Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemotherapy‐related cardiotoxicity: are Australian practitioners missing the point?

It has long been established that cardiotoxicity occurs as a result of exposure to certain chemotherapeutics, particularly anthracyclines. Historically, clinicians equate cardiotoxicity with a poor prognosis, in a small percentage of patients and deem long‐term surveillance as optional. Emerging evidence suggests that anthracycline cardiotoxicity (ACT) is a life‐long risk with an incidence approaching 20%.
Young adults living with inflammatory bowel disease : a phenomenological study

Inflammatory bowel disease (IBD) is a chronic condition affecting the digestive system. It is characterized by periods of exacerbation and remission and often poses many difficulties for those living with the disease. Young adulthood is a period with many life transitions. These transitions coupled with living with inflammatory bowel disease present unique challenges for young adults. The purpose of this study was to explore the experiences of young adults living with inflammatory bowel disease. There was little qualitative research available on the topic of living with inflammatory bowel disease. It was decided that a phenomenological research approach would provide rich, in-depth description, and understanding of the experience. Three young adult women who met specific criteria participated in the research study. Collection of data occurred through un-structured interviews. Colaizzi's (1978) method of data analysis, including bracketing of assumptions, was used to identify seven essential themes, which when combined best describe the women's experience. The seven themes identified were: (1) dealing with symptoms, a constant struggle, (2) embarrassment: trying to hide the condition, (3) uncertainty: it could flare up at anytime, (4) lost time: interfering with normal life, (5) the double edged sword: treatment can be as difficult as the disease, (6) needing to maintain a supportive environment and (7) accepting the challenge of living with IBD. Through phenomenological inquiry into the lived experience of these young adults with inflammatory bowel disease, a greater understanding of their experience was gained. This understanding helps to enhance nursing's knowledge base on the phenomenon.
Receptivity to Volunteering in the Immediate Postretirement Period

Higher rates of volunteering might be expected of elders in the period immediately after retirement because they tend to be in relatively good health and have fewer competing obliga tions. Data from the Commonwealth Productive Aging Survey, a telephone survey of a repre sentative national sample of 2,999 people 55 years of age and older, confirmed findings of previous research that retirement is not associated with higher rates of volunteering. However, in the first and second years following termination of employment, nonvolunteers show a heightened receptivity to volunteering; that is, they indicate more willingness to take on volunteer assignments and an ability to do so than do elders who are employed or who have been out of the workforce for longer periods. The findings suggest that volunteer coordinators should focus volunteer recruiting efforts on elders who are about to leave jobs or who have recently left jobs.
Anti‐tumour strategies aiming to target tumour‐associated macrophages

Tumour‐associated macrophages (TAMs) represent a predominant population of inflammatory cells that present in solid tumours. TAMs are mostly characterized as alternatively activated M2‐like macrophages and are known to orchestrate nearly all stages of tumour progression. Experimental investigations indicate that TAMs contribute to drug‐resistance and radio‐protective effects, and clinical evidence shows that an elevated number of TAMs and their M2 profile are correlated with therapy failure and poor prognosis in cancer patients. Recently, many studies on TAM‐targeted strategies have made significant progress and some pilot works have achieved encouraging results. Among these, connections between some anti‐tumour drugs and their influence on TAMs have been suggested. In this review, we will summarize recent advances in TAM‐targeted strategies for tumour therapy. Based on the proposed mechanisms, those strategies are grouped into four categories: (i) inhibiting macrophage recruitment; (ii) suppressing TAM survival; (iii) enhancing M1‐like tumoricidal activity of TAMs; (iv) blocking M2‐like tumour‐promoting activity of TAMs. It is desired that further attention be drawn to this research field and more effort be made to promote TAM‐targeted tumour therapy.
Interleukin‐17A: a unique pathway in immune‐mediated diseases: psoriasis, psoriatic arthritis and rheumatoid arthritis

