Miracle-dz/UniFAR-FTUs huggingface dataset:
Dopaminergic modulation of exercise hyperpnoea via D2 receptors in mice

Dopamine is related to behaviour (including arousal, motivation and motor control of locomotion), and its turnover in the brain is increased during exercise. We examined the hypothesis that dopamine D2 receptors contribute to exercise hyperpnoea via central neural pathways using the D2‐like receptor antagonist, raclopride. We simultaneously measured ventilation and pulmonary gas exchange for the first time in mice. Mice injected with saline and raclopride (2 mg (kg body weight)−1; i.p.) were compared for respiratory responses to constant‐load exercise at 6 m min−1. Each mouse was set in an airtight treadmill chamber. In the resting state, raclopride‐treated mice had reduced respiratory frequency (fR) and minute ventilation ( ) compared with saline‐treated mice, but arterial and pulmonary gas exchange were not affected, showing that alveolar ventilation was maintained. Inhalation of hyperoxic gas maintained in saline‐treated mice, and hypercapnic ventilatory responses between the two groups were similar. Treadmill exercise produced an abrupt increase in to a maximal level within 1 min and declined to a steady‐state level in both groups. Raclopride‐treated mice had reduced fR and compared with saline‐treated mice during steady states, but showed a similar increase in fR and at exercise onset. Minute ventilation in the steady state was controlled, along with the increase in pulmonary O2 uptake in both groups, but was lowered in raclopride‐treated mice. Thus, D2 receptors participate in resting breathing patterns to raise fR and exercise hyperpnoea in the steady state, probably through behavioural control and not central motor command, at exercise onset.
Immunoproteomically identified GBAA_0345, alkyl hydroperoxide reductase subunit C is a potential target for multivalent anthrax vaccine

Anthrax is caused by the spore‐forming bacterium Bacillus anthracis, which has been used as a weapon for bioterrorism. Although current vaccines are effective, they involve prolonged dose regimens and often cause adverse reactions. High rates of mortality associated with anthrax have made the development of an improved vaccine a top priority. To identify novel vaccine candidates, we applied an immunoproteomics approach. Using sera from convalescent guinea pigs or from human patients with anthrax, we identified 34 immunogenic proteins from the virulent B. anthracis H9401. To evaluate vaccine candidates, six were expressed as recombinant proteins and tested in vivo. Two proteins, rGBAA_0345 (alkyl hydroperoxide reductase subunit C) and rGBAA_3990 (malonyl CoA‐acyl carrier protein transacylase), have afforded guinea pigs partial protection from a subsequent virulent‐spore challenge. Moreover, combined vaccination with rGBAA_0345 and rPA (protective antigen) exhibited an enhanced ability to protect against anthrax mortality. Finally, we demonstrated that GBAA_0345 localizes to anthrax spores and bacilli. Our results indicate that rGBAA_0345 may be a potential component of a multivalent anthrax vaccine, as it enhances the efficacy of rPA vaccination. This is the first time that sera from patients with anthrax have been used to interrogate the proteome of virulent B. anthracis vegetative cells.
Does collaborating with academia improve industry science?: Evidence from the UK biotechnology sector, 1988-2001

Purpose – To test the effect of public‐private collaboration on research quality in the UK biotechnology industry.Design/methodology/approach – Development of an economic model suggesting that collaboration results in learning gains that lead to higher quality research and subsequently testing of this model using unique data from the UK biotechnology sector from 1988‐2001.Findings – Collaborative research does indeed improve research quality, although the nature of the biotech firm in question seems to be an important factor in determining how strongly positive an effect public‐private collaboration has on research quality.Originality/value – Shows that there exists a growing body of work that points to the increasing value of public‐private interaction for the performance and growth of high technology science‐based firms and industries. However, research on the effects of this interaction on the resulting quality of scientific output is scarce.
Melanocortin 3/4 receptors in paraventricular nucleus modulate sympathetic outflow and blood pressure

