bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the Quality of Cotranscriptional Folding Simulations
Authors: Kühnl Felix , Stadler Peter F. , Findeiß Sven 
Published: January 2020

AbstractStructural changes in RNAs are an important contributor to controlling gene expression not only at the post-transcriptional stage but also during transcription. A subclass of riboswitches and RNA thermometers located in the 5’ region of the primary transcript regulates the downstream functional unit – usually an ORF – through premature termination of transcription. Such elements not only occur naturally but they are also attractive devices in synthetic biology. The possibility to design such riboswitches or RNA thermometers is thus of considerable practical interest. Since these functional RNA elements act already during transcription, it is important to model and understand the dynamics of folding and, in particular, the formation of intermediate structures concurrently with transcription. Cotranscriptional folding simulations are therefore an important step to verify the functionality of design constructs before conducting expensive and labour-intensive wet lab experiments. For RNAs, full-fledged molecular dynamics simulations are far beyond practical reach both because of the size of the molecules and the time scales of interest. Even at the simplified level of secondary structures further approximations are necessary. The BarMap approach is based on representing the secondary structure landscape for each individual transcription step by a coarse-grained representation that only retains a small set of low-energy local minima and the energy barriers between them. The folding dynamics between two transcriptional elongation steps is modeled as a Markov process on this representation. Maps between pairs of consecutive coarse-grained landscapes make it possible to follow the folding process as it changes in response to transcription elongation.In its original implementation, the BarMap software provides a general framework to investigate RNA folding dynamics on temporally changing landscapes. It is, however, difficult to use in particular for specific scenarios such as cotranscriptional folding. To overcome this limitation, we developed the user-friendly BarMap-QA pipeline described in detail in this contribution. It is illustrated here by an elaborate example that emphasizes the careful monitoring of several quality measures. Using an iterative workflow, a reliable and complete kinetics simulation of a synthetic, transcription regulating riboswitch is obtained using minimal computational resources. All programs and scripts used in this contribution are free software and available for download as a source distribution for Linux®, or as a platform-independent Docker®image including support for Apple macOS®and Microsoft Windows®.
Material-Driven Fibronectin Assembly Rescues Matrix Defects due to Mutations in Collagen IV in Fibroblasts
Authors: Mpoyi Elie Ngandu , Cantini Marco , Sin Yuan Yan , Fleming Lauren , Zhou Dennis W. , Costell Mercedes , Lu Yinhui , Kadler Karl , García Andrés J. , Van Agtmael Tom , Salmeron-Sanchez Manuel 
Published: January 2020

AbstractBasement membranes (BMs) provide structural support to tissues and influence cell signaling. Mutations in COL4A1/COL4A2, a major BM component, cause eye, kidney and cerebrovascular disease, including stroke. Common variants in these genes are risk factors for intracerebral hemorrhage in the general population. However, the contribution of the matrix to the disease mechanism(s) and its effects on the biology of cells harboring a collagen IV mutation remain poorly understood. To shed light on this, we engineered controlled microenvironments using polymer biointerfaces coated with ECM proteins laminin or fibronectin (FN), to investigate the cellular phenotype of primary fibroblasts harboring aCOL4A2+/G702Dmutation. FN nanonetworks assembled on poly(ethyl acrylate) (PEA) induced increased deposition and assembly of collagen IV inCOL4A2+/G702Dcells, which was associated with reduced ER size and enhanced levels of protein chaperones such as BIP, suggesting increased protein folding capacity of cells. FN nanonetworks on PEA also partially rescued the reduced stiffness of the deposited matrix and cells, and enhanced cell adhesion through β1-mediated signaling and actin-myosin contractility, effectively rescuing some of the cellular phenotypes associated withCOL4A1/4A2mutations. Collectively, these results suggest that biomaterials are able to shape the matrix and cellular phenotype of theCOL4A2+/G702Dmutation in patient-derived cells.
The differential association of workplace conflicts on employee well-being
Authors: Kuriakose Vijay , S. Sreejesh , Wilson P.R. , MR Anusree 
Published: January 2020