Experimental evidence points to the importance of the cytokine interleukin‐17A (IL‐17A) in the pathogenesis of several immunoinflammatory diseases including psoriasis, psoriatic arthritis and rheumatoid arthritis. Although a principal effector of T helper type 17 cells, IL‐17A is produced by many other cell types including CD8+ T cells and γδ T cells, and is found at high levels associated with mast cells and neutrophils at sites of skin and joint disease in humans. IL‐17A up‐regulates expression of numerous inflammation‐related genes in target cells such as keratinocytes and fibroblasts, leading to increased production of chemokines, cytokines, antimicrobial peptides and other mediators that contribute to clinical disease features. Importantly, IL‐17A must be considered within the context of the local microenvironment, because it acts synergistically or additively with other pro‐inflammatory cytokines, including tumour necrosis factor. Several direct IL‐17A inhibitors have shown promising activity in proof of concept and phase 2 clinical studies, thereby providing confirmation of experimental data supporting IL‐17A in disease pathogenesis, although levels of response are not predicted by pre‐clinical findings. IL‐17A inhibitors produced rapid down‐regulation of the psoriasis gene signature and high clinical response rates in patients with moderate‐to‐severe plaque psoriasis, consistent with an important role for IL‐17A in psoriasis pathogenesis. Clinical response rates with IL‐17A inhibitors in psoriatic arthritis and rheumatoid arthritis, however, were improved to a lesser degree compared with placebo, suggesting that IL‐17A is either important in a subset of patients or plays a relatively minor role in inflammatory joint disease. Ongoing phase 3 clinical trials should provide further information on the role of IL‐17A in these diseases.
Hamstring to quadriceps strength ratio and noncontact leg injuries: A prospective study during one season

Previous studies have proposed that thigh muscle imbalance is a critical risk factor for the athletic non-contact knee injuries. However, there is a little consensus among prospective studies with regard to the correlation between isokin etic hamstring to quadriceps strength ratio (HQR) and the non-contact knee injury rates. Most of athletic movements at risk are closed kinetic chain movements, and compensatory effect among ankle, knee, and hip joints during the closed kinetic chain movement was observed in the previous literatures. Therefore, it is a ssumed that hamstrings and quadriceps (H:Q) imbalance can cause non-contact lower extremity injuries without necessarily causing knee injuries. The purpose of this study was to prospectively investigate the relationship between H:Q strength imbalance and overall non-contact lower extremity injuries. A prospective cohort study was conducted on NCAA division III basketball and soccer players during one season. A total of eighty two NCAA Division III athletes (41 female (19.56 ± 1.34 yrs, 68.2 ± 10.84 kg, 166.3 ± 6.78 cm) and 40 male (19.97 ± 1.43 yrs, 75.45 ± 8.23 kg, 173.21 ± 7.65 cm)) volunteered to participate in this study which tested Q and H strength at 60 � /s. A trend (p < 0.05) indicating that lower than 60% of HQR was associated with non-contact leg injuries was apparent. This suggests that the H:Q imbalance may be of significance in athletic non-contact leg injuries.
The Emergence and Development of Physiological Regulatory Systems of Newborn Infants in a Neonatal Intensive Care Unit

In the life of a human being, the early neonatal period is the most prone to life-threatening events. After birth, following the transition from the intrato the extra–uterine environment, babies experience dramatic hemodynamic changes. Once babies begin life in the extrauterine environment, they must regulate their own homeostasis in order to survive. Preterm, low birth weight, newborn are even more vulnerable and require the mechanical support for proper tissue oxygenation and nutrition in order to grow and survive in the extra-uterine environment. The adaptation to extra-uterine life is a slow and difficult process for these babies because of their prematurity. At this critical period, hypothermia, apnoea, respiratory distress, and cardiac instabilities such as bradycardia and hypotension are common features in these newborn babies (Bhatt et al., 2010; Di Fiore et al.,2001; Dransfield et al., 1983; Tirosh et al., 2010; Trevisanuto et al., 2005; Upton, et al., 1992), and the resulting hypoxia may lead to brain damage and cardiac arrest if the medical support of a special incubator equipped with a ventilator and systemic monitoring is not provided a as a “primary life support system”. Therefore, the continuous monitoring of heartbeat, respiration, oxygen saturation, blood pressure and temperature has been integrated into the neonatal intensive care unit (NICU) as a mandatory tool to support the fragile clinical conditions of these infants. Monitoring data collected using non-invasive electrocardiograms have been used to understand the physiological regulatory system of these vulnerable infants. The measurement of heart rate variability has been widely examined using various analytic methods (Ardura et al., 1997; Baldzer et al., 1989; Katona et al.,1980; Patural et al., 2004; Yiallourou et al., 2010). Among them, circadian rhythms have been documented to be a prognostic marker of physiological stability and the maturation of the physiological regulatory system, which can be defined as the long-term regulatory system. The endogenous circadian rhythm is generated by the endogenous biological clock located in the anterior hypothalamic suprachiasmatic nuclei (Panda et al., 2002) and may be modulated by exogenous factors (Reppert & Weaver, 2002). It has been documented in the growing foetus
Impact of 5‐aza‐2′‐deoxycytidine and epigallocatechin‐3‐gallate for induction of human regulatory T cells

