bluuebunny/crossref_metadata_2025 huggingface dataset:
Can the Implicit Association Test Serve as a Valid Measure of Automatic Cognition? A Response to Schimmack (2021)
Authors: Kurdi Benedek , Ratliff Kate A. , Cunningham William A.
Published: May 2020

Much of human thought, feeling, and behavior unfolds automatically. Indirect measures of cognition capture such processes by observing responding under corresponding conditions (e.g., lack of intention or control). The Implicit Association Test (IAT) is one such measure. The IAT indexes the strength of association between categories such as “planes” and “trains” and attributes such as “fast” and “slow” by comparing response latencies across two sorting tasks (planes–fast/trains–slow vs. trains–fast/planes–slow). Relying on a reanalysis of multitrait–multimethod (MTMM) studies, Schimmack (this issue, p. 396) argues that the IAT and direct measures of cognition, for example, Likert scales, can serve as indicators of the same latent construct, thereby purportedly undermining the validity of the IAT as a measure of individual differences in automatic cognition. Here we note the compatibility of Schimmack’s empirical findings with a range of existing theoretical perspectives and the importance of considering evidence beyond MTMM approaches to establishing construct validity. Depending on the nature of the study, different standards of validity may apply to each use of the IAT; however, the evidence presented by Schimmack is easily reconcilable with the potential of the IAT to serve as a valid measure of automatic processes in human cognition, including in individual-difference contexts.
Examining the roles of coaching experience and coach training on coaches’ perceived life skills teaching
Authors: Kramers Sara , Turgeon Stéphanie , Bean Corliss , Sabourin Camille , Camiré Martin
Published: May 2020

The present study examined the roles of coaching experience and coach training on coaches’ perceived life skills teaching. Canadian high school sport coaches ( N =  1356) completed a demographic questionnaire and the Coaching life skills in sport questionnaire. Results suggested that coaches with more experience perceived themselves to discuss and practice life skills and transfer to a greater extent than coaches with less experience. No significant differences were observed based on whether coaches completed coach training, and the interaction effect between coaching experience and coach training was non-significant. Implications for coach education programs are discussed regarding training coaches to explicitly teach life skills through sport.
Mechanical character of lower limb for table tennis cross step maneuver
Authors: Shao Shirui , Yu Changxiao , Song Yang , Baker Julien S , Ugbolue Ukadike C , Lanzoni Ivan Malagoli , Gu Yaodong
Published: May 2020

The agile footwork is a basic but important skill, how to efficiently grasp and improve its performance has always interested coaches and athletes, beginners particularly. The purpose of this study was to investigate the differences in kinetics and kinematics of the cross step between professional athletes and novice athletes using the Oxford foot model. Twenty-two male participants (professional athletes, 11; novice athletes, 11) with dominant right feet participated in the table tennis cross step test. A Vicon motion analysis system and a Novel Pedar insole plantar pressure measurement system were used to record kinematic and kinetic data, respectively. Professional athletes showed significantly smaller forefoot plantarflexion and abduction, but larger hallux dorsiflexion at the cross step ending. In addition, they also showed significantly larger forefoot dorsiflexion and adduction but smaller forefoot eversion as well as rearfoot inversion than novice athletes at the forward-end of the step. In the entire motion, professional athletes performed significantly smaller joints range of motion, especially the hindfoot with respect to tibia angles. Concerning plantar relative load, professional athletes were significantly greater than that of novice athletes in the other toes, lateral forefoot and rear foot. Professional athletes possessed higher footwork agility and greater foot motor technique. The findings on the internal mechanisms of the cross step could help coaches and novice athletes understand the mechanical efficiencies in stroke finishing leading to improvements in performance.
Cartilage and extensor tendon defects after headless compression screw fixation of phalangeal and metacarpal fractures
Authors: Urbanschitz Lukas , Dreu Manuel , Wagner Julia , Kaufmann Reinhard , Jeserschek Julian M. , Borbas Paul
Published: May 2020

Osteosynthesis of metacarpal and phalangeal fractures with headless compression screws leads to a defect in the articular surface and possibly damage to the extensor tendons. This study aimed to quantify the articular surface defect and extensor tendon injuries after implant placement in cadaveric hands. Defect size was assessed with computed tomography. Extensor tendon injuries were assessed by direct visualization and measurement after dissection. In the middle phalanx, the defect size in relation to the joint surface was significantly smaller after anterograde screw placement when compared with retrograde placement. Also, a mini-open approach was found to cause significantly less tendon injury than a percutaneous approach, but there was no difference in tendon damage between retrograde and antegrade screw insertion into the middle phalanx.
Pain-related beliefs are associated with arm function in persons with frozen shoulder
Authors: De Baets L , Matheve T , Traxler J , Vlaeyen JWS , Timmermans A
Published: May 2020

Background

Frozen shoulder is a painful glenohumeral joint condition. Pain-related beliefs are recognized drivers of function in musculoskeletal conditions. This cross-sectional study investigates associations between pain-related beliefs and arm function in frozen shoulder.