• What is the central question of this study? The paraventricular nucleus (PVN) is important in regulating sympathetic activity and blood pressure. This study addresses whether activation of melanocortin 3/4 receptors in the PVN modulates sympathetic activity and blood pressure, and whether intracellular signalling involves the cAMP–protein kinase A pathway. • What is the main finding and its importance? Activation of melanocortin 3/4 receptors in the PVN increases sympathetic outflow and blood pressure via the cAMP–protein kinase A pathway. Melanocortin 3 receptors in the PVN exert a tonic excitatory effect on sympathetic activity. Melanocortin 3/4 receptors in the PVN are a putative therapeutic target to inhibit sympathetic activity.
The regulation of interleukin‐6 implicates skeletal muscle as an integrative stress sensor and endocrine organ

• What is the topic of this review? This review discusses the regulation of the interleukin‐6 (IL‐6) gene and how it is uniquely set up to respond to stress signals in skeletal muscle. We propose that skeletal muscle is a ‘stress sensor’ that responds by releasing highly active endocrine and paracrine proteins, such as IL‐6. • What advances does this highlight? Recent discoveries on the regulation of the IL‐6 gene in various stress exposures have resulted in the emergence of a new potential role for skeletal muscle in life‐threatening stress conditions. Understanding the relationship between IL‐6 secretion and stress may provide new insights into normal adaptive responses to disease, deconditioning, inflammation and ageing.
Estimation of left ventricular stroke volume by impedance cardiography: its relation to the aortic reservoir

• What is the central question of this study? Thoracic impedance has been used to calculate left ventricular stroke volume for decades, while its theoretical basis remains controversial and the parameters generated have not been related satisfactorily to the haemodynamic events. • What is the main finding and what is its importance? We provide mechanistic explanations for the following: (i) why the upstroke of the change in thoracic impedance (ΔZ) waveform is constantly delayed with respect to that of the central aortic pressure; (ii) why the contour of the ΔZ waveform is ‘blunted’ compared with that of the central aortic pressure; (iii) what mechanism is related to the ‘second bump’ of the ΔZ waveform in early diastole (the ‘O‐wave’); and (iv) the mechanism that is likely to be associated with the decreasing ΔZ waveform in later diastole.
Off-label Use of Memantine as Adjunctive Treatment in Schizophrenia: A Retrospective Case Series Study

Abstract Introduction: Memantine, an uncompetitive N-methyl D-aspartate receptor (NMDAR) open-channel blocker holds great promise for its potential clinical effectiveness as add-on therapy to on-going treatment with antipsychotics. Methods: We report here the results of a chart review-based retrospective case series study that examined the effectiveness of off-label use of memantine in patients with schizophrenia when used as adjunctive therapy to standard neuroleptic therapy. Results: 17 of the 26 patients, whose case files were reviewed using a study-specific proforma showed clinical improvement in positive and/or negative psychopathology as well as in cognitive and/or functional domains. The doses of on-going antipsychotic medications could be reduced in a sizeable number of responders. None of the subjects reported serious adverse events. Discussion: Memantine holds great promise as adjunctive therapy for treatment of schizophrenia. Randomized controlled trials, wherein memantine is administered at adequate doses for an adequate period of time to ongoing antipsychotic treatment are required to confirm its efficacy in alleviating symptoms of schizophrenia.
Immobilization increases interleukin‐6, but not tumour necrosis factor‐α, release from the leg during exercise in humans

• What is the central question of this study? Does physical inactivity influence the exercise‐induced release of tumour necrosis factor‐α and interleukin‐6 in healthy humans? In young, healthy subjects, we immobilized one leg for 2 weeks, followed by 45 min two‐legged exercise where one leg served as the control and the other was the previously inactive leg. • What is the main finding and its importance? We found that prior physical inactivity enhances interleukin‐6 release during exercise, and it is released in the blood from the legs during exercise much faster than previously known. However, tumour necrosis factor‐α is not released in the blood with exercise, even from a previously inactive leg.
Drug Shortages: Process for Evaluating Impact on Patient Safety

