Miracle-dz/UniFAR-FTUs huggingface dataset:
Caregiving Systems at the End of Life: How Informal Caregivers and Formal Providers Collaborate

End-of-life care is moving out of hospitals and families are replacing professionals in the delivery of care as death approaches. Guided by concepts from the social care model (Cantor & Brennan, 2000), this qualitative study aimed to explore and describe the interrelationship between informal and formal care in a terminal illness. In-depth interviews with 64 families were audiotaped, transcribed, and coded. Genograms and ecomaps were created to visually represent caregivers’ sources of support and used to analyze caregiving networks. Results indicate that quasi-formal and informal social support become an important link between informal and formal caregiving. As a relative is dying, families value kindness and compassion, clear and straightforward communication, information, anticipatory guidance, and respect for self-determination from formal caregivers.
Range-Finding Study of Risk Factors for Childhood Asthma Development and National Asthma Prevalence

This review explores the recent epidemiological literature to identify possible risk factors for childhood asthma development, as well as the proportion of cases that might be attributable to each factor. Tobacco smoke and house-dust-mite allergy are the only environmental risk factors with firmly established roles in asthma development. Together with genetics, these risk factors probably account for much of childhood asthma development. Suggestive risk factors include cockroach, pet, and mold allergens; low birth weight; small family size; and viral infection. More theoretical risk factors include insufficient breastfeeding, obesity/inactivity, ambient ozone, and living in non-farm settings. National/international trends suggest several risk factors that could play major roles in the rising prevalence of asthma. The “tighter” building construction of modern housing and the increasing time that children spend indoors has undoubtedly increased indoor allergen exposures. Children also spend more time in sedentary activities, with a concomitant decrease in physical activity and increase in obesity. Modern “hygiene” and the changing nature of childhood infection may have also increased asthma prevalence. Mechanisms have been suggested implicating ambient air pollution in asthma development, and there is limited epidemiological evidence supporting this hypothesis. However, this evidence does not resolve why pollution levels have been decreasing throughout the period that asthma rates have risen
Characterization of Monocyte‐Derived Dendritic Cells from Patients with Active and Treated Paracoccidioidomycosis

Cellular immune responses are a significant defence mechanism in human paracoccidioidomycosis (PCM), an endemic mycosis in Latin America; however, little is known about the role of dendritic cells (DCs) in human PCM. We investigated monocyte‐derived DCs from patients with treated (TP) and active PCM (AP) compared with healthy non‐PCM donors (CO). DCs from the TP group showed higher expression of HLA‐DR, CD86 and DC‐SIGN compared with CO, whereas AP showed similar expression to CO. Production of IL‐10 was downregulated by TNF‐α in all groups and lower levels were observed in untreated DCs from AP compared with CO. Conversely, IL‐12p40 was significantly upregulated in the DCs of the TP group. TNF‐α‐activated DCs from the CO group produced significantly lower levels of IL‐12p40 when differentiated from magnetic‐sorted monocytes (MACS) compared with adhered monocyte‐derived DCs. This comparison in the TP group revealed similar levels of IL‐12p40, suggesting a T cell–independent increase in the production of IL‐12p40. Higher expression of surface molecules with increased IL‐12p40 may indicate a better activation of DCs after the treatment of PCM. Our findings suggest that DCs may be crucial in the protective response to Paracoccidioides brasiliensis and that in vitro‐generated DCs might be useful in enhancing antifungal immunity, especially during active PCM.
CHANGES IN BRAIN VOLUME DURING ANESTHESIA: THE EFFECTS OF ANOXIA AND HYPERCAPNIA