Methods

Pain intensity, arm function (Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH)), pain catastrophizing (Pain Catastrophizing Scale (PCS)), pain-related fear (Tampa Scale for Kinesiophobia (TSK-11)) and pain self-efficacy (Pain Self-Efficacy Questionnaire (PSEQ)) were administered in 85 persons with frozen shoulder. Correlation analyses assessed associations between pain-related beliefs and arm function. Regression analysis calculated the explained variance in arm function by pain-related beliefs.

Results

Pain-related fear, pain catastrophizing and pain self-efficacy were significantly associated with arm function (r = 0.51; r = 0.45 and r = −0.69, all p < .0001, respectively). Thirty-one percent of variance in arm function was explained by control variables, with pain intensity being the only significant one. After adding TSK-11, PCS and PSEQ scores to the model, 26% extra variance in arm function was explained, with significant contributions of pain intensity, pain-related fear and pain self-efficacy (R2 = 0.57).

Conclusions

Attention should be paid towards the negative effect of pain-related fear on outcomes in frozen shoulder and towards building one’s pain self-efficacy given its protective value in pain management.
Individualizing Inpatient Diabetes Management During the Coronavirus Disease 2019 Pandemic
Authors: Pasquel Francisco J. , Umpierrez Guillermo E.
Published: May 2020

Diabetes is associated with poor clinical outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19). During this pandemic, many hospitals have already become overwhelmed around the world and are rapidly entering crisis mode. While there are global efforts to boost personal protective equipment (PPE) production, many centers are improvising care strategies, including the implementation of technology to prevent healthcare workers’ exposures and reduce the waste of invaluable PPE. Not optimizing glycemic control due to clinical inertia driven by fear or lack of supplies may lead to poor outcomes in patients with diabetes and COVID-19. Individualized care strategies, novel therapeutic regimens, and the use of diabetes technology may reduce these barriers. However, systematic evaluation of these changes in care is necessary to evaluate both patient- and community-centered outcomes.
A Retrospective Radiographic Evaluation of a Modified Method of Lateral Column Lengthening
Authors: Wapner Keith , Freeland Erik , Kirwan Gregory , Baldwin Keith
Published: May 2020

Background: Lateral column lengthening (LCL) is a commonly performed procedure for patients with stage II adult-acquired flatfoot deformity (AAFD) to correct forefoot abduction. This procedure is frequently completed concomitantly with both soft-tissue and bony procedures, including a medial slide calcaneal osteotomy to further reduce hindfoot valgus. The purpose of this study is to investigate and identify the radiographic outcomes of a modified step-cut LCL utilized as an alternative approach for correction of stage II AAFD. Methods: A retrospective radiographic review was performed on 15 feet in 14 patients who underwent correction of stage II AAFD using a step-cut LCL between August 2009 and January 2012. Two independent examiners utilizing 6 radiographic parameters evaluated preoperative and postoperative weight-bearing radiographs of the foot. Results: At a mean follow-up of 13.4 (range 12-16) weeks, weight-bearing radiographs demonstrated a significant median decrease in the lateral talometatarsal angle of 14.4° (P < .001), lateral talocalcaneal angle of 7° (P < .001), anteroposterior talometatarsal angle of 14.5° (P < .001), anteroposterior talocalcaneal angle of 5.5° (P < .001), and talonavicular coverage angle of 26.5° (P < .001). Additionally, a significant median increase in calcaneal pitch of 8.5° (P < .001) was noted. Conclusion: This study demonstrates statistically significant improvement of radiographic outcomes with use of a modified step-cut LCL as an alternative approach for correction of stage II AAFD.

Levels of Evidence: Level IV: Retrospective case series
Assessing the Permanence of Land-Use Change Induced by Payments for Environmental Services: Evidence From Nicaragua
Authors: Pagiola Stefano , Honey-Rosés Jordi , Freire-González Jaume
Published: May 2020

Gains achieved by conservation interventions such as payments for environmental services (PES) may be lost upon termination of the program, a problem known as permanence. However, there have been few efforts to evaluate the permanence of conservation results. This article examines the permanence of land-use changes induced by a short-term PES program implemented between 2003 and 2008 in Matiguás-Río Blanco, Nicaragua. Under this program, PES had induced substantial adoption of silvopastoral practices. To assess the long-term permanence of these changes, participants were resurveyed in 2012, 4 years after the last payment was made. We find that the land-use changes that had been induced by PES were broadly sustained in intervening years, with minor differences across specific practices and subgroups of participants. The patterns of change in the period after the PES program were completed to help us understand the reasons for the program’s success and rule out alternative explanations for the program’s success. Our results suggest that, at least in the case of productive land uses such as silvopastoral practices, PES programs can be effective at encouraging land owners to adopt environmentally beneficial practices and that the benefits will persist after payments cease.
Improving order processes with information technology: McDonald’s case
Authors: Akcam Bahadir K
Published: May 2020

This case is designed to explore the impact of information technology on business processes. The case starts with a description of a customer’s new technology experience at a McDonald’s restaurant. McDonald’s introduced multiple technologies in recent years as part of its strategic growth plan. The fast-food company is improving its business processes, mainly the order process, with new technologies to provide customer convenience. Such changes are critical to staying successful in the highly competitive fast-food industry. Self-order kiosks, the mobile order and pay app, and the Uber Eats app are three major technologies which have changed the order processes at McDonald’s. Students explore how these technologies change the order process and describe the impact of these technology initiatives at McDonald’s.
Junior doctors’ aspirations for careers in ophthalmology: 40 years of surveys of UK medical graduates
Authors: Lambert Trevor W , Barat Atena , Goldacre Michael J
Published: May 2020

Objective

Using data from 40 years of national surveys of UK medical graduates, we report on ophthalmology as a career choice.

