bluuebunny/crossref_metadata_2025 huggingface dataset:
GelsolinanddCryABact downstream of muscle identity genes and contribute to preventing muscle splitting and branching inDrosophila
Authors: Bertin Benjamin , Renaud Yoan , Jagla Teresa , Lavergne Guillaume , Dondi Cristiana , Da Ponte Jean-Philippe , Junion Guillaume , Jagla Krzysztof
Published: September 2019

A combinatorial code of identity transcription factors (iTFs) specifies the diversity of muscle types inDrosophila. We previously showed that two iTFs, Lms and Ap, play critical role in the identity of a subset of larval body wall muscles, the lateral transverse (LT) muscles. Intriguingly, a small portion ofapandlmsmutants displays an increased number of LT muscles, a phenotype that recalls pathological split muscle fibers in human. However, genes acting downstream of Ap and Lms to prevent these aberrant muscle feature are not known. Here, we applied a cell type specific translational profiling (TRAP) to identify gene expression signatures underlying identity of muscle subsets including the LT muscles. We found thatGelsolin(Gel) anddCryAB, both encoding actin-interacting proteins, displayed LT muscle prevailing expression positively regulated by, the LT iTFs. Loss ofdCryABfunction resulted in LTs with irregular shape and occasional branched ends also observed inapandlmsmutant contexts. In contrast, enlarged and then split LTs with a greater number of myonuclei formed inGelmutants whileGelgain of function resulted in unfused myoblasts, collectively indicating thatGelregulates LTs size and prevents splitting by limiting myoblast fusion. Thus,dCryABandGelact downstream of Lms and Ap and contribute to preventing LT muscle branching and splitting. Our findings offer first clues to still unknown mechanisms of pathological muscle splitting commonly detected in human dystrophic muscles and causing muscle weakness.
Termination of pre-mRNA splicing requires that the ATPase and RNA unwindase Prp43p acts on the catalytic snRNA U6
Authors: Toroney Rebecca , Nielsen Klaus H. , Staley Jonathan P.
Published: September 2019

The termination of pre-mRNA splicing functions to discard suboptimal substrates, thereby enhancing fidelity, and to release excised introns in a manner coupled to spliceosome disassembly, thereby allowing recycling. The mechanism of termination, including the RNA target of the DEAH-box ATPase Prp43p, remains ambiguous. We discovered a critical role for nucleotides at the 3′ end of the catalytic U6 small nuclear RNA in splicing termination. Although conserved sequence at the 3′ end is not required, 2′ hydroxyls are, paralleling requirements for Prp43p biochemical activities. Although the 3′ end of U6 is not required for recruiting Prp43p to the spliceosome, the 3′ end cross-links directly to Prp43p in an RNA-dependent manner. Our data indicate a mechanism of splicing termination in which Prp43p translocates along U6 from the 3′ end to disassemble the spliceosome and thereby release suboptimal substrates or excised introns. This mechanism reveals that the spliceosome becomes primed for termination at the same stage it becomes activated for catalysis, implying a requirement for stringent control of spliceosome activity within the cell.
Crystal structures of 3-chloro-2-nitrobenzoic acid with quinoline derivatives: 3-chloro-2-nitrobenzoic acid–5-nitroquinoline (1/1), 3-chloro-2-nitrobenzoic acid–6-nitroquinoline (1/1) and 8-hydroxyquinolinium 3-chloro-2-nitrobenzoate
Authors: Gotoh Kazuma , Ishida Hiroyuki
Published: September 2019

The structures of three compounds of 3-chloro-2-nitrobenzoic acid with 5-nitroquinoline, (I), 6-nitroquinoline, (II), and 8-hydroxyquinoline, (III), have been determined at 190 K. In each of the two isomeric compounds, (I) and (II), C7H4ClNO4·C9H6N2O2, the acid and base molecules are held together by O—H...N and C—H...O hydrogen bonds. In compound (III), C9H8NO+·C7H3ClNO4
−, an acid–base interaction involving H-atom transfer occurs and the H atom is located at the N site of the base molecule. In the crystal of (I), the hydrogen-bonded acid–base units are linked by C—H...O hydrogen bonds, forming a tape structure along the b-axis direction. Adjacent tapes, which are related by a twofold rotation axis, are linked by a third C—H...O hydrogen bond, forming wide ribbons parallel to the (\overline{1}03) plane. These ribbons are stacked via π–π interactions between the quinoline ring systems [centroid–centroid distances = 3.4935 (5)–3.7721 (6) Å], forming layers parallel to the ab plane. In the crystal of (II), the hydrogen-bonded acid–base units are also linked into a tape structure along the b-axis direction via C—H...O hydrogen bonds. Inversion-related tapes are linked by further C—H...O hydrogen bonds to form wide ribbons parallel to the (\overline{3}08) plane. The ribbons are linked by weak π–π interactions [centroid–centroid distances = 3.8016 (8)–3.9247 (9) Å], forming a three-dimensional structure. In the crystal of (III), the cations and the anions are alternately linked via N—H...O and O—H...O hydrogen bonds, forming a 21 helix running along the b-axis direction. The cations and the anions are further stacked alternately in columns along the a-axis direction via π–π interactions [centroid–centroid distances = 3.8016 (8)–3.9247 (9) Å], and the molecular chains are linked into layers parallel to the ab plane through these interactions.
Crystal structures of three hexakis(fluoroaryloxy)cyclotriphosphazenes
Authors: Yennawar Hemant P. , Hess Andrew R. , Allcock Harry R.
Published: September 2019