This investigation was instigated by an unfortunate anesthetic complication which occurred in the Neurosurgical Service of the Massachusetts General Hospital in 1938. A young woman who was rapidly losing her vision because of a hypophysial adenoma that compressed the optic chiasm had a complicating severe bronchiectasis. Operation was therefore undertaken with only local infiltration anesthesia. The moment the tumor had been satisfactorily exposed, however, the patient lost her nerve and insisted that she be placed under general anesthesia. In view of the extensive bronchiectasis it was decided that a relatively low concentration of nitrous oxide with oxygen might be given. Since an intratracheal tube had not previously been inserted and it was deemed inadvisable to disturb the patient's position sufficiently to insert one, it appeared wiser not to use ether. With the onset of a minor degree of cyanosis as the gas was administered, the exposed cerebral hemisphere began to
Methods for Peptide and Protein Quantitation by Liquid Chromatography-Multiple Reaction Monitoring Mass Spectrometry*

Liquid chromatography-multiple reaction monitoring mass spectrometry of peptides using stable isotope dilution (SID) provides a powerful tool for targeted protein quantitation. However, the high cost of labeled peptide standards for SID poses an obstacle to multiple reaction monitoring studies. We compared SID to a labeled reference peptide (LRP) method, which uses a single labeled peptide as a reference standard for all measured peptides, and a label-free (LF) approach, in which quantitation is based on analysis of un-normalized peak areas for detected MRM transitions. We analyzed peptides from the Escherichia coli proteins alkaline phosphatase and β-galactosidase spiked into lysates from human colon adenocarcinoma RKO cells. We also analyzed liquid chromatography-multiple reaction monitoring mass spectrometry data from a recently published interlaboratory study by the National Cancer Institute Clinical Proteomic Technology Assessment for Cancer network (Addona et al. (2009) Nat. Biotechnol. 27: 633–641), in which unlabeled and isotopically labeled synthetic peptides or their corresponding proteins were spiked into human plasma. SID displayed the highest correlation coefficients and lowest coefficient of variation in regression analyses of both peptide and protein spike studies. In protein spike experiments, median coefficient of variation values were about 10% for SID and 20–30% for LRP and LF methods. Power calculations indicated that differences in measurement error between the methods have much less impact on measured protein expression differences than biological variation. All three methods detected significant (p < 0.05) differential expression of three endogenous proteins in a test set of 10 pairs of human lung tumor and control tissues. Further, the LRP and LF methods both detected significant differences (p < 0.05) in levels of seven biomarker candidates between tumors and controls in the same set of lung tissue samples. The data indicate that the LRP and LF methods provide cost-effective alternatives to SID for many quantitative liquid chromatography-multiple reaction monitoring mass spectrometry applications.
Tai Chi Philosophy and Nursing Epistemology

This article analyzes the philosophy underpinning Tai Chi practice in light of nursing epistemology. The first half of the article reviews the general characteristics of major Chinese philosophical traditions that have been merged in Tai Chi: Confucianism, Daoism, and Buddhism. In the second half, themes of integration and praxis in Tai Chi are linked with Carper's fundamental patterns of knowing in nursing. Tai Chi is a practical fusion of humanistic philosophy with an experiential dimension of movement in a nondualistic foundation. The author argues that TC philosophy can be applied to integrated knowledge development and nursing praxis.
Histochemical and Immunohistochemical Analysis of the Stomach of Rhinella icterica (Anura, Bufonidae)

The stomach of Rhinella icterica was analyzed at light microscopy, employing histochemical techniques, lectin histochemistry, and immunohistochemistry for identifying enteroendocrine cells (EC). Although the stomach was composed of fundic and pyloric regions, its wall is formed by mucosa, submucosa, muscularis, and serosa. The mucosa was lined by a simple columnar mucous epithelium, supported by loose connective tissue. Several tubular, simple glands were composed of mucous neck cells, containing oxynticopeptic cells and EC cells. The mucous neck cells were rich in neutral glycoconjugates. The oxynticopeptic cells were predominant in fundic glands, exhibiting weaker alcianophilic reaction at their apical cytoplasm. Serotonin (5-HT) immunoreactive (IR) cells occurred throughout the entire stomach, preferentially located among mucous cells at upper part of the fundic glands. The muscularis mucosae, formed of smooth muscle, separated the mucosal layer from the submucosa, both of which were constituted by loose connective tissue, but without glands. Lymphoid modules occurred in the mucosa at the boundary at the stomach and the gut. In addition, the muscularis was constituted by two sublayers, the circular internal and the longitudinal external, being recovered by the connective tissue of the serosa.
The Origin of Proteasome-inhibitor Resistant HLA Class I Peptidomes: a Study With HLA-A*68:01*

