. , Taylor A. H. , Kendrick B. J. L. ,   collaborators
Published: February 2020

Cell salvage is an important component of blood management in patients undergoing revision hip arthroplasty surgery. However concerns regarding efficacy and patient selection remain. The aims of this study were to describe intra‐operative blood loss, cell salvage re‐infusion volumes and red blood cell transfusion rates for revision hip procedures and to identify factors associated with the ability to salvage sufficient blood intra‐operatively to permit processing and re‐infusion. Data were collected from a prospective cohort of 664 consecutive patients undergoing revision hip surgery at a single tertiary centre from 31 March 2015 to 1 April 2018. Indications for revision surgery were aseptic (n = 393 (59%)) fracture (n = 160 (24%)) and infection (n = 111 (17%)). Salvaged blood was processed and re‐infused when blood loss exceeded 500 ml. Mean (SD) intra‐operative blood loss was 1038 (778) ml across all procedures. Salvaged blood was re‐infused in 505 of 664 (76%) patients. Mean (SD) re‐infusion volume was 253 (169) ml. In total, 246 of 664 (37%) patients received an allogeneic red blood cell transfusion within 72 h of surgery. Patients undergoing femoral component revision only (OR (95%CI) 0.41 (0.23–0.73)) or acetabular component revision only (0.53 (0.32–0.87)) were less likely to generate sufficient blood salvage volume for re‐infusion compared with revision of both components. Compared with aseptic indications, patients undergoing revision surgery for infection (1.87 (1.04–3.36)) or fracture (4.43 (2.30–8.55)) were more likely to generate sufficient blood salvage volume for re‐infusion. Our data suggest that cell salvage is efficacious in this population. Cases where the indication is infection or fracture and where both femoral and acetabular components are to be revised should be prioritised.
From Absolution to Action: Examining Americans’ Reactions to High‐Profile Corporate Scandals
Authors: Guckian Meaghan L. , Chapman Daniel A. , Lickel Brian , Markowitz Ezra M.
Published: February 2020

When corporations behave inappropriately, for example, by intentionally circumventing emissions regulation or jacking up the price of a life‐saving drug, assessing and assigning culpability is both natural and necessary. Such ascriptions of blame influence how consumers perceive and engage with corporations in the wake of misconduct. In a nationally representative sample of American adults, we examined how people's mental models of corporate wrongdoing influenced their awareness of and responses to a series of corporate scandals that broke between 2015 and 2017. Using a mixed effects modeling approach addressing both individual and scandal‐level variability, our results revealed that subscribing to the belief that corporate scandals are the product of the corporate culture (as opposed to the actions of a “few bad apples” within an organization) amplified people's awareness of, degree of concern about, and the probability of having taken action against transgressing corporations. The findings presented here highlight the importance of exploring consumers’ complex responses to corporate scandals, particularly for regulators and consumer advocates interested in leveraging public outcry to hold corporations responsible.
Youth perspectives on weight‐related words used by healthcare professionals: A qualitative study
Authors: Stuij Mirjam , van Maarschalkerweerd Pomme E.A. , Seidell Jaap C. , Halberstadt Jutka , Dedding Christine
Published: February 2020

Background

Although healthcare professionals often consider body weight a sensitive and difficult topic to discuss with children, a contextualized and comprehensive understanding of youth perspectives on weight‐related words used in healthcare has yet to be established. This qualitative study aims to explore perspectives of Dutch children on the terminology healthcare professionals use when discussing weight.

Methods

Fourteen interviews and one focus group discussion were held with children (age 8–16) who were in care because of their weight. A toolkit with customizable interview techniques was used in order to facilitate reflection and tailor the interview to each respondent. A narrative content analysis was conducted.

Results

Respondents attached both clear and subtle differences in meanings to (certain) weight‐related words. Their perspectives were not unanimous for any single word. Moreover, at times, respondents framed certain words in positive or negative ways or used a word they disliked to describe themselves. This illustrates that meanings of weight‐related words are not fixed but context and situation specific.

Conclusion

This study revealed that meanings children assign to weight‐related words are shaped by their experiences in the broader social context, especially at school, as well as with (previous) healthcare professionals. It pointed towards the importance of bedside manner, acquaintanceship, and support. Healthcare professionals treating children because of their body weight are advised to invest in a good patient–caregiver relationship, pay attention to children's previous (negative) social weight‐related experiences, and reflect critically on their own preconceptions about body weight and the impact these preconceptions might have on their patient–caregiver relationships.
Clinical use of a 180‐day implantable glucose sensor improves glycated haemoglobin and time in range in patients with type 1 diabetes
Authors: Irace Concetta , Cutruzzolà Antonio , Nuzzi Annamaria , Assaloni Roberta , Brunato Barbara , Pitocco Dario , Tartaglione Linda , Di Molfetta Sergio , Cignarelli Angelo , Laviola Luigi , Citro Giuseppe , Lovati Elisabetta , Gnasso Agostino , Tweden Katherine S , Kaufman Francine R
Published: February 2020

Aims

This real‐world study evaluated the changes in glycated haemoglobin (HbA1c) and continuous glucose monitoring (CGM) metrics associated with use of the implantable 180‐day Eversense CGM System (Eversense) in patients with type 1 diabetes.