The epigenetic regulation of transcription factor genes is critical for T‐cell lineage specification. A specific methylation pattern within a conserved region of the lineage specifying transcription factor gene FOXP3, the Treg‐specific demethylated region (TSDR), is restricted to regulatory T (Treg) cells and is required for stable expression of FOXP3 and suppressive function. We analysed the impact of hypomethylating agents 5‐aza‐2′‐deoxycytidine and epigallocatechin‐3‐gallate on human CD4+ CD25− T cells for generating demethylation within FOXP3‐TSDR and inducing functional Treg cells. Gene expression, including lineage‐specifying transcription factors of the major T‐cell lineages and their leading cytokines, functional properties and global transcriptome changes were analysed. The FOXP3‐TSDR methylation pattern was determined by using deep amplicon bisulphite sequencing. 5‐aza‐2′‐deoxycytidine induced FOXP3‐TSDR hypomethylation and expression of the Treg‐cell‐specific genes FOXP3 and LRRC32. Proliferation of 5‐aza‐2′‐deoxycytidine‐treated cells was reduced, but the cells did not show suppressive function. Hypomethylation was not restricted to FOXP3‐TSDR and expression of master transcription factors and leading cytokines of T helper type 1 and type 17 cells were induced. Epigallocatechin‐3‐gallate induced global DNA hypomethylation to a lesser extent than 5‐aza‐2′‐deoxycitidine, but no relevant hypomethylation within FOXP3‐TSDR or expression of Treg‐cell‐specific genes. Neither of the DNA methyltransferase inhibitors induced fully functional human Treg cells. 5‐aza‐2′‐deoxycitidine‐treated cells resembled Treg cells, but they did not suppress proliferation of responder cells, which is an essential capability to be used for Treg cell transfer therapy. Using a recently developed targeted demethylation technology might be a more promising approach for the generation of functional Treg cells.
Disruption of HLA class II antigen presentation in Burkitt lymphoma: implication of a 47 000 MW acid labile protein in CD4+ T‐cell recognition

While Burkitt lymphoma (BL) has a well‐known defect in HLA class I‐mediated antigen presentation, the exact role of BL‐associated HLA class II in generating a poor CD4+ T‐cell response remains unresolved. Here, we found that BL cells are deficient in their ability to optimally stimulate CD4+ T cells via the HLA class II pathway. This defect in CD4+ T‐cell recognition was not associated with low levels of co‐stimulatory molecules on BL cells, as addition of external co‐stimulation failed to elicit CD4+ T‐cell activation by BL. Further, the defect was not caused by faulty antigen/class II interaction, because antigenic peptides bound with measurable affinity to BL‐associated class II molecules. Interestingly, functional class II–peptide complexes were formed at acidic pH 5·5, which restored immune recognition. Acidic buffer (pH 5·5) eluate from BL cells contained molecules that impaired class II‐mediated antigen presentation and CD4+ T‐cell recognition. Biochemical analysis showed that these molecules were greater than 30 000 molecular weight in size, and proteinaceous in nature. In addition, BL was found to have decreased expression of a 47 000 molecular weight enolase‐like molecule that enhances class II‐mediated antigen presentation in B cells, macrophages and dendritic cells, but not in BL cells. These findings demonstrate that BL likely has multiple defects in HLA class II‐mediated antigen presentation and immune recognition, which may be exploited for future immunotherapies.
Timing and intensity of exposure to interferon‐γ critically determines the function of monocyte‐derived dendritic cells