The syntheses and crystal structures of three cyclotriphosphazenes, all with fluorinated aryloxy side groups that generate different steric characteristics, viz. hexakis(pentafluorophenoxy)cyclotriphosphazene, N3P3(OC6F5)6, 1, hexakis[4-(trifluoromethyl)phenoxy]cyclotriphosphazene, N3P3[OC6H4(CF3)]6, 2 and hexakis[3,5-bis(trifluoromethyl)phenoxy]cyclotriphosphazene, N3P3[OC6H3(CF3)2]6
3, are reported. Specifically, each phosphorus atom bears either two pentafluorophenoxy, 4-trifluoromethylphenoxy, or 3,5-trifluoromethylphenoxy groups. The central six-membered phosphazene rings display envelope pucker conformations in each case, albeit to varying degrees. The maximum displacement of the `flap atom' from the plane through the other ring atoms [0.308 (5) Å] is seen in 1, in a molecule that is devoid of hydrogen atoms and which exhibits a `wind-swept' look with all the aromatic rings displaced in the same direction. In 3 an intramolecular C—H(aromatic)...F interaction is observed. All the –CF3 groups in 2 and 3 exhibit positional disorder over two rotated orientations in close to statistical ratios. The extended structures of 2 and 3 are consolidated by C—H...F interactions of two kinds: (a) linear chains, and (b) cyclic between molecules related by inversion centers. In both 1 and 3, one of the six substituted phenyl rings has a parallel-displaced aromatic π–π stacking interaction with its respective symmetry mate with slippage values of 2.2 Å in 1 and 1.0 Å in 3. None of the structures reported here have solvent voids that could lead to clathrate formation.
Transforming the public sector: 1998–2018
Authors: Lapsley Irvine , Miller Peter
Published: September 2019

Purpose

The purpose of this paper is to provide an evaluation of public sector research in the 1998–2018 period.

Design/methodology/approach

The paper uses the extant literature of this era to study the theorisation of, and the findings of, public sector research.

Findings

This is a vibrant field of a study in a wide range of study settings and with many interdisciplinary studies. The influence of new public management is pervasive over this period. There are numerous instances of innovations in study settings, in key findings and the approach taken by investigators.

Research limitations/implications

This is not a comprehensive review of all literature in this period.

Practical implications

This study also explored the relevance of academic research of this era to policymaking by governments.

Originality/value

This paper offers a distinctive critique of theorisation of public sector accounting research. It reveals the dominant theoretical reference points in use during this period and observes the increasing tendency for theoretical pluralism to investigate complex study settings.
Are family firms more optimistic than non-family firms?
Authors: Huang Xuan , Kang Fei
Published: September 2019

Purpose

The purpose of this study is to investigate how family ownership affects the disclosure tone of firm earnings press releases.

Design/methodology/approach

Following prior literature, this study defines family firms as those in which members of the founding families continue to hold positions in top management, to sit on the board or to be blockholders. The disclosure tone of earnings press releases is measured by the level of optimism in firms’ earnings announcements using Loughran and McDonald’s (2011) word classifications. Multivariate analysis is performed to examine the impact of family ownership on firms’ disclosure tone. Additional analysis includes controlling for different firm-level characteristics and using alternative measures of disclosure tone.

Findings

This study documents that the disclosure tone of earnings announcements is more optimistic for family firms than for non-family firms. The result implies that family owners’ large undiversified equity position in their business results in strong incentives for them to issue more positive earnings announcements to maintain high stock performance. Further analysis reveals that the results are mainly driven by family firms with founder CEOs. The results are robust to controls for corporate governance characteristics and to alternative measures of corporate disclosure tone.

Originality/value

The findings of this study contribute to the literature that examines factors associated with the determinants of the tone in firms’ earnings announcements. In addition, this study adds to the extant literature on family firms by providing useful insight into the influence of family control on corporate voluntary disclosure.
Critical success factors for maintenance of local public buildings
Authors: Hopland Arnt Ove , Kvamsdal Sturla F.
Published: September 2019

Purpose

The purpose of this paper is to investigate a survey on critical success factor for the maintenance of local public buildings and how reported score values and factor rankings depend on characteristics (contingencies) of the local governments that participated.

Design/methodology/approach

The authors use data from a large-scale survey of Norwegian local governments that covered 66 per cent of all local governments and 80 per cent of the population. The authors combine these data with contingent information from public registers on demographics, fiscal, political and geographical characteristics. The authors run regressions to determine whether contingencies affect survey results. They further study how score values vary with a key contingent factor.

Findings

The main result of this paper is that the reported importance of critical success factors is contingent on local government population levels. A comparison of importance rankings based on population quartiles shows that ranking orders change, both between quartiles and from the overall ranking, and that certain factors show systematic changes. Further, the authors find that when controlling for sampling error, groups of factors should be considered as equally important. This result holds both for the full sample ranking and for rankings within population quartiles.