PurposeThe purpose of this study is to examine the differential association of three different workplace conflicts on employee-related outcomes, such as loneliness and well-being. Further, the study pursues to explore the perceived social support at the workplace as a conditional factor in the relation between different conflict types and employee loneliness.Design/methodology/approachThe data were collected using a self-administered survey from 554 IT employees. Structural equation modelling (SEM) was used to test the study postulations.FindingsThe findings indicated that all three types of conflicts differently associate on both loneliness and well-being. Besides, it found that loneliness works as a mediator between conflict types and employee well-being. Further, perceived social support at the workplace moderates the relationship between different types of conflict, such as relationship, process, task conflicts and employee loneliness at work.Practical implicationsThe study provides helpful directions to HR managers by providing a clear empirical understanding of the types of conflicts and its association on employee-related outcomes. Further, the study highlights the need for developing social support in an organisation during conflict episodes, to manage the adverse association of these conflicts on employee well-being and to restore employee well-being.Originality/valueTo the best of the authors’ knowledge, for the first time, a study has been conducted highlighting the differential association of workplace conflict and employee outcome and indicating its intervening mechanisms and conflict management conditions.
CSR in the Lebanese banking sector: a neo-institutional approach to stakeholders’ legitimacy
Authors: Chedrawi Charbel , Osta Alain , Osta Souheir 
Published: January 2020

PurposeCorporate social responsibility (CSR) has become an issue in the international banking industry, where each bank must assert its stakeholders, the social fabric and the natural environment. In the same time, legitimacy which has become one of the most critical issues for corporations, can be increased in the eyes of other stakeholders or institutions by structurally or procedurally adjusting to institutional influences. By conforming to three external institutional pressures (normative, mimetic and coercive), identified by DiMaggio and Powell (1983), organizations can build, support and gain legitimacy for their activities in specific institutional environments.Design/methodology/approachUsing a qualitative approach, this research highlights the input of neo-institutional theory in the CSR context in top Lebanese banks in Lebanon.FindingsThis paper aims to analyze the impact of neo-institutionalism and the role of stakeholders in legitimizing CSR practices in the Lebanese banking sector.Practical implicationsTop Lebanese banks cannot simply comply with institutional pressures to gain their legitimacy, they need to develop their CSR activities targeted toward legitimacy-building at the local level; as for managers they cannot simply adopt managerial perspectives instrumentally to gain societal support, they need to adapt such perspectives and practices to the local needs as expressed by their internal and external stakeholders.Originality/valueManagers of top Lebanese banks need to proactively engage in managing institutional pressures by adopting and adapting legitimacy-seeking strategies. This study highlights that top Lebanese banks differ in their CSR orientation because of their ownership structure, number of employees and profitability.
Social value analysis: the case of Pompeu Fabra University
Authors: Ayuso Silvia , Sánchez Pablo , Retolaza José Luis , Figueras-Maz Mònica 
Published: January 2020

Purpose
This paper aims to explore how to quantify the social value generated by higher education from a social accounting perspective. The proposed approach is integrated social value (ISV) analysis, a social accounting model that considers both the economic value and the social value created by an organisation for its stakeholders.

Design/methodology/approach
The ISV analysis has been applied to Pompeu Fabra University, following a participatory action research process with representatives of the university and its stakeholders.

Findings
The final ISV includes not only the social value created through the university’s economic activity – captured by economic and financial accounting indicators – but also the specific social value created for the different stakeholders by means of non-market relationships, which were monetised through the use of indicators and financial proxies.

Research limitations/implications
Like other social accounting methodologies, ISV analysis suffers from some limitations regarding data availability and economic pricing, that partly will be resolved with maturation of the methodology and increasing standardisation.

Practical implications
By using appropriate proxies, the non-market value of the university can be monetised and integrated with university’s market value. The social value results become a valuable tool for developing useful indicators for internal management and external communication.

Social implications
The process of measuring the social value created by universities provides a way to meet the rising demands for greater accountability and transparency and facilitates engagement with stakeholders on how these institutions are contributing to a sustainable society.