Design, setting, and participants

Self-administered questionnaire surveys of all graduates from all UK medical schools in selected years of qualification between 1974 and 2015.

Main outcome measures

Career specialty preferences of doctors one, three, and five years after graduation; career specialty destinations 10 years after graduation.

Results

One year after graduation, ophthalmology was the first career preference of 1.6% of the qualifiers of 1974–83, 2.2% of 1993–2002, and 1.8% of 2005–15. The corresponding percentages three years after graduation were 1.5, 1.8, and 1.2%. Men were more likely than women to choose ophthalmology: among graduates of 2005–15, 2.4% of men and 1.4% of women did so at one year, as did 1.7% of men and 0.7% of women at five years. Seventy per cent of doctors practising as ophthalmologists 10 years after qualification had told us in their first post-qualification year that ophthalmology was their first choice of career.

Conclusions

There has been no systematic change in recent years in the proportion of recent medical graduates intending to have a career in ophthalmology when surveyed one year after graduation. However, the proportion at three and five years after graduation was lower than that at year 1. Suggestions for maintaining interest in the specialty include improved career advice, greater early clinical exposure to ophthalmology, and improved access to flexible training. Most practising ophthalmologists had made early decisions that this was their intended career.
Blood sampled from existing peripheral IV cannulae yields results equivalent to venepuncture: a systematic review
Authors: Lesser Finnian D , Lanham David A , Davis Daniel
Published: May 2020

Summary

Objectives

To establish whether blood samples taken from used peripheral intravenous cannulae are clinically interchangeable with venepuncture.

Design

Systematic review. PubMed, Web of Science and Embase were searched for relevant trials.

Setting

Trials which compared blood samples from used peripheral intravenous cannulae to venepuncture and provided limits of agreement or data which allowed calculation of limits of agreement.

Participants

Seven trials with 746 participants. Blood tests included 13 commonly ordered biochemistry, haematology and blood gas measurements.

Main outcome measures

95% limits of agreement. Data were pooled using inverse variance weighting and compared to a clinically acceptable range estimated by expert opinion from previous trials.

Results

Limits of agreement for blood samples from used peripheral intravenous cannulae were within the clinically acceptable range for sodium, chloride, urea, creatinine and haematology samples. Limits of agreement for potassium were ±0.47 mmol/L which exceeded the clinically acceptable range. Peripheral intravenous cannula samples for blood gas analysis gave limits of agreement which far exceeded the clinically acceptable range.

Conclusions

Blood sampling from used peripheral intravenous cannulae is a reasonable clinical practice for haematology and biochemistry samples. Potassium samples from used peripheral intravenous cannulae can be used in situations where error up to ±0.47 mmol/L is acceptable. Peripheral intravenous cannula samples should not be used for blood gas analysis.
An ecological study of publicly funded elective hip arthroplasties in Brazil and Scotland: do access inequalities reinforce the inverse care law?
Authors: Filippon Jonathan , Bremner Stephen , Giovanella Ligia , Pollock Allyson
Published: May 2020

Objectives

To compare elective hip arthroplasty rates funded by the public sector in Brazil and Scotland.

Design

Ecological study, 2009–13, of crude and directly standardised rates of elective primary hip arthroplasty rates (per 100,000) funded by the public sector at national and regional level for age (30 + years) and gender in Brazil and Scotland.

Setting

National Health Service Scotland and Unified Health System in Brazil.

Participants

Over 30 s who had undergone an elective hip arthroplasty funded by the public sector.

Main outcome measures

Publicly funded standardised elective hip arthroplasty rates in Brazil and Scotland.

Results

Between 2009 and 2013, there was a seven-fold difference in treatment rates between Brazil and Scotland, and an eight-fold regional difference in Brazil; Brazil (7.8–8.3/100,000, increase of 0.5 per 100,000, 95% confidence interval (CI) (0.3, 0.7) from 2009/10 to 2012/13) and Scotland (from 61.1 to 57.7/100,000, decrease of 3.4 per 100,000, 95% confidence interval (1.4, 5.8) per 100,000); a two-fold difference in number of public beds per head of population (Brazil 158.3/100,000 vs. Scotland 305.1/100,000) and general medical workforce (Brazil 198.8/100,000 vs. Scotland 327.4/100,000); numbers of orthopaedic surgeons per head of population in the two countries were similar in 2013 (Brazil 5.2/100,000 vs. Scotland 4.3/100,000).