Originality/value

The results of this paper have implications for all survey-based investigations of critical success factors where contingent information on respondents are available. Contingencies need to be taken into consideration, both when assessing rankings according to some criteria and when comparing actual score values.
Reviving the lost spaces under urban highways and bridges: an empirical study
Authors: Lak Azadeh , Ramezani Mina , Aghamolaei Reihaneh
Published: September 2019

Purpose

The fast development of urban movement infrastructures has created neglected urban places in cities. This study aims to provide users’ preferences for designing lost spaces that are a by-product of elevated urban highways (UHs) and bridges to develop a conceptual model for better environmental design.

Design/methodology/approach

This research is conducted by a combination of both qualitative and quantitative methods. In the first phase, to explore the citizen’s environmental preferences based on the Q-sort technique and in-depth interviews, the ideas of 50 users were considered up to data saturation. The preferences of people for designs under urban bridges were extracted by content analysis in the qualitative phase. In the quantitative phase, to validate these preferences, the extracted themes and sub-themes were examined by 144 experts in design studies using the web-based questionnaire based on the first phase outcomes. The validity of the model was confirmed by confirmatory factor analysis in SPSS22 and Lisrel software.

Findings

The findings show that users’ preferences emphasize design strategies such as safety and security, physical coherence, visibility, vitality, richness, a sense of belonging and comfort to the design of lost spaces. Overall, this study highlights an empirical study into user’s needs and expectations of lost urban spaces.

Originality/value

The findings show that users’ preferences emphasize design strategies such as safety and security, physical coherence, visibility, vitality, richness, a sense of belonging and comfort to the design of lost spaces. Overall, this study highlights an empirical study into user’s needs and expectations of lost urban spaces.
Meaning, perceptions and use of lean – a New Zealand perspective
Authors: Thornton Kim , Nath Nirmala , Hu Yuanyuan , Jia Jing
Published: September 2019

Purpose

This study aims to explore how lean and lean dimensions are perceived by senior managers in New Zealand (NZ). The authors use Searcy’s (2004) framework to establish how lean performance dimensions differ in importance in terms of sector, size and users of lean, thus, revealing the motivations and benefits of lean from the view of lean organisations.

Design/methodology/approach

Data were primarily sourced using an online survey tool. A thematic approach was used to establish an understanding of lean by NZ senior managers. An analytical hierarchy process model was used to determine if the relative importance of the lean performance dimensions is perceived differently between manufacturing and service organisations, large firms and small- and medium-sized enterprises and adopters and non-adopters of lean. The results are informed by Searcy’s (2004) framework.

Findings

The study reveals efficiency, elimination of waste, cost reduction and meeting customer demands based on secondary sources, to be the current prevalent dimensions of lean in NZ. Managers are yet to realise the importance of customer value and product quality, and the former is at the heart of the successful diffusion of lean dimensions. Customer value is beyond satisfying customer demands and needs; the focus is on how the authors can understand the customers.

Research limitations/implications

The sample size limits the generalisability of the results.

Practical implications

The study suggests that practitioners, including managers, need to incorporate customer demand and satisfaction into their lean performance dimensions to improve effectiveness. This group of actors should be instrumental in taking the lean philosophy, tools and techniques to NZ firms by hosting in-house training and seminars at regional and national levels. Furthermore, academics should incorporate lean studies as a programme/course in their respective tertiary institutions so that graduates can take this phenomenon to their workplace.

Originality/value

This study contributes to the understanding of lean within a NZ business context and provides evidence that NZ corporate managers need to incorporate customer value and product quality aspects when adopting lean.
Introduction to the Special Section: The Autonomisation of Weapons Systems: Challenges to International Relations
Authors: Bode Ingvild , Huelss Hendrik
Published: September 2019

The collection of eight articles in this special section provides insightful thinking points in the context of the political debate, the academic conversation, and the public interest in novel security technologies with autonomous features. These articles are also a call for further, empirically and theoretically informed research into the implications of AI for the international security dimension, specifically, and for societies more generally.
Globalisation and the Recent Trade Wars: Linkages and Lessons
Authors: Oramah Benedict , Dzene Richman
Published: September 2019

Anti‐globalization sentiments have risen significantly in developed economies, impacting the outcome of national elections in the US and the BREXIT referendum in the United Kingdom. It has also led to tariff escalations and trade wars, especially between the US and China. These developments run contrary to the conventional wisdom that globalization has positively Impacted the global economy and that the distribution of gains has been in favor of developed economies. This paper argues that it is the incomplete implementation of the main pillars of globalization that has created rising discontent in developed countries. Conceived as the process of integration of goods, capital, technology and labor, globalization was premised on free movement of goods and factors of production within and across countries as well on the assumption that factors of production would be perfect substitutes everywhere. The paper posits that it is the immobility of labor across and within countries that has led to the globalization‐induced dislocations in some developed economies. Across countries, artificial immigration barriers restrict labor movement while within countries, labor market rigidities and absence of perfect substitution in the labor market constrain the migration of labor from the declining to the booming sectors of the economy creating large income inequalities. Implications of the foregoing for the future of globalization and Africa’s export‐led industrialization are presented.
Would Gradual De‐Dollarization and More Financing in Local Currencies Boost Trade?
Authors: Hirschhofer Harald
Published: September 2019