Originality/value
ISV is a recently proposed social accounting model that combines an organisation’s economic and social results into a single concept of value creation and thus contributes to advance the field of social accounting.
Use of micronutrient supplements in pregnant women of south‐east Queensland
Authors: McAlpine Janelle M. , Vanderlelie Jessica J. , Vincze Lisa J. , Perkins Anthony V. 
Published: January 2020

BackgroundMultiple micronutrient supplement use in the Australian pregnant population is rising, despite little evidence of benefit in low‐risk women. While some supplement recommendations are grounded in high‐quality evidence, others warrant further investigation. This highlights a research gap regarding appropriate use of supplements during pregnancy in the Australian population.AimsTo describe micronutrient supplement use during pregnancy in the context of current evidence and national recommendations in a population of south‐east Queensland women.Material and MethodsA cross‐sectional observational design was used to examine data gathered from pregnant women aged 16–44 years residing in south‐east Queensland, Australia. Women were recruited to the study between 23 May 2016 and 30 September 2017.ResultsPregnancy multivitamin use was declared by 42% of the cohort, with 26.8% declaring multivitamins in combination with individual micronutrients and 9.8% declaring specific micronutrient supplement use. Nulliparous women were more likely to declare use of supplements than their multiparous peers (adjusted odds ratio (aOR) 1.938, 95% CI 1.053–3.571,P = 0.034); smoking (aOR 2.717, 95% CI 1.011–7.302,P = 0.047) and low socio‐economic status were associated with no supplement use (aOR 2.451, 95% CI 1.010–5.949,P = 0.048).ConclusionsCurrent recommendations regarding micronutrient supplements throughout pregnancy are based on varying degrees of evidence, resulting in supplement advice of poor cohesion and consistency. Adherence to micronutrient supplement recommendations in the peri‐conception period in this population was poor; second and third trimester supplement use was high. Contemporary empirical research is required to determine what constitutes appropriate supplementation in high‐income regions and the populations they will benefit most.
Access and outcomes of general practitioner obstetrician (rural generalist)‐supported birthing units in Queensland
Authors: Tennett Debra , Kearney Lauren , Kynn Mary 
Published: January 2020

AbstractObjectiveTo describe characteristics and outcomes of women birthing within GP‐obstetrician (rural generalist) supported rural (level 3) obstetric units in Queensland.DesignRetrospective descriptive study.Setting21 GP‐obstetrician supported birthing units in Queensland.ParticipantsWomen (n = 3111) birthing from January 2017 to December 2017.Main outcome measuresPatient, pregnancy and labour characteristics and key maternal and neonatal outcomes routinely recorded in the Queensland Perinatal Data Collection and Queensland Hospital Admitted Patient Data Collection were compared to Queensland public hospital aggregate data.ResultsWomen birthing in rural maternity units were significantly more likely to be Aboriginal or Torrs Strait Islander (16% v 9%), < 20 years old (7% v 4%), term deliveries (96% v 91%), achieve spontaneous onset of labour (67% v 51%), and birth (71% v 60%) (p<0.001) compared with all Queensland public hospitals. They were significantly less likely to be nulliparous (36% v 40%), use pharmacological analgesia (65% v 69%), or have continuous electronic fetal monitoring in labour (54% v 66%) (p<0.001). Neonatal outcomes were comparable; with no significant difference in stillbirth rate between rural units and all Queensland public hospitals (4.8 v 7.3 per 1000 births). Precipitate delivery was the most common labour complication (36% v 33%) (p<0.001).ConclusionGP‐obstetrician (rural generalist) supported rural birthing units in Queensland provide important access for low and medium risk women to deliver locally, with strong indicators of quality and safety.
Challenges in optimising recovery after emergency laparotomy
Authors: Foss N. B. , Kehlet H. 
Published: January 2020