Materials and methods

This was a prospective, multicentre, observational study among adult participants aged ≥18 years with type 1 diabetes across seven diabetes‐care centres in Italy who had Eversense inserted for the first time. HbA1c was measured at baseline and at 180 days. Changes in time in range [TIR (glucose 70–180 mg/dL)], time above range [TAR (glucose >180 mg/dL)], time below range [TBR (glucose <70 mg/dL)] and glycaemic variability were also assessed. Data were also analysed by previous CGM use and by mode of insulin delivery.

Results

One‐hundred patients were enrolled (mean age 36 ± 12 years, mean baseline HbA1c 7.4 ± 0.92% [57 ± 10 mmol/mol]). Fifty‐six per cent of patients were users of the continuous subcutaneous insulin infusion pump and 45% were previous users of CGM. HbA1c significantly decreased in patients after 180 days of sensor wear (−0.43% ± 0.69%, 5 ± 8 mmol/mol, P < 0.0001). As expected, CGM‐naïve patients achieved the greatest reduction in HbA1c (−0.74% ± 0.48%, 8 ± 5 mmol/mol). TIR significantly increased and TAR and mean daily sensor glucose significantly decreased while TBR did not change after 180 days of sensor wear.

Conclusions

Real‐world clinical use of the Eversense CGM System for 180 days was associated with significant improvements in HbA1c and CGM metrics among adults with type 1 diabetes. The study is registered on clinicaltrials.gov (NCT04160156).
Political budget cycles and voting within a federal country: The influence of political alignment
Authors: Garofalo Pablo , Lema Daniel , Streb Jorge M.
Published: February 2020

We study how distributive politics affects political budget cycles and voting within a federal country. Our model predicts not only that the president favors politically aligned governors with larger transfers, but also that voters favor gubernatorial candidates aligned with the expected presidential incumbent because larger transfers are expected in the future. These predictions are upheld by the data from Argentinean provinces during the 1984–2014 period. Our findings imply that political alignment can trump the selection effect of voting the most competent candidate. This can help explain in particular coattail effects when gubernatorial and presidential elections are concurrent.
Stable isotopes reveal niche segregation between native and non‐native Hoplias in a Neotropical floodplain
Authors: Alves Gustavo H. Zaia , Cionek Vivian M. , Manetta Gislaine I. , Pazianoto Laryssa H. R. , Benedito Evanilde
Published: February 2020

We investigated whether isotopic niche partitioning could mediate the coexistence between native (Hoplias sp. B) and non‐native (Hoplias mbigua) trahira in a Neotropical floodplain. We hypothesised that during the dry season both species inhabit isolated sites (i.e. lakes) and thus rely on distinct food resources to sustain their coexistence. We found evidence of trophic segregation among native and non‐native freshwater fish in the Upper Paraná River, Brazil. Even though both species rely on the same primary littoral carbon sources and present similar trophic diversity, trophic segregation was attained through larger niche amplitude and smaller isotopic niche width for the non‐native fish. Three decades after initial invasion, non‐native Hoplias have distinct foraging behaviour and do not compete for trophic resources with native trahira; this is likely due to morpho‐anatomical differences. Limited morphological similarity between these congeneric species might be the strongest factor contributing to their coexistence in the Paraná River floodplain during the dry season.
EGFL6 expression in hair follicle central isthmus is dependent on the presence of terminal Schwann cells
Authors: Wei Jiang‐Ping , Gong Yao , Zhong Hong‐Bing , Hua Wang Tim , Liao Xin‐Hua
Published: February 2020

Hair follicle central isthmus is surrounded by dense nerve endings and terminal Schwann cells (TSCs), forming a specialized sensory structure called lanceolate complexes. Extracellular matrix protein EGFL6 expressed from epidermis has been found closely associated with lanceolate complexes and important for proper alignment of nerve fibres and TSCs processes, and for proper response to light touch. However, how EGFL6 itself is specifically induced/deposited/maintained at the central isthmus remains to be elucidated. Previous reports and our results showed that nerve endings and TSCs docking at the central isthmus during hair follicle development occur before the specific depositing of EGFL6 protein. Furthermore, we found nude mice rarely maintain the lanceolate complex, and EGFL6 is lost in their aberrant hair follicle. Instead, reconstituted hair follicle in nude mice by stem cells chamber grafting assay expresses EGFL6 at the central isthmus area after hair follicle innervation. At last, long‐term but not short‐term cutaneous denervation leads to degeneration of TSCs and loss of EGFL6 expression. Together, our results demonstrate that EGFL6 expression in the central isthmus is dependent on the presence of TSCs, proposing that the interplay of epidermis and neuronal components is important for maintaining functional structure of lanceolate complexes.
Optimization of TSV interconnects and BEOL layers under annealing process through fracture evaluation
Authors: Qin F. , Zhang M. , Dai Y. , Chen P. , An T. , He H. , Zhang H. , Zheng J.
Published: February 2020