The article summarizes arguments in favor of de‐nominating trade finance in local currencies. By reducing exposure to policy developments in reserve currency countries and improving the allocation of currency risk with the help of global currency risk markets will have a positive long‐term impact on stability, trade volumes, and growth.
The Efficacy of Technology‐Based Interventions for Alcohol and Illicit Drug Use Among Women of Childbearing Age: A Systematic Review and Meta‐Analysis
Authors: Hai Audrey Hang , Hammock Kyndal , Velasquez Mary M.
Published: September 2019

Background

Alcohol and illicit drug use is prevalent among women of childbearing age and may lead to higher risk for substance‐exposed pregnancy and related health consequences for both women and their offspring. Technology‐based interventions (TBIs) are increasingly used to prevent or reduce substance use among women of childbearing age. The efficacy of these approaches, however, is unclear. This review critically reviewed existing research evidence from randomized controlled trials (RCTs) on the efficacy of TBIs in preventing and reducing alcohol and illicit drug use among childbearing‐aged women.

Methods

Seven electronic databases were searched to identify eligible studies. Two reviewers independently screened studies, extracted data, and assessed risks of bias. Robust variance estimation in meta‐regression was used to estimate effect sizes and conduct moderator analyses.

Results

Fifteen RCTs including 3,488 participants were included in the systematic review. Meta‐analysis results based on 13 RCTs suggest that TBIs were efficacious relative to control conditions in preventing and reducing substance use among women of childbearing age (d = 0.19, 95% CI = 0.02, 0.35). Preliminary moderator analysis results suggest that the efficacy of TBIs might not vary by participant age, race/ethnicity, the type of technology used, or whether a virtual health assistant was used. TBIs’ efficacy in terms of specific substance use types (alcohol use and illicit drug use) or control types (inactive control and active controls) was inconclusive, due to the limited number of studies in each category.

Conclusions

This systematic review and meta‐analysis found evidence of TBIs’ efficacy in reducing alcohol and illicit drug use among women of childbearing age. Implications for future research and practice are discussed.
Event‐Level Correlates of Drinking Events Characterized by Alcohol‐Induced Blackouts
Authors: Merrill Jennifer E. , Boyle Holly K. , Jackson Kristina M. , Carey Kate B.
Published: September 2019

Background

Prior research identifies a range of potential predictors of blackouts and suggests that blackouts increase risk for additional negative consequences. However, these studies are based on epidemiological work that allows us to draw conclusions about groups of people but not within‐person processes. The present study examined within‐person, event‐level correlates of blackouts.

Methods

Ninety‐six heavy drinking college students (52% female) completed 28 days of daily reports of alcohol use and consequences, including blackouts. Thirty‐three participants reported 56 blackouts. Hierarchical linear modeling compared morning reports of drinking events on which participants did versus did not report a blackout, controlling for total drinks at the event.

Results

Blackout likelihood increased as a function of total drinks consumed and of crossing thresholds for heavy episodic drinking (4+/5+ drinks for women/men) and high‐intensity drinking (8+/10+). Participants reported a higher total number of additional negative consequences on blackout events. Specific consequences that were more likely included embarrassing oneself and hangover. Blackouts were associated with morning ratings of less positive mood and a less favorable drinking event. Motives for drinking and simultaneous use of marijuana were not associated with blackouts.

Conclusions

Event‐level findings of this study document that events leading to alcohol‐induced memory loss are associated with other adverse experiences relative to drinking events that do not result in blackout, and offer potentially motivational levers for preventive interventions.
Age‐related cataract and 10‐year mortality: the Liwan Eye Study
Authors: Zhu Zhuoting , Wang Lanhua , Scheetz Jane , He Mingguang
Published: September 2019

Purpose

To explore the association between age‐related cataract and 10‐year mortality in an adult population in urban China.

Methods

A total of 1405 participants aged 50 years or older were examined at baseline in the Guangzhou Liwan Eye Study. All participants were invited to attend a 10‐year follow‐up visit. Cataract cases were defined as either having visible lens opacity confirmed with direct ophthalmoscope under pupil dilation or previous history of cataract surgery. Visual impairment (VI) was defined as a visual acuity of 20/40 or worse in the better‐seeing eye with habitual correction if worn. Body mass index (BMI) was based on anthropometric data. A brief questionnaire regarding family income, educational attainment and medical history of systemic disease was administered. Mortality rates were compared using the log‐rank test and Cox proportional hazards regression models.

Results

Among 1405 participants examined at baseline, 957 participants (68.1%) had visible lens opacity or history of cataract surgery. After 10 years, 320 (22.8%) participants died. The 10‐year mortality rate was significantly higher in participants with cataract than in those without (30.1% versus 7.14%, log‐rank p < 0.05). After adjusting for age, gender, family income, educational attainment, BMI, history of diabetes and hypertension and presence of VI, presence of cataract predicted a nearly threefold increase in the risk of mortality (HR, 2.99; 95% CI, 1.89–4.71).

Conclusions

Our findings that age‐related cataract is a predictor for poorer survival compared to those without may imply that cataract is a biomarker of ageing and frailty.
Lung function and pulmonary vascular resistance are not associated in 6‐year‐old children born extremely preterm
Authors: Mohlkert Lilly‐Ann , Sjöberg Gunnar , Rydberg Annika , Pegelow Halvorsen Cecilia , Tufvesson Ellen , Hallberg Jenny , Domellöf Magnus , Norman Mikael
Published: September 2019

Aim

Children born preterm are at increased risk of reduced lung function. The aim was to test whether lung function was associated with pulmonary vascular resistance.