Conclusion

Although the ‘inverse care law’ is seen in both countries, access to publicly funded hip arthroplasties in Brazil is worse than in Scotland; the distribution of specialists and higher treatment rates in Brazil is highly skewed towards wealthier areas, perpetuating historical regional inequalities.
Interview with MK Ajay, Executive Vice President of Human Resources, Colgate-Palmolive (India)
Authors: Thite Mohan
Published: May 2020

Colgate-Palmolive is a well-known American multinational corporation. It is well regarded as a very reputable, ethical, admired and sustainable company that values employee diversity. In this interview with the Head of HR of Colgate India, we can find some unique features in its management team, style and organisational culture. The interview explores the alignment and dynamics between business and HR strategies, long-term sustainable perspective on leadership at all levels, and building harmony in industrial relations.
Maternal microchimerism protects hemophilia A patients from inhibitor development
Authors: Lu Yeling , Chen Zhenping , Dai Jing , Wu Xi , Gu Hao , Li Zekun , Li Jian , Ding Qiulan , Wu Wenman , Wu Runhui , Wang Xuefeng
Published: May 2020

Key Points

Deleterious F8 mutations do not necessarily lead to the incidence of inhibitors in hemophilia A patients receiving replacement therapy. Maternal chimeric cells migrated into a fetus with hemophilia A during pregnancy could induce tolerance toward FVIII.
The SP1-12LOX axis promotes chemoresistance and metastasis of ovarian cancer
Authors: Zhang Qi , Yan Guifang , Lei Juan , Chen Yu , Wang Ting , Gong Juan , Zhou Yong , Zhao Huakan , Chen Hao , Zhou Yu , Wu Lei , Zhang Jiangang , Zhang Xiao , Wang Jingchun , Li Yongsheng
Published: May 2020

Background

Ovarian cancer is the most lethal gynecologic cancer. Chemoresistance, especially platinum-resistance, is closely related to metastasis of ovarian cancer, however, the molecular basis by which links chemoresistance and metastasis remains vague. Disordered arachidonic acid (AA) metabolism has been shown to play an important role in the advanced ovarian cancer. This study aimed to explore the underlying mechanism involving eicosanoid metabolism that controlling chemoresistance and metastasis of ovarian cancer.

Methods

Cisplatin (DDP)-resistant SKOV3 (SKOV3-R) cells were constantly induced. Ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was performed to determine the AA metabolism in SKOV3 and SKOV3-R cells. Half maximal inhibitory concentration (IC50) and percentage of cell viability were tested using cell counting kit 8 (CCK-8). Realtime quantitative PCR (qPCR) and immunohistochemistry (IHC) were used to evaluate indicated genes and proteins respectively. Bioinformatic analysis and chromatin immunoprecipitation (ChIP) were performed to predict and identify the co-transcription factor of interest genes. Tumor growth and metastasis in the liver were assessed with nude mice by subcutaneously injection of SKOV3-R cells.

Results

SKOV3-R cells expressed higher multidrug resistance-associated proteins (MRPs) MRP1 and MRP4. They showed enhanced metastatic ability and produced increased AA-derived eicosanoids. Mechanistically, MRPs, epithelial mesenchymal transition (EMT) markers Snail and Slug, as well as key enzymes involved in AA-metabolism including 12-lipoxygenase (12LOX) were transcribed by the mutual transcription factor SP1 which was consistently upregulated in SKOV3-R cells. Inhibition of SP1 or 12LOX sensitized SKOV3-R cells to DDP and impaired metastasis in vitro and in vivo.

Conclusion

Our results reveal that SP1-12LOX axis signaling plays a key role in DDP-resistance and metastasis, which provide a new therapeutic target for ovarian cancer.
Water-Soluble Fullerenol with Hydroxyl Group Dependence for Efficient Two-Photon Excited Photodynamic Inactivation of Infectious Microbes
Authors: Kuo Wen-Shuo , Wang Jiu-Yao , Chang Chia-Yuan , Liu Jui-Chang , Shao Yu-Ting , Lin Yen-Sung , So Edmund Cheung , Wu Ping-Ching
Published: May 2020

We successfully prepared water-soluble fullerenol [C60(OH)46] that exhibited a high singlet oxygen quantum yield and efficiently generated reactive oxygen species. Additionally, the water-soluble C60(OH)46 with a higher composition of exposed hydroxyl groups had superior two-photon stability and characteristics compared with that with a lower composition of such groups. Therefore, the prepared fullerenol can be an effective two-photon photosensitizer. The water-soluble C60(OH)46 had favorable two-photon properties. During two-photon photodynamic therapy, the water-soluble C60(OH)46 had substantial antimicrobial activity against Escherichia coli at an ultralow-energy level of 211.2 nJ pixel−1 with 800 scans and a photoexcited wavelength of 760 nm.
Exploring the recycling of bioleaching functional bacteria and sulfur substrate using the sulfur-covered biochar particles
Authors: Wu Chuncheng , Jiang Mengying , Ye Zhe , Cai Yuchen , Shen Yutao , Wang Haizhen , Lin Qi , Shen Chaofeng , Hu Baolan , Lou Liping
Published: May 2020

Background

Bioleaching has been attracting attention in the recent years as an emerging sediment heavy metal pollution remediation technology. However, the use of sulfur powder as sulfur substrate causes the problem of “post-acidification”, and the free bioleaching functional bacteria which are susceptible to environmental impact during reactor operation cannot be used efficiently for multiple rounds. These problems can be solved if the sulfur substrate and the bioleaching functional bacteria can be recycled simultaneously after bioleaching. A new kind of sulfur substrate, the laboratory-made sulfur-covered biochar particles, was used in the bioleaching experiment, compared with sulfur powder and sulfur powder mixed with the surfactant rhamnolipid.