SummaryStandardised peri‐operative care pathways for patients undergoing emergency laparotomy or laparoscopy for non‐traumatic pathologies have been shown to be inadequate and associated with high morbidity and mortality. Recent research has highlighted this problem and showed that simple pathways with ‘rescue’ interventions have been associated with reduced mortality when implemented successfully. These rescue pathways have focused on early diagnosis and surgery, specialist surgeon and anaesthetist involvement, goal‐directed therapy and intensive or intermediary postoperative care for high‐risk patients. In elective surgery, enhanced recovery has resulted in reduced length of stay and morbidity by the application of procedure‐specific, evidence‐based interventions inside rigorously implemented patient pathways based on multidisciplinary co‐operation. The focus has been on attenuation of peri‐operative stress and pain management to facilitate early recovery. Patients undergoing emergency laparotomy are a heterogeneous group consisting mostly of patients with intestinal perforations and/or obstruction with varying levels of comorbidity and frailty. However, present knowledge of the different pathophysiology and peri‐operative trajectory of complications in these patient groups is limited. In order to move beyond rescue pathways and to establish enhanced recovery for emergency laparotomy, it is essential that research on both the peri‐operative pathophysiology of the different main patient groups – intestinal obstruction and perforation – and the potentially differentiated impact of interventions is carried out. Procedure‐ and pathology‐specific knowledge is lacking on key elements of peri‐operative care, such as: multimodal analgesia; haemodynamic optimisation and fluid management; attenuation of surgical stress; nutritional optimisation; facilitation of mobilisation; and the optimal use and organisation of specialised wards and improved interdisciplinary collaboration. As such, the future challenges in improving peri‐operative patient care in emergency laparotomy are moving from simple rescue pathways to establish research that can form a basis for morbidity‐ and procedure‐specific enhanced recovery protocols as seen in elective surgery.
Towards high‐quality peri‐operative care: a global perspective
Authors: Santhirapala V. , Peden C. J. , Meara J. G. , Biccard B. M. , Gelb A. W. , Johnson W. D. , Lipnick M. S. , Makasa E. M. , Martin J. , Maswime S. , Mellin‐Olsen J. , McClain C. D. 
Published: January 2020

SummaryArticle 25 of the United Nations’ Universal Declaration of Human Rights enshrines the right to health and well‐being for every individual. However, universal access to high‐quality healthcare remains the purview of a handful of wealthy nations. This is no more apparent than in peri‐operative care, where an estimated five billion individuals lack access to safe, affordable and timely surgical care. Delivery of surgery and anaesthesia in low‐resource environments presents unique challenges that, when unaddressed, result in limited access to low‐quality care. Current peri‐operative research and clinical guidance often fail to acknowledge these system‐level deficits and therefore have limited applicability in low‐resource settings. In this manuscript, the authors priority‐set the need for equitable access to high‐quality peri‐operative care and analyse the system‐level contributors to excess peri‐operative mortality rates, a key marker of quality of care. To provide examples of how research and investment may close the equity gap, a modified Delphi method was adopted to curate and appraise interventions which may, with subsequent research and evaluation, begin to address the barriers to high‐quality peri‐operative care in low‐ and middle‐income countries.
Discontinuing amiodarone treatment prior to heart transplantation lowers incidence of severe primary graft dysfunction
Authors: Hoemann Benjamin , Takayama Hiroo , Jennings Douglas L. , Han Jiho , Ando Masahiko , Restaino Susan , Colombo Paolo , Farr Maryjane , Naka Yoshifumi , Takeda Koji 
Published: January 2020

AbstractBackgroundRecent studies have shown an increased incidence of primary graft dysfunction (PGD) in patients treated with amiodarone prior to orthotopic heart transplant (OHT). We hypothesized that discontinuation of amiodarone before OHT may lower the incidence of severe PGD.MethodsThis was a single‐center retrospective study of 381 adult OHT recipients between January 2010 and June 2017. Within 6 months prior to OHT, 197 did not receive amiodarone (Group 1), 142 continued amiodarone to OHT (Group 2), and 42 had amiodarone treatment discontinued before OHT (Group 3).Results53 (13.9%) participants developed severe PGD, 13 (6.6%) of which were in Group 1, 36 (25.4%) were in Group 2, and 4 (9.5%) were in Group 3 (P < .001). Multivariable analysis revealed continued amiodarone treatment to OHT (Group 2; OR, 3.70; 95% CI, 1.26‐10.88; P = .018) to be an independent risk factor for the development of severe PGD when Group 1 served as the reference group. Moreover, patients in Group 3 had no difference in the risk of severe PGD (OR = 0.416, 95% CI = 0.08‐2.15; P = .296).ConclusionWe found that discontinuing amiodarone treatment prior to OHT resulted a lower incidence of severe PGD.
The relationship between HbA1c and hypoglycaemia in patients with diabetes treated with insulin degludec versus insulin glargine 100 units/mL
Authors: Philis‐Tsimikas Athena , Lane Wendy , Pedersen‐Bjergaard Ulrik , Wysham Carol , Bardtrum Lars , Harring Signe , Heller Simon 
Published: January 2020