A growing body of evidence suggests that inflammatory cytokines have a dualistic role in immunity. In this study, we sought to determine the direct effects of interferon‐γ (IFN‐γ) on the differentiation and maturation of human peripheral blood monocyte‐derived dendritic cells (moDC). Here, we report that following differentiation of monocytes into moDC with granulocyte–macrophage colony‐stimulating factor and interleukin‐4, IFN‐γ induces moDC maturation and up‐regulates the co‐stimulatory markers CD80/CD86/CD95 and MHC Class I, enabling moDC to effectively generate antigen‐specific CD4+ and CD8+ T‐cell responses for multiple viral and tumour antigens. Early exposure of monocytes to high concentrations of IFN‐γ during differentiation promotes the formation of macrophages. However, under low concentrations of IFN‐γ, monocytes continue to differentiate into dendritic cells possessing a unique gene‐expression profile, resulting in impairments in subsequent maturation by IFN‐γ or lipopolysaccharide and an inability to generate effective antigen‐specific CD4+ and CD8+ T‐cell responses. These findings demonstrate that IFN‐γ imparts differential programmes on moDC that shape the antigen‐specific T‐cell responses they induce. Timing and intensity of exposure to IFN‐γ can therefore determine the functional capacity of moDC.
Modulational stability of weakly nonlinear wave-trains in media with small- and large-scale dispersions.

In this paper, we revisit the problem of modulation stability of quasi-monochromatic wave-trains propagating in a media with the double dispersion occurring both at small and large wavenumbers. We start with the shallow-water equations derived by Shrira [Izv. , Acad. Sci., USSR, Atmos. Ocean. Phys. (Engl. Transl.) 17, 55-59 (1981)] which describes both surface and internal long waves in a rotating fluid. The small-scale (Boussinesq-type) dispersion is assumed to be weak, whereas the large-scale (Coriolis-type) dispersion is considered as without any restriction. For unidirectional waves propagating in one direction, only the considered set of equations reduces to the Gardner-Ostrovsky equation which is applicable only within a finite range of wavenumbers. We derive the nonlinear Schrödinger equation (NLSE) which describes the evolution of narrow-band wave-trains and show that within a more general bi-directional equation the wave-trains, similar to that derived from the Ostrovsky equation, are also modulationally stable at relatively small wavenumbers k < kc and unstable at k > kc, where kc is some critical wavenumber. The NLSE derived here has a wider range of applicability: it is valid for arbitrarily small wavenumbers. We present the analysis of coefficients of the NLSE for different signs of coefficients of the governing equation and compare them with those derived from the Ostrovsky equation. The analysis shows that for weakly dispersive waves in the range of parameters where the Gardner-Ostrovsky equation is valid, the cubic nonlinearity does not contribute to the nonlinear coefficient of NLSE; therefore, the NLSE can be correctly derived from the Ostrovsky equation.
Evolutionary and molecular facts link the WWC protein family to Hippo signaling.

The scaffolding protein KIBRA (also called WWC1) is involved in the regulation of important intracellular transport processes and the establishment of cell polarity. Furthermore, KIBRA/WWC1 is an upstream regulator of the Hippo signaling pathway that controls cell proliferation and organ size in animals. KIBRA/WWC1 represents only one member of the WWC protein family that also includes the highly similar proteins WWC2 and WWC3. Although the function of KIBRA/WWC1 was studied intensively in cells and animal models, the importance of WWC2 and WWC3 was not yet elucidated. Here, we describe evolutionary, molecular, and functional aspects of the WWC family. We show that the WWC genes arose in the ancestor of bilateral animals (clades such as insects and vertebrates) from a single founder gene most similar to the present KIBRA/WWC1-like sequence of Drosophila. This situation was still maintained until the common ancestor of lancelet and vertebrates. In fish, a progenitor-like sequence of mammalian KIBRA/WWC1 and WWC2 is expressed together with WWC3. Finally, in all tetrapods, the three family members, KIBRA/WWC1, WWC2, and WWC3, are found, except for a large genomic deletion including WWC3 in Mus musculus. At the molecular level, the highly conserved WWC proteins share a similar primary structure, the ability to form homo- and heterodimers and the interaction with a common set of binding proteins. Furthermore, all WWC proteins negatively regulate cell proliferation and organ growth due to a suppression of the transcriptional activity of YAP, the major effector of the Hippo pathway.
Healthcare workers' perceptions and experiences on using mHealth technologies to deliver primary healthcare services: a qualitative evidence synthesis.