Results

The sulfur-covered biochar particles exhibited superior bioleaching performance, including faster acidification rate, SO42− production rate and heavy metal bioleaching rate, and higher heavy metal solubilization percentage (Ni 33.76%; Cu 66.16%; Zn 65.494%), which resulted from the acceleration of bioleaching reaction by the bioleaching functional bacteria immobilized on the biochar surface. Otherwise, the sulfur-covered biochar particles could be reused in the second round, and the heavy metal solubilization percentage (Ni 32.84%, Cu 69.93%, Zn 67.17%) was comparable with that of the first round. Nevertheless, the sulfur content became the main limiting factor causing poor bioleaching performance during the third round. Sulfur mixed with the surfactant rhamnolipid did not show significant effect in promoting acidification and heavy metal solubilization due to high levels of organic matter and the impact of the low pH value.

Conclusion

The research indicated the laboratory-made sulfur-covered biochar particles could realize the dual immobilization of the bioleaching functional bacteria and the sulfur substrate to support their recycling and reuse in the second bioleaching round. In the future research, the way to maintain the reuse of the sulfur-covered biochar particles for more rounds will be explored.
Correction to: A bivariate genomic model with additive, dominance and inbreeding depression effects for sire line and three-way crossbred pigs
Authors: Christensen Ole F. , Nielsen Bjarne , Su Guosheng , Xiang Tao , Madsen Per , Ostersen Tage , Velander Ingela , Strathe Anders B.
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Identification of functional mutations associated with environmental variance of litter size in rabbits
Authors: Casto-Rebollo Cristina , Argente María José , García María Luz , Pena Romi , Ibáñez-Escriche Noelia
Published: May 2020

Background

Environmental variance (VE) is partly under genetic control and has recently been proposed as a measure of resilience. Unravelling the genetic background of the VE of complex traits could help to improve resilience of livestock and stabilize their production across farming systems. The objective of this study was to identify genes and functional mutations associated with variation in VE of litter size (LS) in rabbits. To achieve this, we combined the results of a genome-wide association study (GWAS) and a whole-genome sequencing (WGS) analysis using data from two divergently selected rabbit lines for high and low VE of LS. These lines differ in terms of biomarkers of immune response and mortality. Moreover, rabbits with a lower VE of LS were found to be more resilient to infections than animals with a higher VE of LS.

Results

By using two GWAS approaches (single-marker regression and Bayesian multiple-marker regression), we identified four genomic regions associated with VE of LS, on chromosomes 3, 7, 10, and 14. We detected 38 genes in the associated genomic regions and, using WGS, we identified 129 variants in the splicing, UTR, and coding (missense and frameshift effects) regions of 16 of these 38 genes. These genes were related to the immune system, the development of sensory structures, and stress responses. All of these variants (except one) segregated in one of the rabbit lines and were absent (n = 91) or fixed in the other one (n = 37). The fixed variants were in the HDAC9, ITGB8, MIS18A, ENSOCUG00000021276 and URB1 genes. We also identified a 1-bp deletion in the 3′UTR region of the HUNK gene that was fixed in the low VE line and absent in the high VE line.

Conclusions

This is the first study that combines GWAS and WGS analyses to study the genetic basis of VE. The new candidate genes and functional mutations identified in this study suggest that the VE of LS is under the control of functions related to the immune system, stress response, and the nervous system. These findings could also explain differences in resilience between rabbits with homogeneous and heterogeneous VE of litter size.
A single amino acid substitution in aromatic hydroxylase (HpaB) of Escherichia coli alters substrate specificity of the structural isomers of hydroxyphenylacetate
Authors: Kim Hanseol , Kim Sinyeon , Kim Dohyeon , Yoon Sung Ho
Published: May 2020

Background

A broad range of aromatic compounds can be degraded by enteric bacteria, and hydroxyphenylacetic acid (HPA) degrading bacteria are the most widespread. Majority ofEscherichia colistrains can use both the structural isomers of HPA, 3HPA and 4HPA, as the sole carbon source, which are catabolized by the same pathway whose associated enzymes are encoded byhpagene cluster. Previously, we observed thatE. coliB REL606 grew only on 4HPA, whileE. coliB BL21(DE3) grew on 3HPA as well as 4HPA.

Results

In this study, we report that a single amino acid in 4-hydroxyphenylacetate 3-hydroxylase (HpaB) ofE. colidetermines the substrate specificity of HPA isomers. Alignment of protein sequences encoded inhpagene clusters of BL21(DE3) and REL606 showed that there was a difference of only one amino acid (position 379 in HpaB) between the two, viz., Arg in BL21(DE3) and Cys in REL606. REL606 cells expressing HpaB having Arg379 could grow on 3HPA, whereas those expressing HpaB with Gly379 or Ser379 could not. Structural analysis suggested that the amino acid residue at position 379 of HpaB is located not in the active site, but in the vicinity of the 4HPA binding site, and that it plays an important role in mediating the entrance and stable binding of substrates to the active site.