Through silicon via (TSV) is a crucial interconnection structure in 3‐D integrated circuits. However, protrusion and intrusion of TSV‐Cu caused by annealing could lead to cracking and failure of back‐end‐of‐line (BEOL) layers and TSV interconnects due to mismatch of coefficient of thermal expansion. In this paper, optimizations of TSV interconnects and BEOL layers under annealing process are investigated based on fracture evaluation. Influences of geometrical factors including the TSV geometry dimension, the distance between TSV and BEOL layers, and pitch size of Cu via on energy release rate and J‐integral are studied for TSV interconnects and BEOL layers with cracks. Effect of material properties for low k dielectrics on interfacial fracture of BEOL layers and TSV interconnects is also given. Optimized geometrical factors and optimized material properties of low k dielectrics are presented in this paper. Fracture‐based method sheds a light on emerging electronic packaging optimization.
Projecting global mariculture diversity under climate change
Authors: Oyinlola Muhammed A. , Reygondeau Gabriel , Wabnitz Colette C. C. , Cheung William W. L.
Published: February 2020

Previous studies have focused on changes in the geographical distribution of terrestrial biomes and species targeted by marine capture fisheries due to climate change impacts. Given mariculture's substantial contribution to global seafood production and its growing significance in recent decades, it is essential to evaluate the effects of climate change on mariculture and their socio‐economic consequences. Here, we projected climate change impacts on the marine aquaculture diversity for 85 of the currently most commonly farmed fish and invertebrate species in the world's coastal and/or open ocean areas. Results of ensemble projections from three Earth system models and three species distribution models show that climate change may lead to a substantial redistribution of mariculture species richness potential, with an average of 10%–40% decline in the number of species being potentially suitable to be farmed in tropical to subtropical regions. In contrast, mariculture species richness potential is projected to increase by about 40% at higher latitudes under the ‘no mitigation policy’ scenario (RCP 8.5) by the mid‐21st century. In Exclusive Economic Zones where mariculture is currently undertaken, we projected an average future decline of 1.3% and 5% in mariculture species richness potential under RCP 2.6 (‘strong mitigation’) and RCP 8.5 scenarios, respectively, by the 2050s relative to the 2000s. Our findings highlight the opportunities and challenges for climate adaptation in the mariculture sector through the redistribution of farmed species and expansion of mariculture locations. Our results can help inform adaptation planning and governance mechanisms to minimize local environmental impacts and potential conflicts with other marine and coastal sectors in the future.
LINC02499, a novel liver‐specific long non‐coding RNA with potential diagnostic and prognostic value, inhibits hepatocellular carcinoma cell proliferation, migration, and invasion
Authors: Ma Xiaoyun , Mo Meile , Tan Hui Juan Jennifer , Tan Chao , Zeng Xiaoyun , Zhang Guoqiang , Huang Dongping , Liang Jun , Liu Shun , Qiu Xiaoqiang
Published: February 2020

Aim

Liver‐specific non‐coding RNAs have been reported to play crucial roles in hepatocellular carcinoma (HCC). We investigated the possible biological performance of a novel liver‐specific long non‐coding RNA, LINC02499, in HCC.

Methods

The association between LINC02499 expression and HCC was evaluated based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and then confirmed in a HCC cohort by quantitative real‐time polymerase chain reaction. The effects of LINC02499 on HCC cells were verified by gain‐ and loss‐of‐function assays. Pathway enrichment analyses were used to explore the potential mechanism of LINC02499 in HCC.

Results

LINC02499 expression was remarkably decreased in HCC tissues compared to adjacent non‐tumor tissues based on TCGA (P < 0.001) and GEO databases (P < 0.001) and our HCC cohort (P < 0.001). Decreased LINC02499 was also significantly associated with poorer overall survival in both the TCGA database (P = 0.009) and our HCC cohort (P = 0.002). Furthermore, the receiver operating characteristic analysis indicated that LINC02499 showed a good performance in HCC diagnosis (area under the curve = 0.879, P < 0.001), and both sensitivity and specificity were 83.8%. In addition, up‐ and downregulated LINC02499 significantly impacted proliferation, migration, and invasion abilities of HCC cells in vitro. Pathway enrichment analyses revealed that the potential target genes of LINC02499 were involved in “Complement and coagulation cascades” and “Butanoate metabolism” pathways.