Methods

Participants were recruited from a population‐based cohort born in 2004‐2007. Lung function was assessed with spirometry after administration of a beta2‐agonist. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were determined. Estimations of pulmonary vascular resistance, arterial dimensions, right ventricular wall thickness, sphericity, and systolic (TAPSE) and diastolic functions were performed with echocardiography. Adjusted regression analyses were used to study associations.

Results

Sixty‐six children (33 boys) born at 22‐26 weeks of gestational age (birthweights 460‐1134 g) were assessed at a mean age of 6.7 years. Despite large variations in lung function with FVC z‐scores ranging from −4.6 to +2.8, there were no associations between lung function and pulmonary arterial pressure, right ventricular structure or function. Children with higher FVC z‐scores (r = .52, β = .55 mm, P = .015) and higher FEV1 z‐scores (r = .58, β = .73 mm, P = .001) exhibited larger pulmonary arteries.

Conclusion

In children born extremely preterm, lung function was not associated with pulmonary vascular resistance. Routine echocardiographic evaluation of extremely preterm children may not be indicated at age 6.5 years.
Acanthosis nigricans in childhood: A cutaneous marker that should not be underestimated, especially in obese children
Authors: Maguolo Alice , Maffeis Claudio
Published: September 2019

Aim

The occurrence of acanthosis nigricans (AN) in childhood should not be underestimated since it acts as a cutaneous marker of underlying diseases, such as insulin resistance, endocrinopathy, syndromes and malignancy. The purpose of this review was to highlight the clinical significance of AN in childhood and draw attention to its possible role as early marker of alterations in glucose metabolism in obese children.

Methods

The Cochrane Library and PubMed databases were searched for papers published in English up to April 2019. Observational studies, case reports and reviews from 1994 to 2019 were included.

Results

Most of the cases of AN are associated with obesity. The prevalence of obesity is rising worldwide and is paralleled by global increases in the prevalence of metabolic syndrome in children. Insulin resistance and AN are closely associated. Evidence indicates that AN is a useful clinical marker for the identification of obese and overweight children and adolescents with insulin resistance who are susceptible to type 2 diabetes mellitus and metabolic syndrome.

Conclusion

In clinical practice, the recognition of AN is useful for an early identification of children and adolescents, prone to the insulin‐resistant obese phenotype, who could benefit from early interventions.
Distinct age‐related patterns of overweight development to guide school healthcare interventions
Authors: Häkkänen Paula , But Anna , Ketola Eeva , Laatikainen Tiina
Published: September 2019

Aim

We aimed to identify groups of primary school children with similar overweight development, reveal age‐related patterns of overweight development in the resulting groups and analyse overweight‐related school healthcare interventions.

Methods

This retrospective longitudinal register study utilised electronic health records from six primary school years. From a random sample of 2000 sixth graders, we derived a study cohort of 508 children meeting criteria for overweight at least once during primary school. We investigated how many different groups (latent classes) of children with similar weight development would emerge by applying flexible latent class mixed models on body mass index standard deviation score. We also explored the resulting groups with respect to offered overweight‐related interventions.

Results

Per child, the data consisted in median 7 growth measurements over 5.4 years. We identified five overweight development groups for girls and four for boys. The groups converged temporarily around age 10 after which only some continued into obesity. School nurses and physicians offered overweight‐related interventions to children with obesity, less to children gaining weight or with overweight.

Conclusion

Obesity prevention might benefit from awareness of typical overweight development patterns when designing intervention studies or planning and timing multidisciplinary school health check programmes.
Exploration of 5‐(5‐nitrothiophen‐2‐yl)‐4,5‐dihydro‐1H‐pyrazoles as selective, multitargeted antimycobacterial agents
Authors: Agre Neha , Khambete Mihir , Maitra Arundhati , Gupta Antima , Munshi Tulika , Bhakta Sanjib , Degani Mariam
Published: September 2019

We report the biological evaluation of 5‐(5‐nitrothiophen‐2‐yl)‐4,5‐dihydro‐1H‐pyrazole derivatives against bacteria, eukaryotic cell lines and the assessment of their mechanisms of action to determine their prospects of being developed into potent antituberculosis agents. The compounds were evaluated for their antibacterial property against Mycobacterium tuberculosis H37Rv, multidrug‐resistant M. tuberculosis, Mycobacterium bovis BCG, Mycobacterium aurum, Escherichia coli, and Staphylococcus aureus using high‐throughput spot‐culture growth inhibition assay. They were found to be selective toward slow‐growing mycobacteria and Gram‐positive bacteria. In M. bovis BCG, they exhibited a bactericidal mode of action. Cytotoxicity was assessed in human THP‐1 and murine RAW 264.7 cell lines, and the compounds showed a lower cytotoxicity potential when compared with their antibacterial activity. They were found to be excellent whole‐cell efflux pump inhibitors of the mycobacterial surrogate M. aurum, performing better than known efflux pump inhibitor verapamil. The 5‐nitrothiophene moiety was identified for the first time as a prospective inhibitor scaffold of mycobacterial arylamine N‐acetyltransferase enzyme, which is the key enzyme in metabolizing isoniazid, a first‐line antituberculosis drug. The two aforementioned findings make the compounds potential hits in the development of adjunctive tuberculosis therapy.
Impact of type 2 diabetes on hospitalization and mortality in people with malignancy
Authors: Kiburg K. V. , Ward G. M. , Vogrin S. , Steele K. , Mulrooney E. , Loh M. , McLachlan S. A. , Sundararajan V. , MacIsaac R. J.
Published: September 2019

Aim

To compare the characteristics of and outcomes for people with malignancies with and without a co‐diagnosis of diabetes.