This is the protocol for a review and there is no abstract. The objectives are as follows: The review has the following two objectives. To identify, appraise and synthesise qualitative research evidence on healthcare workers’ perceptions and experiences regarding their use of mHealth technologies to provide and support the delivery of primary healthcare services. To identify hypotheses, for subsequent consideration and assessment in effectiveness reviews, about why some technologies are more effective than others.
Animal-Assisted Therapy in Psychiatric Rehabilitation

ABSTRACT Reviews of animal-assisted therapy (AAT) research suggest the need for better controlled and designed research studies to supplement the many case studies and anecdotal reports. This study reports the results of such an investigation where sixty-nine male and female psychiatric inpatients were randomized to either an AAT psychiatric rehabilitation group or a similarly conducted control group without AAT, to test if AAT can improve prosocial behaviors. The Social Behavior Scale was scored daily by an independent rater and patients were monitored for four weeks. A two-group by weeks repeated measure analysis of variance was conducted for each outcome measure. There were no baseline differences between the two groups on demographics or any of the measures, but by week four, patients in the AAT group were significantly more interactive with other patients, scored higher on measures of smiles and pleasure, were more sociable and helpful with others, and were more active and responsive to surroundings. These data suggest that AAT plays an important role in enhancing the benefits of conventional therapy, and demonstrates the benefit of including a non-AAT group for comparison. The study also demonstrates the importance of using longitudinal, repeated measure designs. Previous studies may have failed to find significant effects because they were restricted to shorter intervals for measuring outcomes.
Macrophages play an essential role in antigen‐specific immune suppression mediated by T CD8+ cell‐derived exosomes

Murine contact sensitivity (CS) reaction could be antigen‐specifically regulated by T CD8+ suppressor (Ts) lymphocytes releasing microRNA‐150 in antibody light‐chain‐coated exosomes that were formerly suggested to suppress CS through action on macrophages (Mφ). The present studies investigated the role of Mφ in Ts cell‐exosome‐mediated antigen‐specific suppression as well as modulation of Mφ antigen‐presenting function in humoral and cellular immunity by suppressive exosomes. Mice depleted of Mφ by clodronate liposomes could not be tolerized and did not produce suppressive exosomes. Moreover, isolated T effector lymphocytes transferring CS were suppressed by exosomes only in the presence of Mφ, demonstrating the substantial role of Mφ in the generation and action of Ts cell regulatory exosomes. Further, significant decrease of number of splenic B cells producing trinitrophenyl (TNP) ‐specific antibodies with the alteration of the ratio of serum titres of IgM to IgG was observed in recipients of exosome‐treated, antigen‐pulsed Mφ and the significant suppression of CS was demonstrated in recipients of exosome‐treated, TNP‐conjugated Mφ. Additionally, exosome‐pulsed, TNP‐conjugated Mφ mediated suppression of CS in mice pre‐treated with a low‐dose of cyclophosphamide, suggesting de novo induction of T regulatory (Treg) lymphocytes. Treg cell involvement in the effector phase of the studied suppression mechanism was proved by unsuccessful tolerization of DEREG mice depleted of Treg lymphocytes. Furthermore, the inhibition of proliferation of CS effector cells cultured with exosome‐treated Mφ in a transmembrane manner was observed. Our results demonstrated the essential role of Mφ in antigen‐specific immune suppression mediated by Ts cell‐derived exosomes and realized by induction of Treg lymphocytes and inhibition of T effector cell proliferation.