Conclusion

LINC02499 could be a potential novel diagnostic and prognostic biomarker for HCC patients, and it could exert a tumor suppressor role in the progression of HCC.
Effects of two yellowing process on colour, taste and nonvolatile compounds of bud yellow tea
Authors: Wei Yuming , Fang Shimao , Jin Ge , Ni Tiancheng , Hou Zhiwei , Li Tiehan , Deng Wei‐Wei , Ning Jingming
Published: February 2020

The current method for processing bud yellow tea usually results in astringent taste that is not sufficiently yellowing. Therefore, two factors in the production phase that affect tea quality were studied: number of times the tea leaves undergo the yellowing process and predrying of leaves to reduce their water content before a second yellowing process. We then evaluated the colour and nonvolatile compounds of the produced tea. Results revealed that gallated catechins and the polyphenol–amino acid ratio decreased significantly, and the colour of the tea changed from green to yellow after two yellowing processes. Predrying leaves to a lower water content resulted in the accumulation of free amino acids and soluble sugars, and an increase in the brightness and yellow colour of tea infusion. Bud yellow tea with the highest taste evaluation score and yellowness was obtained when the leave samples underwent two yellowing processes and the water content in the leaves was 40%.
DOAC plasma levels measured by chromogenic anti‐Xa assays and HPLC‐UV in apixaban‐ and rivaroxaban‐treated patients from the START‐Register
Authors: Cini Michela , Legnani Cristina , Padrini Roberto , Cosmi Benilde , Dellanoce Claudia , De Rosa Giovanni , Marcucci Rossella , Pengo Vittorio , Poli Daniela , Testa Sophie , Palareti Gualtiero
Published: February 2020

Introduction

To measure direct factor Xa inhibitor (apixaban, edoxaban, rivaroxaban) concentrations, dedicated chromogenic anti‐Xa assays are recommended as suitable methods to provide rapid drug quantification. Moreover, the high‐performance liquid chromatography with ultraviolet detection (HPLC‐UV) is reported as a reliable quantitative technique. We investigated seven anti‐Xa assays and an HPLC‐UV method for measurement of apixaban and rivaroxaban levels in patients enrolled in the START‐Register.

Methods

A total of 127 apixaban and 124 rivaroxaban samples were tested by HPLC‐UV and the following anti‐Xa assays: Biophen DiXaI and Heparin LRT (Hyphen BioMed), Berichrom and Innovance Heparin (Siemens), STA‐Liquid Anti‐Xa (Stago Diagnostics), Technochrom anti‐Xa (Technoclone), and HemosIL Liquid Anti‐Xa (Werfen). Each method was performed in one of the participating laboratories: Bologna, Cremona, Florence, and Padua.

Results

Our data confirmed the overestimation of apixaban and rivaroxaban levels by the antithrombin‐supplemented anti‐Xa method (Berichrom). Performances and reproducibility of the six anti‐Xa assays not supplemented with antithrombin and the HPLC‐UV method were good, with limits of quantification from 8‐39 ng/mL (apixaban) and 15‐33 ng/mL (rivaroxaban). The six chromogenic methods showed good concordances with the quantitative HPLC‐UV [bias: −26.9‐22.3 ng/mL (apixaban), −11.3‐18.7 ng/mL (rivaroxaban)]. Higher bias and wider range between limits of agreement were observed at higher concentrations [<100 ng/mL: bias −21.3‐4.1 ng/mL (apixaban) and −6.2‐3.8 ng/mL (rivaroxaban); >200 ng/mL: bias −42.2‐36.8 ng/mL (apixaban) and −20.1‐68.9 ng/mL (rivaroxaban)].

Conclusion

Overall, the anti‐Xa assays not supplemented with antithrombin and the HPLC‐UV method proved to be suitable for apixaban and rivaroxaban quantification.
Being an internist throughout the world – same name, different training curricula
Authors: Freire Mayka , Sopeña Bernardo , Carballo Iago , Diaz‐Peromingo José A. , Vazquez‐Agra Nestor , Gonzalez‐Quintela Arturo
Published: February 2020

In the 79 countries revised, two fundamental internal medicine (IM) training patterns were in evidence, first, only basic training needed, requiring a 3–4‐year residency period for obtaining the diploma of internist; and advanced training needed, requiring 5–7 years of study. Second, evaluation of common IM training for sub‐specialists revealed the following three patterns: dual training; core training and separate training.
Antithrombin III as predictive indicator of survival in idiopathic pulmonary fibrosis (IPF) patients treated with nintedanib: a preliminary study
Authors: Bergantini Laura , d'Alessandro Miriana , Cameli Paolo , Carleo Alfonso , Landi Claudia , Vietri Lucia , Lanzarone Nicola , Pieroni Maria , Sestini Piersante , Bargagli Elena
Published: February 2020

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease often managed with nintedanib, a tyrosine kinase inhibitor targeting several profibrotic pathways. Although clotting processes are involved in wound healing and repair in the lung, there are no data on the role of antithrombin III (ATIII) in IPF patients treated with nintedanib. A previous proteomic analysis of serum of IPF patients before and after 1 year of nintedanib treatment showed differential protein expression of ATIII.