Some HLA class I molecules bind a significant fraction of their constitutive peptidomes in the presence of proteasome inhibitors. In this study, A*68:01-bound peptides, and their parental proteins, were characterized through massive mass spectrometry sequencing to refine its binding motif, including the nearly exclusive preference for C-terminal basic residues. Stable isotope tagging was used to distinguish proteasome-inhibitor sensitive and resistant ligands. The latter accounted for less than 20% of the peptidome and, like in HLA-B27, arose predominantly from small and basic proteins. Under the conditions used for proteasome inhibition in vivo, epoxomicin and MG-132 incompletely inhibited the hydrolysis of fluorogenic substrates specific for the tryptic or for both the tryptic and chymotryptic subspecificities, respectively. This incomplete inhibition was also reflected in the cleavage of synthetic peptide precursors of A*68:01 ligands. For these substrates, the inhibition of the proteasome resulted in altered cleavage patterns. However these alterations did not upset the balance between cleavage at peptide bonds resulting in epitope destruction and those leading to their generation. The results indicate that inhibitor-resistant HLA class I ligands are not necessarily produced by non-proteasomal pathways. However, their generation is not simply explained by decreased epitope destruction upon incomplete proteasomal inhibition and may require additional proteolytic steps acting on incompletely processed proteasomal products.
Increasing hybridization rate and sensitivity of bead-based assays using isotachophoresis.

We present an electrokinetic technique to increase the reaction rate and sensitivity of bead-based assays. We use isotachophoresis (ITP) to preconcentrate and co-focus target molecules and beads into a single ITP zone. The process achieves rapid mixing, stirring, and strongly increases the binding reaction rate. We demonstrate our assay with quantitative detection of 24 nt single-stranded DNA over a dynamic range of three orders of magnitude and multiplexed detection of ten target species per sample. We show that ITP can achieve approximately the same sensitivity as a well-stirred standard reaction in 60-fold reduced reaction time (20 min versus 20 h). Alternately, compared to standard reaction times of 30 min, we show that 20 min ITP hybridization can achieve 5.3-fold higher sensitivity.
Pregnancy After Microinsert Sterilization With Tubal Occlusion Confirmed by Hysterosalpingogram

BACKGROUND: Introduced to the U.S. market in late 2002 as a permanent method of contraception, a microinsert device is placed hysteroscopically into the fallopian tubes, not requiring incisions or general anesthesia. This report describes a case of pregnancy more than 6 months after a hysterosalpingogram (HSG) confirming bilateral occlusion after microinsert sterilization. CASE: A 30-year-old gravida 1 para 1 woman desired permanent sterilization. The patient underwent microinsert device placement and 6 months later had an HSG that confirmed bilateral tubal occlusion. More than 6 months after the confirmatory HSG, the patient became pregnant and delivered a term infant by cesarean birth. Cornual perforation was noted at surgery. CONCLUSION: This case illustrates pregnancy after microinsertion sterilization and an HSG confirming bilateral tubal occlusion, despite perforation. A microinsert device continues to be a viable option for sterilization.
The Role of Structural Disorder in the Rewiring of Protein Interactions through Evolution*

Structurally disordered regions play a key role in protein-protein interaction networks and the evolution of highly connected proteins, enabling the molecular mechanisms for multiple binding. However, the role of protein disorder in the evolution of interaction networks has only been investigated through the analysis of individual proteins, making it impossible to distinguish its specific impact in the (re)shaping of their interaction environments. Now, the availability of large interactomes for several model organisms permits exploration of the role of disorder in protein interaction networks not only at the level of the interacting proteins but of the interactions themselves. By comparing the interactomes of human, fly, and yeast, we discovered that, despite being much more abundant, disordered interactions are significantly less conserved than their ordered counterparts. Furthermore, our analyses provide evidence that this happens not only because disordered proteins are less conserved but also because they display a higher capacity to rewire their interaction neighborhood through evolution. Overall, our results support the hypothesis that conservation of disorder gives a clear evolutionary advantage, facilitating the change of interaction partners during evolution. Moreover, this mechanism is not exclusive of a few anecdotal cases but a global feature present in the interactome networks of entire organisms.
“You don't know what you are saying ‘Yes’ and what you are saying ‘No’ to”: hospital experiences of older people from minority ethnic communities