Purpose Drug shortages can seriously impact patient safety. The objective of this study was to develop safety assessment checklists for use during a drug shortage, whether the same drug is available or an alternative is required. Methods A failure modes and effects analysis (FMEA) was conducted following the Institute for Healthcare Improvement's FMEA tool. Each step of the medication use process was reviewed for the potential impact of a shortage-related event. The likelihood of occurrence, likelihood of detection, and severity of potential harm were determined and rated by a multidisciplinary team. To supplement the results of the FMEA, a survey focusing on the perception of patient safety during a drug shortage was developed and sent to various e-mail lists. These data were used to develop the safety assessment checklists. Results Common safety concerns associated with drug shortages in multiple areas of the medication use process include possible look-alike sound-alike issues and delays in patient care. The FMEA and survey results noted that unfamiliarity with an alternative agent was a high vulnerability during a shortage where an alternative is required. The potential for incorrect doses was the greatest concern during a shortage where the same drug is available, but in a different concentration or presentation. Conclusion Drug shortages create patient safety risks. Safety assessment checklists for use when the same drug is available and when an alternative is required during a drug shortage were developed to aid institutions in preventing patient safety impacts.
The new Australian Health and Physical Education Curriculum: a case of/for gradualism in curriculum reform?

In March 2012, the Australian Curriculum, Assessment and Reporting Authority (ACARA) released for public consultation the Shape Paper for the Australian Curriculum: Health and Physical Education (HPE) that was finalized for publication in August 2012. This paper set out the key propositions for a ‘futures-oriented’ curriculum suggesting that HPE should: take a strengths-based approach; focus on educative outcomes; develop health literacy skills; value learning in, about and through movement; and include an inquiry-based approach. As the Lead Writer of the Shape Paper, I believed my task was to consider both what is and what could be. This Fritz Duras Lecture introduces the research and thinking behind the HPE Shape Paper, helping to illuminate this case of curriculum-making. It also reflexively asks if this case is notable for its gradualism, interrogating the strengths and weaknesses of gradualism as applied in curriculum reform.
Phenotypic clustering of lamin A/C mutations in neuromuscular patients

Background: Mutations in the LMNA gene, encoding human lamin A/C, have been associated with an increasing number of disorders often involving skeletal and cardiac muscle, but no clear genotype/phenotype correlation could be established to date. Methods: We analyzed the LMNA gene in a large cohort of patients mainly affected by neuromuscular or cardiac disease and clustered mutated patients in two groups to unravel possible correlations. Results: We identified 28 variants, 9 of which reported for the first time. The two groups of patients were characterized by clinical and genetic differences: 1) patients with childhood onset displayed skeletal muscle involvement with predominant scapuloperoneal and facial weakness associated with missense mutations; 2) patients with adult onset mainly showed cardiac disorders or myopathy with limb girdle distribution, often associated with frameshift mutations presumably leading to a truncated protein. Conclusions: Our findings, supported by meta-analysis of previous literature, suggest the presence of two different pathogenetic mechanisms: late onset phenotypes may arise through loss of function secondary to haploinsufficiency, while dominant negative or toxic gain of function mechanisms may explain the severity of early phenotypes. This model of patient stratification may help patient management and facilitate future studies aimed at deciphering lamin A/C pathogenesis.
Reinnervation following catheter‐based radio‐frequency renal denervation

What is the topic of this review? Does catheter‐based renal denervation effectively denervate the afferent and efferent renal nerves and does reinnervation occur? What advances does it highlight? Following catheter‐based renal denervation, the afferent and efferent responses to electrical stimulation were abolished, renal sympathetic nerve activity was absent, and levels of renal noradrenaline and immunohistochemistry for tyrosine hydroxylase and calcitonin gene‐related peptide were significantly reduced. By 11 months after renal denervation, both the functional responses and anatomical markers of afferent and efferent renal nerves had returned to normal, indicating reinnervation.
Purls of wisdom: A collectivist study of human information behaviour in a public library knitting group