Aims

Here we used quantitative methods to evaluate differential ATIII concentrations in IPF patients before and after 1 year of nintedanib treatment and to assess the potential of ATIII as a prognostic biomarker in IPF patients.

Methods

Serum levels of ATIII were measured by enzyme‐linked immunosorbent assay in 14 IPF patients before and after 1 year of nintedanib treatment.

Results

A statistically significant inverse correlation was found between serum ATIII concentrations and pulmonary function test parameters in all patients at baseline and follow up. Baseline serum ATIII and bronchoalveolar lavage (BAL) neutrophils proved to be reliable predictors of poor prognosis. A baseline ATIII threshold of 126.5 μg/mL discriminated survivors from non‐survivors.

Conclusions

After 12 months of antifibrotic treatment, IPF patients with high serum ATIII concentrations and high BAL neutrophil percentages had a poor prognosis and increased survival risk. The results of this preliminary study suggest that ATIII has potential as a biomarker of IPF severity and in predicting response to nintedanib therapy. As a marker, ATIII showed several advantages over BAL neutrophil percentage.
Post‐secondary students with symptoms of psychosis: A mixed‐methods systematic review
Authors: Sanderson Victoria A. , Vandyk Amanda Digel , Graham Ian D. , Lightfoot Sophie , Murawsky Mackenzie , Sikora Lindsey , Jacob Jean Daniel
Published: February 2020

Post‐secondary students are at a heightened risk of psychosis, yet little is known about this population. The aim of this study was to conduct a mixed‐methods systematic review of psychosis among post‐secondary students, including student characteristics, overall prevalence, risk factors, interventions, and their reported experiences. Procedures were modelled on the Joanna Briggs Institute approach, while PRISMA guided conduct and reporting. A librarian created a systematic search of nine databases, and quality was assessed using JBI Critical Appraisal Tools. We pooled and analysed data according to objectives and recorded data using synthesis tables and narrative summaries. 26 articles published between 2006 and 2018 are included. The average age of participants was 21 years, and most identified as female and Caucasian. The prevalence of psychosis was often measured in a way that limited comparison across studies. Risk factors associated with symptoms of psychosis included substance use, depression, and younger age. Other risk factors trending towards a relationship included racial discrimination and anxiety. Protective factors included self‐esteem and self‐concept clarity. Five interventions were studied, with mixed results, and only three studies reported on the experience of students. While five promising interventions are identified, inadequate testing and replication limit confidence in their effectiveness and there is a notable deficit in qualitative evidence exploring the experiences of these students. Integrating knowledge on risk factors, interventions, and experiences of students with psychosis will help tailor and facilitate their health care while protecting their right to education.
Hydration and reaction mechanisms on sodium silicate glass surfaces from molecular dynamics simulations with reactive force fields
Authors: Mahadevan Thiruvilla S. , Du Jincheng
Published: February 2020

Recent development of reactive force fields have enabled molecular dynamics simulations of interactions between silicate glasses and water at the atomistic scale. While multicomponent silicate glasses encompass a wide variety of compositions and properties, one common structural feature in these glasses is the combination of the network structure that is made up of silica tetrahedra linked through corner sharing interspersed with network modifiers like alkali and alkaline‐earth ions that break up the Si–O–Si linkages by forming nonbridging oxygen. In reactions with water, ion exchange between alkali ions in the glass and proton or hydronium in the solution, as well as hydrolysis reaction of the Si–O–Si linkages and subsequent silanol formation, is observed and well documented. We have used a set of recently developed reactive force field to investigate the reactions between water and the surfaces of silica and sodium silicate glasses of different compositions for reactions up to 8 nanoseconds. Our results indicate sodium leaching into water and diffusion of water molecules up to 25 Å into the glass surface. We examined the structural and compositional changes inside the glass and around the diffused ions and use these to explain the rates of silanol formation at the surface. We also observed proton transport in the glass which has an indirect influence on the silanol formation rates. While the surface of the glass was rough to start with, it undergoes further modification into a hydrated gel‐like structure in the glass for up to 5 Å in the higher alkali containing glasses. It was found that the leached sodium ions remain close to the interface and that fragments of silicate network from the surface is capable of dislodging from the bulk glass and enter the aqueous solution. These simulations thus provide insights into the formation and structure of an alteration layers commonly observed in multicomponent silicate glasses corroded in aqueous solutions.
The rapidly advancing Class 2 CRISPR‐Cas technologies: A customizable toolbox for molecular manipulations
Authors: Wang Jingyi , Zhang Chenzi , Feng Bo
Published: February 2020