Conclusions

The arginine residue at position 379 of HpaB is critical for 3HPA recognition. Information regarding the effect of amino acid residues on the substrate specificity of structural isomers can facilitate in designing hydoxylases with high catalytic efficiency and versatility.
The model cyanobacteria Anabaena sp. PCC 7120 possess an intact but partially degenerated gene cluster encoding gas vesicles
Authors: Cai Kun , Xu Bo-Ying , Jiang Yong-Liang , Wang Ying , Chen Yuxing , Zhou Cong-Zhao , Li Qiong
Published: May 2020

Background

Bacterial gas vesicles, composed of two major gas vesicle proteins and filled with gas, are a unique class of intracellular bubble-like nanostructures. They provide buoyancy for cells, and thus play an essential role in the growth and survival of aquatic and soil microbes. Moreover, the gas vesicle could be applied to multimodal and noninvasive biological imaging as a potential nanoscale contrast agent. To date, cylinder-shaped gas vesicles have been found in several strains of cyanobacteria. However, whether the functional gas vesicles could be produced in the model filamentous cyanobacteriaAnabaenasp. PCC 7120 remains controversial.

Results

In this study, we found that an intactgvpgene cluster indeed exists in the model filamentous cyanobacteriaAnabaenasp. PCC 7120. Real-time PCR assays showed that thegvpAgene is constitutively transcribed in vivo, and its expression level is upregulated at low light intensity and/or high growth temperature. Functional expression of this intactgvpgene cluster enables the recombinantEscherichia colito gain the capability of floatation in the liquid medium, thanks to the assembly of irregular gas vesicles. Furthermore, crystal structure of GvpF in combination with enzymatic activity assays of GvpN suggested that these two auxiliary proteins of gas vesicle are structurally and enzymatically conserved, respectively.

Conclusions

Our findings show that the laboratory strain of model filamentous cyanobacteriaAnabaenasp. PCC 7120 possesses an intact but partially degenerated gas vesicle gene cluster, indicating that the natural isolate might be able to produce gas vesicles under some given environmental stimuli for better floatation.
The sucrose transporter MdSUT4.1 participates in the regulation of fruit sugar accumulation in apple
Authors: Peng Qian , Cai Yaming , Lai Enhui , Nakamura Masayoshi , Liao Liao , Zheng Beibei , Ogutu Collins , Cherono Sylvia , Han Yuepeng
Published: May 2020

Background

Sugar content is an important determinant of fruit sweetness, but details on the complex molecular mechanism underlying fruit sugar accumulation remain scarce. Here, we report the role of sucrose transporter (SUT) family in regulating fruit sugar accumulation in apple.

Results

Gene-tagged markers were developed to conduct candidate gene-based association study, and an SUT4 member MdSUT4.1 was found to be significantly associated with fruit sugar accumulation. MdSUT4.1 encodes a tonoplast localized protein and its expression level had a negative correlation with fruit sugar content. Overexpression of MdSUT4.1 in strawberry and apple callus had an overall negative impact on sugar accumulation, suggesting that it functions to remobilize sugar out of the vacuole. In addition, MdSUT4.1 is located on chromosomal region harboring a previously reported QTL for sugar content, suggesting that it is a candidate gene for fruit sugar accumulation in apple.

Conclusions

MdSUT4.1 is involved in the regulation of fruit sugar accumulation in apple. This study is not only helpful for understanding the complex mechanism of fruit sugar accumulation, but it also provides molecular tools for genetic improvement of fruit quality in breeding programs of apple.
Genome-wide identification of the peptide transporter family in rice and analysis of the PTR expression modulation in two near-isogenic lines with different nitrogen use efficiency
Authors: Yang Xinghai , Xia Xiuzhong , Zeng Yu , Nong Baoxuan , Zhang Zongqiong , Wu Yanyan , Tian Qinglan , Zeng Weiying , Gao Ju , Zhou Weiyong , Liang Haifu , Li Danting , Deng Guofu
Published: May 2020

Background

Nitrogen (N) is a major nutrient element for crop growth. In plants, the members of the peptide transporter (PTR) gene family may involve in nitrate uptake and transport. Here, we identified PTR gene family in rice and analyzed their expression profile in near-isogenic lines.

Results

We identified 96, 85 and 78 PTR genes in Nipponbare, R498 and Oryza glaberrima, and the phylogenetic trees were similar in Asian cultivated rice and African cultivated rice. The number of PTR genes was higher in peanut (125) and soybean (127). The 521 PTR genes in rice, maize, sorghum, peanut, soybean and Arabidopsis could be classified into 4 groups, and their distribution was different between monocots and dicots. In Nipponbare genome, the 25 PTR genes were distributed in 5 segmental duplication regions on chromosome 1, 2, 3, 4, 5, 7, 8, 9, and 10. The PTR genes in rice have 0–11 introns and 1–12 exons, and 16 of them have the NPF (NRT1/PTR family) domain. The results of RNA-seq showed that the number of differentially expressed genes (DEGs) between NIL15 and NIL19 at three stages were 928, 1467, and 1586, respectively. Under low N conditions, the number of differentially expressed PTR genes increased significantly. The RNA-seq data was analyzed using WGCNA to predict the potential interaction between genes. We classified the genes with similar expression pattern into one module, and obtained 25 target modules. Among these modules, three modules may be involved in rice N uptake and utilization, especially the brown module, in which hub genes were annotated as protein kinase that may regulate rice N metabolism.