AbstractAimTreat‐to‐target, randomized controlled trials have confirmed lower rates of hypoglycaemia at equivalent glycaemic control with insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine U100) in patients with type 1 (T1D) or type 2 diabetes (T2D). Treat‐to‐target trials are designed to enable comparisons of safety and tolerability at a similar HbA1c level. In this post hoc analysis of the SWITCH 1 and 2 trials, we utilised a patient‐level modelling approach to compare how glycaemic control might differ between basal insulins at a similar rate of hypoglycaemia.Materials and MethodsData for HbA1c and symptomatic hypoglycaemia from the SWITCH 1 and SWITCH 2 trials were analyzed separately for patients with type 1 diabetes and type 2 diabetes, respectively. The association between the individual patient‐level risk of hypoglycaemia and HbA1c was investigated using a Poisson regression model and used to estimate potential differences in glycaemic control with degludec versus glargine U100, at the same rate of hypoglycaemia.ResultsImprovements in glycaemic control increased the incidence of hypoglycaemia with both basal insulins across diabetes types. Our analysis suggests that patients could achieve a mean HbA1c reduction of 0.70 [0.05; 2.20]95% CI (for type 1 diabetes) or 0.96 [0.39; 1.99]95% CI (for type 2 diabetes) percentage points (8 [1; 24]95% CI or 10 [4; 22]95% CI mmol/mol, respectively) further with degludec than with glargine U100 before incurring an equivalent risk of hypoglycaemia.ConclusionOur findings suggest that patients in clinical practice may be able to achieve lower glycaemia targets with degludec versus glargine U100, before incurring an equivalent risk of hypoglycaemia.
Dravet syndrome as part of the clinical and genetic spectrum of sodium channel epilepsies and encephalopathies
Authors: Mei Davide , Cetica Valentina , Marini Carla , Guerrini Renzo 
Published: January 2020

AbstractDravet syndrome is the most studied form of genetic epilepsy. It has now been clarified that the clinical spectrum of the syndrome does not have firmly established boundaries. The core phenotype is characterized by intractable, mainly clonic, seizures precipitated by increased body temperature with onset in the first year of life and subsequent appearance of multiple seizures types still precipitated by, but not confined to, hyperthermia. Cognitive impairment is invariably present when the full syndrome is manifested. This complex of symptoms is related to mutations in the SCN1A gene, which are often de novo and constitutional but can also be inherited from a parent with less severe clinical manifestations or be present as somatic mosaicism. Inheritance from less severely affected individuals, at times only having experienced a few febrile seizures, and differences in severity, even within the same family, with a subset of patients only showing fragments of the syndrome, testify to a remarkable phenotypic heterogeneity as far as severity, but less so clinical phenomenology, are concerned. This characteristic, together with underascertainment of SCN1A mutations due to human errors or technical limitations in uncovering alternative pathogenic molecular mechanisms, such as genomic rearrangements or poison exons, has contributed to making clinicians and geneticists suspicious that Dravet syndrome may be caused by more than one gene. This opinion has been further amplified by the description of other genetic disorders, such as PCDH19‐ or CHD2‐related epilepsy, whose phenotypes have included fragments of the Dravet phenotypic spectrum, and by the suboptimal characterization of phenotypes associated with mutations in SCN1B, HCN1, KCN2A, GABRA1, GABRG2, and STXBP1. The SCN1A gene–Dravet syndrome association is in our opinion highly specific. However, because the syndrome spectrum is wide, fragments of it can at times also be manifested in other genetic epilepsy syndromes, thereby leading to overdiagnosis of Dravet syndrome beyond SCN1A. Dravet syndrome is in turn a severe SCN1A phenotype within a continuum of SCN1A‐related clinical phenomenology.