The CRISPR‐Cas technologies derived from bacterial and archaeal adaptive immune systems have emerged as a series of groundbreaking nucleic acid‐guided gene editing tools, ultimately standing out among several engineered nucleases because of their high efficiency, sequence‐specific targeting, ease of programming and versatility. Facilitated by the advancement across multiple disciplines such as bioinformatics, structural biology and high‐throughput sequencing, the discoveries and engineering of various innovative CRISPR‐Cas systems are rapidly expanding the CRISPR toolbox. This is revolutionizing not only genome editing but also various other types of nucleic acid‐guided manipulations such as transcriptional control and genomic imaging. Meanwhile, the adaptation of various CRISPR strategies in multiple settings has realized numerous previously non‐existing applications, ranging from the introduction of sophisticated approaches in basic research to impactful agricultural and therapeutic applications. Here, we summarize the recent advances of CRISPR technologies and strategies, as well as their impactful applications.
Methyltransferase like 3 promotes colorectal cancer proliferation by stabilizing CCNE1 mRNA in an m6A‐dependent manner
Authors: Zhu Wei , Si Yan , Xu Jun , Lin Yu , Wang Jing‐Zi , Cao Mengda , Sun Shanwen , Ding Qiang , Zhu Lingjun , Wei Ji‐Fu
Published: February 2020

m6A modification is the most prevalent RNA modification in eukaryotes. As the critical N6‐methyladenosine (m6A) methyltransferase, the roles of methyltransferase like 3 (METTL3) in colorectal cancer (CRC) are controversial. Here, we confirmed that METTL3, a critical m6A methyltransferase, could facilitate CRC progression in vitro and in vivo. Further, we found METTL3 promoted CRC cell proliferation by methylating the m6A site in 3′‐untranslated region (UTR) of CCNE1 mRNA to stabilize it. Moreover, we found butyrate, a classical intestinal microbial metabolite, could down‐regulate the expression of METTL3 and related cyclin E1 to inhibit CRC development. METTL3 promotes CRC proliferation by stabilizing CCNE1 mRNA in an m6A‐dependent manner, representing a promising therapeutic strategy for the treatment of CRC.
Thioredoxin‐interacting protein promotes activation and inflammation of monocytes with DNA demethylation in coronary artery disease
Authors: Rong Jialing , Xu Xianqun , Xiang Yang , Yang Guohua , Ming Xinliang , He Siying , Liang Bin , Zhang Xiaokang , Zheng Fang
Published: February 2020

Numerous studies have demonstrated that thioredoxin‐interacting protein (TXNIP) expression of peripheral blood leucocytes is increased in coronary artery disease (CAD). However, the molecular mechanism of this phenomenon remained unclear. DNA methylation plays important roles in the regulation of gene expression. Therefore, we speculated there might be a close association between the expression of TXNIP and methylation. In this study, we found that compared with controls, DNA methylation at cg19693031 was decreased in CAD, while mRNA expressions of TXNIP and inflammatory factors, NLRP3, IL‐1β, IL‐18, were increased. Methylation at cg19693031 was negatively associated with TXNIP expression in the cohort, THP‐1 and macrophages/foam cells. Furthermore, Transwell assay and co‐cultured adhesion assay were performed to investigate functions of TXNIP on the migration of THP‐1 or the adhesion of THP‐1 on the surface of endothelial cells, respectively. Notably, overexpressed TXNIP promoted the migration and adhesion of THP‐1 cells and expressions of NLRP3, IL‐18 and IL‐1β. Oppositely, knock‐down TXNIP inhibited the migration and adhesion of THP‐1 and expressions of NLRP3, IL‐18. In conclusion, increased TXNIP expression, related to cg19693031 demethylation orientates monocytes towards an inflammatory status through the NLRP3 inflammasome pathway involved in the development of CAD.
Incidence, risk factors, and assessment of induration by ultrasonography after chemotherapy administration through a peripheral intravenous catheter
Authors: Abe‐Doi Mari , Murayama Ryoko , Komiyama Chieko , Sanada Hiromi
Published: February 2020

Aims

Following chemotherapy, induration may occur. This study was conducted to survey induration incidence and risk factors, and investigation for actual condition of induration.

Methods

A cohort study was conducted for survey of incidence and risk factors, and a cross‐sectional observation study was conducted to examine actual condition of induration. The sites of chemotherapy administration were recorded, and these were observed on the next treatment day. Clinical nurses judged the presence or absence of induration by palpation. The sites were observed using ultrasonography. To investigate the risk factors associated with the induration, logistic regression analysis was performed using independent variables based on univariate analysis or previous reports.

Results

In total, 69 patients were analyzed. The induration incidence was 17.4%, and three abnormal conditions were confirmed: subcutaneous edema, thrombosis, and thickening of the vessel wall. Breast cancer, non‐vesicant drug, vein diameter, and fosaprepitant use were included in the logistic regression model. Breast cancer: odds ratio (OR) 9.25; 95 CI 1.91.–44.71; non‐vesicant drug: OR 1.37; 95 CI 0.13–14.95; vein diameter: OR 0.40; 95% CI 0.16–0.97; fosaprepitant use: OR 0.16; 95% CI, 0.18–10.32.