Conclusions

In this study, we comprehensively analyzed the PTR gene family in rice. 96 PTR genes were identified in Nippobare genome and 25 of them were located on five large segmental duplication regions. The Ka/Ks ratio indicated that many PTR genes had undergone positive selection. The RNA-seq results showed that many PTR genes were involved in rice nitrogen use efficiency (NUE), and protein kinases might play an important role in this process. These results provide a fundamental basis to improve the rice NUE via molecular breeding.
Prognostic values of the SYNTAX score II and the erythrocyte sedimentation rate on long-term clinical outcomes in STEMI patients with multivessel disease: a retrospective cohort study
Authors: Li Chuang , Zhang Qian , Wang Qianhui , Zhong Jiuchang , Wang Lefeng , Li Kuibao , Yang Xinchun
Published: May 2020

Background

There is a paucity of evidence on the combination of the SYNTAX score II (SSII) and erythrocyte sedimentation rate (ESR) in assessing the long-term prognosis of patients with ST-elevated myocardial infarction (STEMI) and multivessel disease. The objective of this study was to investigate whether the ESR could enhance the predictive value of SSII on the long-term prognosis of STEMI patients.

Methods

A retrospective cohort study involving 483 STEMI and multivessel disease subjects receiving primary percutaneous coronary intervention was conducted. Major adverse cardiovascular events (MACE) included cardiovascular death, acute heart failure, recurrent myocardial infarction, revascularization, and nonfatal stroke. The predicted values of different models were estimated by a likelihood ratio test, Akaike’s information criteria (AIC), receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

Results

During the follow-up period of up to 52 months, both the SSII and ESR were independently associated with MACE (hazard ratio [HR] = 1.032, p < 0.001; and HR = 1.021, p < 0.001, respectively). The likelihood test indicated that ESR could improve the prognostic model containing SSII (p < 0.001), while the combined model of SSII and ESR attained a lower AIC (p < 0.001). The area under the ROC curve of the combined model containing SSII and ESR increased by 0.05 (p = 0.04) compared to that of the model with SSII alone. The net reclassification and integrated discrimination of the SSII alone model improved significantly with ESR (NRI = 0.0319, p < 0.001; IDI = 0.0334, p < 0.001).

Conclusions

The prognostic model containing SSII, which is an independent risk factor of MACE, had a significantly enhanced predictive probability with the addition of ESR.
Baseline-adjusted proportional odds models for the quantification of treatment effects in trials with ordinal sum score outcomes
Authors: Buri Muriel , Curt Armin , Steeves John , Hothorn Torsten
Published: May 2020

Background

Sum scores of ordinal outcomes are common in randomized clinical trials. The approaches routinely employed for assessing treatment effects, such ast-tests or Wilcoxon tests, are not particularly powerful in detecting changes in relevant parameters or lack the ability to incorporate baseline information. Hence, tailored statistical methods are needed for the analysis of ordinal outcomes in clinical research.

Methods

We propose baseline-adjusted proportional odds logistic regression models to overcome previous limitations in the analysis of ordinal outcomes in randomized clinical trials. For the validation of our method, we focus on common ordinal sum score outcomes of neurological clinical trials such as the upper extremity motor score, the spinal cord independence measure, and the self-care subscore of the latter. We compare the statistical power of our models to other conventional approaches in a large simulation study of two-arm randomized clinical trials based on data from the European Multicenter Study about Spinal Cord Injury (EMSCI, ClinicalTrials.gov Identifier: NCT01571531). We also use the new method as an alternative analysis of the historical Sygen®clinical trial.

Results

The simulation study of all postulated trial settings demonstrated that the statistical power of the novel method was greater than that of conventional methods. Baseline adjustments were more suited for the analysis of the upper extremity motor score compared to the spinal cord independence measure and its self-care subscore.

Conclusions

The proposed baseline-adjusted proportional odds models allow the global treatment effect to be directly interpreted. This clear interpretation, the superior statistical power compared to the conventional analysis approaches, and the availability of open-source software support the application of this novel method for the analysis of ordinal outcomes of future clinical trials.
Adjusting for comorbidity in incidence-based DALY calculations: an individual-based modeling approach
Authors: McDonald Scott A. , Haagsma Juanita A. , Cassini Alessandro , Devleesschauwer Brecht
Published: May 2020

Background

The co-occurrence of two or more medical conditions in the same individual is not uncommon. If disability-adjusted life year (DALY) calculations are carried out for each condition separately, multimorbidity may lead to an overestimation of the morbidity component, the Years Lived with Disability (YLD). Adjusting for comorbidity may be straightforward if all symptoms have same onset and duration; however, when the comorbid health states occur at different time points, an analytical solution to the comorbidity problem becomes more complex. The aim of this study was to develop an individual-based modelling (IBM) approach to adjust incidence-based disease burden estimation for multimorbidity that allows simulating hypothetical individuals and tracking their disease history, including possible comorbidities, over time.

Methods

We demonstrated the IBM approach using an example of external comorbidity, i.e., colon cancer comorbid with healthcare-associated pneumonia (HAP) and by assuming an independent multiplicative model. First, each cumulative progression probabilities were converted to a daily transition probabilities. Second, disability weights for simultaneously experienced health states and duration in each health state were determined. Third, YLD, adjusted for comorbidity, was calculated at every time step. We simulated a cohort of 1000 colorectal cancer patients aged 65 years. Ninety-five percent uncertainty intervals around median YLD values were estimated by Monte Carlo methods.