Methods

Emergency department and hospital discharge data from a single centre for the period between 1 January 2015 and 31 December 2017 were used to identify people with a diagnosis of a malignancy and diabetes. Multivariate Cox regression models were used to estimate the effect of diabetes on all‐cause mortality. A truncated negative binomial regression model was used to assess the impact of diabetes on length of hospital inpatient stay. Prentice–Williams–Peterson total time models were used to assess the effect of diabetes on number of emergency department re‐presentations and inpatient re‐admissions.

Results

Of 7004 people identified with malignancies, 1195 (17.1%) were also diagnosed with diabetes. A diagnosis of diabetes was associated with a greater number of inpatient re‐admissions [adjusted hazard ratio 1.13 (95% CI 1.03, 1.24)], a greater number of emergency department re‐presentations [adjusted hazard ratio 1.13 (95% CI 1.05, 1.22)] and longer length of stay [adjusted incidence rate ratio 1.14 (95% CI 1.04, 1.25)]. A co‐diagnosis of diabetes was also associated with a 48% increased risk of all‐cause mortality [adjusted hazard ratio 1.48 (95% CI 1.22–1.76)].

Conclusions

People with malignancies and diabetes had significantly more emergency department presentations, more inpatient admissions, longer length of hospital stay and higher rates of all‐cause mortality compared to people with a malignancy without diabetes.
FORWARD Study: Evaluating the Comparative Effectiveness of OnabotulinumtoxinA and Topiramate for Headache Prevention in Adults With Chronic Migraine
Authors: Rothrock John F. , Adams Aubrey Manack , Lipton Richard B. , Silberstein Stephen D. , Jo Esther , Zhao Xiang , Blumenfeld Andrew M. ,   on behalf of the FORWARD Study investigative group
Published: September 2019

Objective

To compare effectiveness of onabotulinumtoxinA and topiramate for chronic migraine (CM) prevention.

Background

The efficacy* of onabotulinumtoxinA and topiramate has been established in placebo‐controlled randomized clinical trials (*defined as the benefit of treatment under ideal conditions). The effectiveness* of the 2 preventive treatments, however, has not been established (*the benefit of treatment under real‐world conditions, representing a blend of efficacy and tolerability).

Methods

In this multicenter, randomized, parallel‐group, post‐authorization, open‐label prospective study (FORWARD; ClinicalTrials.gov, NCT02191579), we randomized adults with CM (1:1) to onabotulinumtoxinA 155 U every 12 weeks for 3 cycles or topiramate “immediate release” 50‐100 mg/day to week 36. Primary outcome measure was proportion of patients achieving ≥50% reduction in headache days (weeks 29‐32). Missing values were imputed using baseline observation carried forward (BOCF) methodology. After 12 weeks, patients initially randomized to topiramate could cross over to onabotulinumtoxinA treatment. We monitored and recorded all adverse events (AEs).

Results

We enrolled 282 patients (onabotulinumtoxinA, n = 140; topiramate, n = 142) and 148 patients completed randomized treatment (onabotulinumtoxinA, n = 120 [86%]; topiramate, n = 28 [20%]). Primary reasons for withdrawal were ineffective treatment (onabotulinumtoxinA, n = 7 [5%]; topiramate, n = 27 [19%]) and AEs (onabotulinumtoxinA, n = 5 [4%]; topiramate, n = 72 [51%]). Eighty topiramate patients crossed over to onabotulinumtoxinA.

In the BOCF analysis, a significantly higher proportion of patients randomized to onabotulinumtoxinA experienced ≥50% reduction in headache frequency compared with those randomized to topiramate (40% [56/140] vs 12% [17/142], respectively; adjusted OR, 4.9 [95% CI, 2.7‐9.1]; P < .001). OnabotulinumtoxinA was superior to topiramate in meeting secondary endpoints. In a post hoc analysis using observed data, the 50% responder rates at week 12 were 45.6% for onabotulinumtoxinA (n = 125) and 29.4% for topiramate (n = 109) (P = .015). AEs were reported by 48% (105/220) of onabotulinumtoxinA and 79% (112/142) of topiramate patients. Results were similar in those who crossed over to onabotulinumtoxinA.

Conclusions

While using imputation methods of accounting for differences in discontinuation rates, we found onabotulinumtoxinA to have greater clinical utility than topiramate, largely because of tolerability issues associated with the latter and a relatively higher number of onabotulinumtoxinA patients remaining on treatment.
Association of rs2651899 Polymorphism in the Positive Regulatory Domain 16 and Common Migraine Subtypes: A Meta‐Analysis
Authors: Lee Hsun‐Hua , Chen Chih‐Chung , Ong Jiann‐Ruey , Lin Yuan‐Feng , Lee Fei‐Peng , Hu Chaur‐Jong , Wang Yuan‐Hung
Published: September 2019

Background

Migraine is a neurovascular disease with recurrent headache attacks. A polymorphism (rs2651899) of the PRDM16 gene, which is associated with migraine, was identified in recent genome‐wide association studies. The potential role of the PRDM16 rs2651899 polymorphism in migraine is still unknown. Therefore, we conducted this systematic review and meta‐analysis to examine this issue.