Conclusions

The induration incidence was 17.4%. Risk factors for induration following chemotherapy administration were breast cancer and smaller vein diameter. Abnormal cases of subcutaneous tissue were confirmed, including subcutaneous edema, thrombosis, and thickening of the vessel wall. Induration may be prevented by selecting larger diameter vessels using ultrasonography when catheterizing for chemotherapy.
HAADF‐STEM image analysis for size‐selected platinum nanoclusters
Authors: XIA Y. , HARRISON P. , ORNELAS I.M. , WANG H.L. , LI Z.Y.
Published: February 2020

In this study, size‐selected platinum (Pt) nanoclusters were imaged with aberration‐corrected scanning transmission electron microscopy in high‐angle annular dark field (HAADF) mode. For image analysis, a relatively simple macro program was developed by making the use of existing ImageJ plug‐ins. The macro allows effectively for assessing criterions chosen for intensity threshold and filter blurring factors. It can extract the integrated HAADF intensity, peak intensity and projected area of the clusters. Here, the effects of magnification and objective lens defocus on nanocluster measurement were investigated. It was found that the integrated HAADF intensity of Pt clusters is a more robust sample descriptor than the peak intensity and the projected area. The macro program developed is freely available.

Lay Description

Measuring precisely the size of nanoclusters plays an important role in the investigation of nanocluster‐based material systems. Aberration‐corrected scanning transmission electron microscopy (STEM) is one of the most powerful tools to extract the size of clusters directly from their images. In this study, we developed a macro program based on existing ImageJ plug‐ins, allowing easy‐assessment of criterions chosen for image intensity threshold and filter blurring factors. It can be used to extract the integrated intensity, peak intensity, and projected area of the clusters for size determination. Using the program, we investigated the effects of magnification and objective lens defocus on measurements performed on size‐selected platinum (Pt) nanoclusters, and found that the integrated intensity of Pt clusters is a more robust sample descriptor than the peak intensity and the projected area. The macro developed allows a rapid assessment of factors affecting the accuracy with which size information can be obtained from clusters.
Mitochondrial DNA copy number is associated with all‐cause mortality and cardiovascular events in patients with peripheral arterial disease
Authors: Koller A. , Fazzini F. , Lamina C. , Rantner B. , Kollerits B. , Stadler M. , Klein‐Weigel P. , Fraedrich G. , Kronenberg F.
Published: February 2020

Background

Dysfunctional mitochondria have an influence on inflammation and increased oxidative stress due to an excessive production of reactive oxygen species. The mitochondrial DNA copy number (mtDNA‐CN) is a potential biomarker for mitochondrial dysfunction and has been associated with various diseases. However, results were partially contrasting which might have been caused by methodological difficulties to quantify mtDNA‐CN.

Objective

We aimed to investigate whether mtDNA‐CN is associated with peripheral arterial disease (PAD) as well as all‐cause mortality and cardiovascular events during seven years of follow‐up.

Methods

A total of 236 male patients with PAD from the Cardiovascular Disease in Intermittent Claudication (CAVASIC) study were compared with 249 age‐ and diabetes‐matched controls. MtDNA‐CN was measured with a well‐standardized plasmid‐normalized quantitative PCR‐based assay determining the ratio between mtDNA‐CN and nuclear DNA.

Results

Individuals in the lowest quartile of mtDNA‐CN had a twofold increased risk for PAD which, however, was no longer significant after adjusting for leukocytes and platelets. About 67 of the 236 patients had already experienced a cardiovascular event at baseline and those in the lowest mtDNA‐CN quartile had a 2.34‐fold increased risk for these events (95% CI 1.08–5.13). During follow‐up, 37 PAD patients died and 66 patients experienced a cardiovascular event. Patients in the lowest mtDNA‐CN quartile had hazard ratios of 2.66 (95% CI 1.27–5.58) for all‐cause‐mortality and 1.82 (95% CI 1.02–3.27) for cardiovascular events compared with the combined quartile 2–4 (adjusted for age, smoking, CRP, diabetes, prevalent cardiovascular disease, leukocytes and platelets).

Conclusion

This investigation supports the hypothesis of mitochondrial dysfunction in peripheral arterial disease and shows an association of low mtDNA‐CNs with all‐cause‐mortality and prevalent and incident cardiovascular disease in PAD patients with intermittent claudication.
Considerations for application of biopharmaceutics classification system in chicken: Exemplified by seven drugs classification
Authors: Liu Yang , Li Xiangxiu , Zhang Yujuan , Huang Jinhu , Wu Yucheng , Wang Liping
Published: February 2020