Results

The median estimated YLD per 1000 cases (due to both cancer and HAP) adjusted for co-morbidity was 545 YLD/1000 (95% interval: 513–585). The impact of not adjusting disability weights for co-existent health states varied from minimal to small; YLD for colorectal cancer would be overestimated only slightly – by 1.6 YLD/1000 – by not adjusting for concurrent HAP. YLD for those HAP patients who have concurrent early-stage colorectal cancer would be overestimated by 2.3 YLD/1000.

Conclusions

The computation of disease burden in the presence of multimorbidity using the incidence-based DALY approach can be handled through IBM. Our approach can be extended to other, more complicated multimorbidity scenarios which are responsible for a high current global disease burden, such as tuberculosis and HIV infection.
Feasibility and evaluation of a large-scale external validation approach for patient-level prediction in an international data network: validation of models predicting stroke in female patients newly diagnosed with atrial fibrillation
Authors: Reps Jenna M. , Williams Ross D. , You Seng Chan , Falconer Thomas , Minty Evan , Callahan Alison , Ryan Patrick B. , Park Rae Woong , Lim Hong-Seok , Rijnbeek Peter
Published: May 2020

Background

To demonstrate how the Observational Healthcare Data Science and Informatics (OHDSI) collaborative network and standardization can be utilized to scale-up external validation of patient-level prediction models by enabling validation across a large number of heterogeneous observational healthcare datasets.

Methods

Five previously published prognostic models (ATRIA, CHADS2, CHADS2VASC, Q-Stroke and Framingham) that predict future risk of stroke in patients with atrial fibrillation were replicated using the OHDSI frameworks. A network study was run that enabled the five models to be externally validated across nine observational healthcare datasets spanning three countries and five independent sites.

Results

The five existing models were able to be integrated into the OHDSI framework for patient-level prediction and they obtained mean c-statistics ranging between 0.57–0.63 across the 6 databases with sufficient data to predict stroke within 1 year of initial atrial fibrillation diagnosis for females with atrial fibrillation. This was comparable with existing validation studies. The validation network study was run across nine datasets within 60 days once the models were replicated. An R package for the study was published at https://github.com/OHDSI/StudyProtocolSandbox/tree/master/ExistingStrokeRiskExternalValidation.

Conclusion

This study demonstrates the ability to scale up external validation of patient-level prediction models using a collaboration of researchers and a data standardization that enable models to be readily shared across data sites. External validation is necessary to understand the transportability or reproducibility of a prediction model, but without collaborative approaches it can take three or more years for a model to be validated by one independent researcher. In this paper we show it is possible to both scale-up and speed-up external validation by showing how validation can be done across multiple databases in less than 2 months. We recommend that researchers developing new prediction models use the OHDSI network to externally validate their models.
Evaluation of survival extrapolation in immuno-oncology using multiple pre-planned data cuts: learnings to aid in model selection
Authors: Bullement Ash , Willis Anna , Amin Amerah , Schlichting Michael , Hatswell Anthony James , Bharmal Murtuza
Published: May 2020

Background

Due to limited duration of follow up in clinical trials of cancer treatments, estimates of lifetime survival benefits are typically derived using statistical extrapolation methods. To justify the method used, a range of approaches have been proposed including statistical goodness-of-fit tests and comparing estimates against a previous data cut (i.e. interim data collected). In this study, we extend these approaches by presenting a range of extrapolations fitted to four pre-planned data cuts from the JAVELIN Merkel 200 (JM200) trial. By comparing different estimates of survival and goodness-of-fit as JM200 data mature, we undertook an iterative process of fitting and re-fitting survival models to retrospectively identify early indications of likely long-term survival.

Methods

Standard and spline-based parametric models were fitted to overall survival data from each JM200 data cut. Goodness-of-fit was determined using an assessment of the estimated hazard function, information theory-based methods and objective comparisons of estimation accuracy. Best-fitting extrapolations were compared to establish which one provided the most accurate estimation, and how statistical goodness-of-fit differed.

Results

Spline-based models provided the closest fit to the final JM200 data cut, though all extrapolation methods based on the earliest data cut underestimated the ‘true’ long-term survival (difference in restricted mean survival time [RMST] at 36 months: − 1.1 to − 0.5 months). Goodness-of-fit scores illustrated that an increasingly flexible model was favored as data matured. Given an early data cut, a more flexible model better aligned with clinical expectations could be reasonably justified using a range of metrics, including RMST and goodness-of-fit scores (which were typically within a 2-point range of the statistically ‘best-fitting’ model).

Conclusions

Survival estimates from the spline-based models are more aligned with clinical expectation and provided a better fit to the JM200 data, despite not exhibiting the definitively ‘best’ statistical goodness-of-fit. Longer-term data are required to further validate extrapolations, though this study illustrates the importance of clinical plausibility when selecting the most appropriate model. In addition, hazard-based plots and goodness-of-fit tests from multiple data cuts present useful approaches to identify when a more flexible model may be advantageous.

Trial registration

JAVELIN Merkel 200 was registered with ClinicalTrials.gov asNCT02155647on June 4, 2014.