Methods

We performed a comprehensive literature search of the PubMed, Embase, and Google Scholar databases to identify eligible studies published before October 2018. Individual odds ratio and 95% confidence interval was used to estimate the pooled strength of the association between the PRDM16 rs2651899 polymorphism and common migraine subtypes, including migraine with aura (MA) and migraine without aura (MO).

Results

Six studies with 2853 cases and 9319 controls that fulfilled the inclusion and exclusion criteria were selected for this meta‐analysis. Of the 6 included studies, 4 studies had available data for MWA and another 4 studies had data for MWoA. Overall, significant migraine risks of 1.257, 1.305, and 1.419 were found under allele model (C vs T), dominant model (C/C+T/C vs T/T), and recessive model (C/C vs T/C+T/T), respectively. In the recessive model, significantly increased risks of 1.454 and 1.546 were found for MA and MO, respectively.

Conclusion

Our major findings suggest that PRDM16 rs2651899 polymorphism is associated with the risk of migraine. Furthermore, we found that PRDM16 rs2651899 polymorphism is significantly related to common migraine subtypes (MA and MO).
‘The Future is Probably Now’: Understanding of illness, uncertainty and end‐of‐life discussions in older adults with heart failure and family caregivers
Authors: Im Jennifer , Mak Susanna , Upshur Ross , Steinberg Leah , Kuluski Kerry
Published: September 2019

Background

Earlier end‐of‐life communication is critical for people with heart failure given the uncertainty and high‐risk of mortality in illness. Despite this, end‐of‐life communication is uncommon in heart failure. Left unaddressed, lack of end‐of‐life discussions can lead to discordant care at the end of life.

Objective

This study explores patients' and caregivers’ understanding of illness, experiences of uncertainty, and perceptions of end‐of‐life discussions in advanced illness.

Design

Interpretive descriptive qualitative study of older adults with heart failure and family caregivers. Fourteen semi‐structured interviews were conducted with 19 participants in Ontario, Canada. Interviews were transcribed verbatim and content analysis was used to analyse the data.

Main results

Understanding of illness was shaped by participants’ illness‐related experiences (e.g. symptoms, hospitalizations and self‐care routines) and the ability to adapt to challenges of illness. Participants were knowledgeable of heart failure management, and yet, were limited in their understanding of the consequences of illness. Participants adapted to the challenges of illness which appeared to influence their perception of overall health. Uncertainty reflected participants’ inability to connect manifestations of heart failure as part of the progression of illness towards the end of life. Most participants had not engaged in prior end‐of‐life discussions.

Conclusion

Detailed knowledge of heart failure management does not necessarily translate to an understanding of the consequences of illness. The ability to adapt to illness‐related challenges may delay older adults and family caregivers from engaging in end‐of‐life discussions. Future research is needed to examine the impact of addressing the consequences of illness in facilitating earlier end‐of‐life communication.
Hemostasis critical values among Iranian clinical laboratories “National Survey of 157 Clinical Laboratories”
Authors: Dorgalaleh Akbar , Shiravand Yavar , Dabbagh Ali , Tabibian Shadi , Hosseini Maryam Sadat , Mansouri Tourghabeh Hassan , Rashidpanah Jamal , Narouei Fateme , Shams Mahmood , Gholami Mohammad Saeed , Saneei Moghaddam Esmaei , Shahreki Hojat
Published: September 2019

Background

Immediate reporting of critical values or test results significantly outside the normal range has a growing role in the management of patients, especially in life‐threatening conditions. Due to the lack of international consensus, diverse approaches are used for determination of thresholds, reporting, documentation, and follow‐up. In this study, we assessed how Iranian laboratories manage critical values for hemostasis.

Methods

We designed a standard questionnaire to assess different aspects of hemostasis critical values, including the number of coagulation tests with a defined critical value, critical values reporting, documentation, and follow‐up policies. All results were self‐reported and correctness of the data was not assessed by the authors.

Results

A total of 166 (66.4%) out of 250 laboratories completed the questionnaire; most (52.4%) were private. About 97% of responding laboratories had a critical values policy. These were defined for 64.3% (n: 27) of all coagulation tests (n: 42) performed in Iranian laboratories. Activated partial thromboplastin time (APTT), prothrombin time/international normalized ratio (PT/INR), platelet count, factor XI, and factor XIII assays had defined critical values among all laboratories performing these tests. Almost all laboratories reported critical values within 1 hour, after confirmation of the result on the same sample (70% of the laboratories) or a new one (13.4% of the laboratories). State and private laboratories had the same critical value reporting policy for in and outpatients, with laboratory technicians reporting critical results to nurses, for the most part.