ABSTRACT Improving responsiveness to the needs of older people from minority ethnic communities has been emphasised as a goal in England since the publication of the National Service Framework for Older People in 2001. Despite this, people from minority ethnic groups consistently give poorer ratings of their health services than ‘majority’ populations, both in England and across many other health-care systems. Language barriers have been shown to play a particularly important role, and appear to be a stronger predictor of perceived quality of care than ethnic origin per se. This paper reports findings from a larger study exploring older people's experiences of care transitions, focusing on the findings from one case study area which explored the hospital and discharge experiences of older people from minority ethnic communities. A participatory approach was adopted, with older people from the local area collaborating in the design, delivery and analysis of the research as ‘co-researchers’. Twenty-four in-depth narrative interviews were carried out with people who had experienced a recent hospital stay as a patient or a family member providing care and support. Our findings show that many aspects of the hospital experience, including the desire for personalised and humanistic approaches to care, are important to older people irrespective of ethnic background. However, older people from minority ethnic communities can also face language and cultural barriers which negatively affect the quality and experience of care. People who had limited English proficiency struggled to understand, communicate and participate in their care. Where professional services were not available or requested, interpreting was provided informally by other patients, family members, hospital staff in clinical and domestic roles, or not at all. We conclude that targeted strategies are required to ensure appropriate and effective hospital services for a multicultural population.
Characteristics Associated With Discontinuation of Long-Acting Reversible Contraception Within the First 6 Months of Use

OBJECTIVE: To measure discontinuation within 6 months among users of the levonorgestrel intrauterine system, copper intrauterine device (IUD), and etonogestrel implant and identify baseline characteristics associated with early discontinuation. METHODS: This was an analysis of the Contraceptive CHOICE Project, a cohort study of 9,256 participants provided with no-cost contraception and followed with telephone interviews at 3 and 6 months. We used logistic regression to investigate characteristics associated with early discontinuation of the two IUDs and implant and described reasons for discontinuation. RESULTS: A total of 6,167 participants were eligible for this analysis. Follow-up data were available for 5,928 participants; 5,495 (93%) were using their method at 6 months and 433 (7%) had discontinued. Discontinuation rates were 7.3%, 8.0%, and 6.9% for the levonorgestrel intrauterine system, copper IUD, and implant, respectively. After adjusting for age, race, marital status, low socioeconomic status, and history of sexually transmitted infection, we found that unmarried women were slightly more likely to discontinue compared with married women (adjusted odds ratio [OR] 1.26, 95% confidence interval [CI] 1.01–1.59 and adjusted OR 1.62, 95% CI 1.11–2.37, respectively). No other baseline characteristics, including younger age (14–19 years), were associated with early discontinuation. The most common reason given for discontinuation was cramping among IUD users and irregular or frequent bleeding among implant users. CONCLUSION: Rates of discontinuation of long-acting reversible contraception at 6 months is low and not increased in adolescents and young women. Intrauterine devices and the implant should be considered as first-line contraceptive options among all women to reduce unintended pregnancy. LEVEL OF EVIDENCE: II
Metabolic Flux Increases Glycoprotein Sialylation: Implications for Cell Adhesion and Cancer Metastasis*