Biopharmaceutics Classification System (BCS) has gained broad acceptance in promoting the development of human drugs. To date, the applicability of existing human BCS criteria has not been evaluated in chickens. The objective of this study was to discuss the feasibility of BCS extrapolation between species and establish a preliminary chicken BCS by classifying seven veterinary commonly used drugs including metronidazole, amoxicillin, sulfamethoxazole, sulfadiazine, ciprofloxacin hydrochloride, doxycycline hydrochloride, and trimethoprim. Firstly, we finished the determination of physiological parameters affecting solubility in chickens, including body temperature, gastrointestinal pH, and the fluid volume in the gastrointestinal tract (GI), and the drug is considered highly soluble in chicken BCS when the highest dose strength is soluble in 20.40 ml (fed) or 6.73 ml (fasted) over the pH range of 1–8 at 41°C. Drug solubility classification was based on dose number calculation. Metronidazol and amoxicillin were classed differently under fed and fasted conditions. Secondly, we discussed the effect of ABC transporters (MDCK vs. MDCK‐chAbcb1/Abcg2) and pH (5.5 vs. 7.4) on drug permeability and classification. The drug is classified as highly permeable when its permeability is equal to or greater than metoprolol tartrate. Though ABC transporters and pH significantly affected the permeability values of drugs (p < .05), the permeability classification of the drugs has not been changed except for sulfamethoxazole. This work highlights some of the significant challenges that would be encountered in order to develop a chicken BCS, this valuable information could serve as a helpful tool during chicken drugs development and to minimize the potential risks when developing formulations.
FlhF regulates the number and configuration of periplasmic flagella in Borrelia burgdorferi
Authors: Zhang Kai , He Jun , Catalano Claudio , Guo Youzhong , Liu Jun , Li Chunhao
Published: February 2020

The Lyme disease bacterium Borrelia burgdorferi has 7–11 periplasmic flagella (PF) that arise from the cell poles and extend toward the midcell as a flat‐ribbon, which is distinct from other bacteria. FlhF, a signal recognition particle (SRP)‐like GTPase, has been found to regulate the flagellar number and polarity; however, its role in B. burgdorferi remains unknown. B. burgdorferi has an FlhF homolog (BB0270). Structural and biochemical analyses show that BB0270 has a similar structure and enzymatic activity as its counterparts from other bacteria. Genetics and cryo‐electron tomography studies reveal that deletion of BB0270 leads to mutant cells that have less PF (4 ± 2 PF per cell tip) and fail to form a flat‐ribbon, indicative of a role of BB0270 in the control of PF number and configuration. Mechanistically, we demonstrate that BB0270 localizes at the cell poles and controls the number and position of PF via regulating the flagellar protein stability and the polar localization of the MS‐ring protein FliF. Our study not only provides the detailed characterizations of BB0270 and its profound impacts on flagellar assembly, morphology and motility in B. burgdorferi, but also unveils mechanistic insights into how spirochetes control their unique flagellar patterns.
Gender Identity, Analogy and Virtue: A Response Newton and Watt
Authors: Jones David Albert
Published: February 2020

William Newton and Helen Watt have both criticised the attempt to draw an analogy between gender recognition and adoption. Newton argues that recognition of adoptive fatherhood rests on an “analogy of proportion” whereas to use the word “woman” of someone whose natal sex is male is, at most, “a weak form of analogy”. However, the definition of woman provided by Newton excludes those who are infertile and neglects the cultural dimension of gender. The case of Casimir Pulaski shows that someone could participate in many of the cultural aspects of being male, as these were expressed in his society, irrespective of the facts of his internal anatomy. Watt thinks the analogy, if modified, shows that there is an onus against transitioning. She does not regard cross-dressing or taking cross-sex hormones or use of pronouns to express gender incongruence as being intrinsically wrong but argues that transitioning is potentially misleading and can have harmful consequences. Watt's practical arguments are weak as they do not include a broad range of considerations, especially considerations about inclusion and discrimination. On the other hand, Watt's concession is significant as it implies that, at least in some circumstances, transitioning could be virtuous.
δ15N values in plants are determined by both nitrate assimilation and circulation
Authors: Cui Jing , Lamade Emmanuelle , Fourel François , Tcherkez Guillaume
Published: February 2020

Nitrogen (N) assimilation is associated with 14N/15N fractionation such that plant tissues are generally 15N‐depleted compared to source nitrate. In addition to nitrate concentration, the δ15N value in plants is also influenced by isotopic heterogeneity amongst organs and metabolites. However, our current understanding of δ15N values in nitrate is limited by the relatively small number of compound‐specific data.

We extensively measured δ15N in nitrate at different time points, in sunflower and oil palm grown at fixed nitrate concentration, with nitrate circulation being varied using potassium (K) conditions and waterlogging.

There were strong interorgan δ15N differences for contrasting situations between the two species, and a high 15N‐enrichment in root nitrate. Modelling shows that this 15N‐enrichment can be explained by nitrate circulation and compartmentalisation whereby despite a numerically small flux value, the backflow of nitrate to roots via the phloem can lead to a c. 30‰ difference between leaves and roots. Accordingly, waterlogging and low K conditions, which down‐regulate sap circulation, cause a decrease in the leaf‐to‐root isotopic difference.

Our study thus suggests that plant δ15N can be used as a natural tracer of N fluxes between organs and highlights the potential importance of δ15N of circulating phloem nitrate.