Conclusion

Although critical value policy is widely used among Iranian laboratories, there is no consensus policy for the reporting of hemostasis critical values, or documentation, threshold determination, and follow‐up processes. It is impossible to determine whether non‐responding laboratories had any critical values reporting policy. Results thus are biased toward laboratories that did.
Sirtuin4 suppresses the anti‐neuroinflammatory activity of infiltrating regulatory T cells in the traumatically injured spinal cord
Authors: Lin Wenping , Chen Wenkai , Liu Weifeng , Xu Zhengquan , Zhang Liqun
Published: September 2019

The neuroinflammation following traumatic spinal cord injury (SCI) is a critical process that impacts both the injury and the recovery of spinal cord parenchyma. Infiltrating regulatory T (Treg) cells are potent anti‐inflammatory cells that restrain post‐SCI neuroinflammation. To understand the molecular mechanisms underlying the activity of infiltrating Treg cells, we used a mouse spinal cord compression injury model to analyze the role of Sirtuins (SIRTs) in the modulation of infiltrating Treg cell functions. We found that the expressions of SIRT4 and SIRT6 were up‐regulated in infiltrating Treg cells. Using lentivirus‐mediated gene expression or RNA interference, we revealed that SIRT4 substantially inhibited the expression of Foxp3, interleukin‐10, and transforming growth factor‐β in Treg cells, whereas SIRT6 had little effect on Treg cells. Consistently, SIRT4 overexpression weakened the suppressive effect of Treg cells on lipopolysaccharide‐stimulated spinal cord CD11b+ myeloid cells. Knock‐down of SIRT4 enhanced the anti‐inflammatory activity of infiltrating Treg cells in the parenchyma of injured spinal cords. Additionally, SIRT4 overexpression blocked in vitro Treg cell generation from conventional T cells. Furthermore, SIRT4 down‐regulated 5′ AMP‐activated protein kinase (AMPK) signaling in Treg cells, whereas the AMPK agonist AICAR restored the expression of Foxp3 and interleukin‐10 in SIRT4‐overexpressing Treg cells. In conclusion, our research unveils a new mechanism by which the post‐SCI neuroinflammation is regulated.
The impact of grape processing and carbonic maceration on the microbiota of early stages of winemaking
Authors: Guzzon R. , Malacarne M. , Larcher R. , Franciosi E. , Toffanin A.
Published: September 2019

Aims

The work investigates the impact of grapes processing at the beginning of winemaking on the composition of microbiota during the oenological fermentations and on the composition of obtained wines.

Methods and Results

The experiments were conducted in a biodynamic winery to exclude interference due to microbial starters. Three winemaking protocols, with different pre-fermentative management of grapes, were followed by plate count and next generation sequencing on 16S for bacteria and internal transcribed spacer sequencing (ITS) for yeast. Chemical and sensory characterization of wine was performed. The grape processing influenced the evolution of microbiota (especially lactic and acetic acid bacteria) and the fermentation rate. The highest biodiversity was observed in the experiment carried out with whole grapes and carbonic maceration, with the presence of bacterial groups not usually found in winemaking (Bacteroidales, Clostridiales, Oscillospira). The different microbiotas influenced the organic acid profile of wines, the content of biogenic ammines and the perception of organoleptic descriptors linked to the vine cultivar (Syrah).

Conclusions

Carbonic maceration impacts on the evolution of the microbiota and the wine features. The absence of addition of starters and sulphur dioxide would seem to be correlated with the high microbial biodiversity.

Significance and Impact of the Study

Carbonic maceration is a traditional winemaking practice, today there are difficulties in its managing because the anaerobiosis stimulates spoilage micro-organisms. The work elucidates the reasons of these difficulties and identified some microbial groups rarely associated with winemaking. The ratio of ethanol accumulation along with physical management of grapes and the supply of oxygen during the early stages of winemaking are powerful instruments of oenological variability, able to offer new possibilities to winemakers in order to defining the quality of red wines.
Exosomes derived from pro‐inflammatory bone marrow‐derived mesenchymal stem cells reduce inflammation and myocardial injury via mediating macrophage polarization
Authors: Xu Ruqin , Zhang Fangcheng , Chai Renjie , Zhou Wenyi , Hu Ming , Liu Bin , Chen Xuke , Liu Mingke , Xu Qiong , Liu Ningning , Liu Shiming
Published: September 2019

Exosomes are served as substitutes for stem cell therapy, playing important roles in mediating heart repair during myocardial infarction injury. Evidence have indicated that lipopolysaccharide (LPS) pre‐conditioning bone marrow‐derived mesenchymal stem cells (BMSCs) and their secreted exosomes promote macrophage polarization and tissue repair in several inflammation diseases; however, it has not been fully elucidated in myocardial infarction (MI). This study aimed to investigate whether LPS‐primed BMSC‐derived exosomes could mediate inflammation and myocardial injury via macrophage polarization after MI. Here, we found that exosomes derived from BMSCs, in both Exo and L‐Exo groups, increased M2 macrophage polarization and decreased M1 macrophage polarization under LPS stimulation, which strongly depressed LPS‐dependent NF‐κB signalling pathway and partly activated the AKT1/AKT2 signalling pathway. Compared with Exo, L‐Exo had superior therapeutic effects on polarizing M2 macrophage in vitro and attenuated the post‐infarction inflammation and cardiomyocyte apoptosis by mediating macrophage polarization in mice MI model. Consequently, we have confidence in the perspective that low concentration of LPS pre‐conditioning BMSC‐derived exosomes may develop into a promising cell‐free treatment strategy for clinical treatment of MI.