Purpose – The authors aim to apply a collectivist theoretical framework to the study of human information behaviour and the construction of meaning in a knitting group held in a branch of a large Canadian (Ontario) public library.Design/methodology/approach – The research design was naturalistic and consisted of active participant observation of five knitting group sessions and semi‐structured interviews with 12 group members. Field notes were taken, and both observations and interviews were audio taped and transcribed. Field notes and transcripts were coded qualitatively.Findings – Information practices and contextual factors are mutually constitutive. The location of the circle in a public library, the physical characteristics of the act of knitting, and the social meanings of the activities taking place within the group, including the significance of gender and caring, are integrally linked to HIB in this setting. Findings are described verbally and illustrated through a model.Research limitations/impl.
Does Tourniquet Time in Primary Total Knee Arthroplasty Influence Clinical Recovery?

Abstract There are limited data on the influence of a reduced tourniquet time strategy on the clinical outcome of primary total knee arthroplasty (TKA). The aim of our study was to prospectively compare clinical recovery in two groups of patients undergoing TKA based on differences in tourniquet strategy at the same institution. Group A (40 patients) consisted of TKAs performed by a surgeon using tourniquet from incision to arthrotomy closure, and group B (40 patients) consisted of TKAs performed by another surgeon using tourniquet only during cementation. The surgical technique, implants, perioperative management, and patient demographics were similar between groups. Average tourniquet time was significantly higher in group A (71.7 minutes) as compared with group B (36.8 minutes). The maximum hemoglobin (Hb)/hematocrit (Hct) drop was statistically higher in group B (Hb drop = 3.5 ± 0.9 g/dL; Hct drop = 11 ± 3) as compared with group A (Hb drop = 2.9 ± 0.9 g/dL; Hct drop = 9 ± 2; Hb drop p = 0.01; Hct drop p = 0.002). There were no significant differences in visual analogue scale pain scores, narcotic consumption, ability to straight leg raise during hospital stay, range of motion (ROM) at discharge, as well as isometric quadriceps strength, ROM, Short Form 36 scores, Knee Society scores at 6 weeks, 3 months, and 1 year follow-up with a similar multimodal pain management protocol. Radiographic analysis revealed no differences in cement penetration around the tibial component in any zone. Four patients developed pulmonary embolism (three in group A, one in group B) and five patients underwent manipulation under anesthesia for stiffness (four in group A, one in group B). Thus, the use of a tourniquet only during cementing in TKA increases the hemoglobin drop and does not significantly influence pain or clinical recovery with available numbers, but was associated with a lower incidence of early complications. It is a learned surgical skill which significantly reduces tourniquet time and achieves a similar quality of cementing.
Work and work roles: a context of tasks

– Both task‐based and work‐oriented research approaches have proved their value in information science research. A task is a workable analytical unit of human activity, which brings the level of explication close enough to cater for individual actions and their consequences. Similarly, work and work roles have been effective concepts at explicating the broad patterns of professional information activity. Major issues of the existing approaches are the difficulty of conceptualising the contexts of tasks and the relatively high level of abstraction of a work level scrutiny. The purpose of this paper is to discuss how the concepts of “work”, “work role” and “task” might be integrated into a common research agenda. It is suggested that the explication of work and work roles might serve in providing additional understanding on the formation of the purposes, meanings and values, which guide the shaping of the activities conceptualised as tasks. , – The issue is discussed in general with a reference to an empirical study of information work of archaeology professionals informed by the notion of work role. , – It is suggested that the broader notions of work and work roles are useful concepts for explicating the context of more specific tasks. , – The suggested approach brings together task and work–work role‐based research and provides a basis for exploring human information activity from a broader perspective than before and thus improving the general understanding of why and how information is used as it is used. , – The study provides an approach to conceptualise the ways how people work with information and lays the ground for improving information management and organisation practices. , – There has been little prior discussion about integrating the task and work‐based approaches. The paper suggests that the explication of work and work roles might serve in providing additional understanding on the formation of the purposes, meanings and values, which guide the shaping of the activities conceptualised as tasks.
Facilitation of breathing by leptin effects in the central nervous system