This study reports a global glycoproteomic analysis of pancreatic cancer cells that describes how flux through the sialic acid biosynthetic pathway selectively modulates a subset of N-glycosylation sites found within cellular proteins. These results provide evidence that sialoglycoprotein patterns are not determined exclusively by the transcription of biosynthetic enzymes or the availability of N-glycan sequons; instead, bulk metabolic flux through the sialic acid pathway has a remarkable ability to increase the abundance of certain sialoglycoproteins while having a minimal impact on others. Specifically, of 82 glycoproteins identified through a mass spectrometry and bioinformatics approach, ∼31% showed no change in sialylation, ∼29% exhibited a modest increase, whereas ∼40% experienced an increase of greater than twofold. Increased sialylation of specific glycoproteins resulted in changes to the adhesive properties of SW1990 pancreatic cancer cells (e.g. increased CD44-mediated adhesion to selectins under physiological flow and enhanced integrin-mediated cell mobility on collagen and fibronectin). These results indicate that cancer cells can become more aggressively malignant by controlling the sialylation of proteins implicated in metastatic transformation via metabolic flux.
Presentation and Outcome of Diabetic Foot Ulcers in Saudi Arabian Patients

OBJECTIVES: The purpose of this study was to evaluate associated risk factors, clinical presentation, and outcome of diabetic foot ulcers (DFUs) in a Saudi Arabian hospital. RESEARCH DESIGN AND METHODS: This is a prospective study of diabetic patients with foot ulcers at Saudi Aramco Medical Services Organization. The participants were referred to a wound care specialist. The study was conducted from December 2003 to December 2004 and included a total of 62 patients (30 men and 32 women). The mean age (SD) was 64.8 years (+ 12 years), with a range from 39 to 82 years. RESULTS: During the study period, 19% (12 of 62) of patients had amputations represented by 2 above-knee amputations, 3 below-knee amputations, and 7 limb-sparing surgeries. All patients with DFUs who underwent surgical amputation had a Wagner Classification of grade 4 (n = 9; 75%) or grade 5 (n = 3; 25%). Three patients (25%) had prior surgical limb-sparing amputations, and 11 (91%) patients were on insulin therapy. The associated risk factors with amputation were hypertension, peripheral vascular disease, absence of pedal pulses, and ischemic heart disease (P < .05). CONCLUSIONS: DFUs continue to be an important cause of morbidity and resulted in an amputation rate of 19%.
iTRAQ Based Quantitative Proteomics Approach Validated the Role of Calcyclin Binding Protein (CacyBP) in Promoting Colorectal Cancer Metastasis*

Keeping continuity with our previous study that revealed direct correlations between CRC metastasis and enhanced CacyBP protein levels, here we attempt to improve our understanding of the mechanisms involved within this enigmatic process. Overexpression of CacyBP (CacyBP-OE) in primary CRC cell and its knock down (CacyBP-KD) in the metastatic CRC cells revealed (through phenotypic studies) the positive impact of the protein on metastasis. Additionally, two individual 4-plex iTRAQ based comparative proteomics experiments were carried out on the CacyBP-OE and CacyBP-KD cells, each with two biological replicates. Mining of proteomics data identified total 279 (63.80% up-regulated and 36.20% down-regulated) proteins to be significantly altered in expression level for the OE set and in the KD set, this number was 328 (48.78% up-regulated and 51.22% down-regulated). Functional implications of these significantly regulated proteins were related to metastatic phenotypes such as cell migration, invasion, adhesion and proliferation. Gene ontology analysis identified integrin signaling as the topmost network regulated within CacyBP-OE. Further detection of caveolar mediated endocytosis in the top hit list correlated this phenomenon with the dissociation of integrins from the focal adhesion complex which are known to provide the traction force for cell movement when transported back to the leading edge. This finding was further supported by the data obtained from CacyBP-KD data set showing down-regulation of proteins necessary for integrin endocytosis. Furthermore, intracellular calcium levels (known to influence integrin mediated cell migration) were found to be lowered in CacyBP-KD cells indicating decreased cell motility and vice versa for the CacyBP-OE cells. Actin nucleation by ARP-WASP complex, known to promote cell migration, was also identified as one of the top regulated pathways in CacyBP-OE cells. In short, this study presents CacyBP as a promising candidate biomarker for CRC metastasis and also sheds light on the underlying molecular mechanism by which CacyBP promotes CRC metastasis.