With the global epidemic of obesity, breathing disorders associated with excess body weight have markedly increased. Respiratory dysfunctions caused by obesity were originally attributed to mechanical factors; however, recent studies have suggested a pathophysiological component that involves the central nervous system (CNS) and hormones such as leptin produced by adipocytes as well as other cells. Leptin is suggested to stimulate breathing and leptin deficiency causes an impairment of the chemoreflex, which can be reverted by leptin therapy. This facilitation of the chemoreflex may depend on the action of leptin in the hindbrain areas involved in the respiratory control such as the nucleus of the solitary tract (NTS), a site that receives chemosensory afferents, and the ventral surface of the medulla that includes the retrotrapezoid nucleus (RTN), a central chemosensitive area, and the rostral ventrolateral medulla (RVLM). Although the mechanisms and pathways activated by leptin to facilitate breathing are still not completely clear, evidence suggests that the facilitatory effects of leptin on breathing require the brain melanocortin system, including the POMC–MC4R pathway, a mechanism also activated by leptin to modulate blood pressure. The results of all the studies that have investigated the effect of leptin on breathing suggest that disruption of leptin signalling as caused by obesity‐induced reduction of central leptin function (leptin resistance) is a relevant mechanism that may contribute to respiratory dysfunctions associated with obesity.
Vascular and circulating microRNAs in renal ischaemia–reperfusion injury

Ischaemia–reperfusion (I/R) injury of the kidney is a major cause of acute kidney injury. It may result in worsening or even loss of organ function. Transient occlusion of the renal vessel is followed by a reperfusion period, which induces further tissue damage by release of reactive oxygen and nitrogen species. Ischaemia–reperfusion injury of the kidney may be associated with surgical interventions in native kidneys and is also a common and unavoidable phenomenon in kidney transplantation. MicroRNAs are fascinating modulators of gene expression. They are capable of post‐transcriptional silencing of genetic information by targeting the 3′‐untranslated region of mRNAs, culminating in a suppression of protein synthesis or an increase in mRNA degradation. They might therefore be useful diagnostic and therapeutic entities during renal I/R injury; for instance, miR‐21 has been shown to be enriched in kidney tissue in mice and humans with acute kidney injury. Interestingly, most recent literature suggests that modulation of vascular microRNAs might result in the amelioration of kidney function during renal I/R injury. To that end, miR‐126 and miR‐24, which have been demonstrated to be highly enriched in endothelial cells, were therapeutically modulated and shown to ameliorate renal I/R injury in mice. MicroRNAs in plasma, urine or enriched in microvesicles have been shown to serve as non‐invasive tools for disease monitoring and to have potential impact on downstream mechanisms in recipient cells. This review highlights the latest developments regarding the role of microRNAs in renal I/R injury.
Reductive and generative approaches to management of morphological variation of keywords in monolingual information retrieval: An overview

Purpose – The purpose of this article is to discuss advantages and disadvantages of various means to manage morphological variation of keywords in monolingual information retrieval.Design/methodology/approach – The authors present a compilation of query results from 11 mostly European languages and a new general classification of the language dependent techniques for management of morphological variation. Variants of the different techniques are compared in some detail in terms of retrieval effectiveness and other criteria. The paper consists mainly of an overview of different management methods for keyword variation in information retrieval. Typical IR retrieval results of 11 languages and a new classification for keyword management methods are also presented.Findings – The main results of the paper are an overall comparison of reductive and generative keyword management methods in terms of retrieval effectiveness and other broader criteria.Originality/value – The paper is of value to anyone who wants to.