Miracle-dz/UniFAR-FTUs huggingface dataset:
Redefining the prognostic likelihood of chronic lymphocytic leukaemia patients with borderline percentage of immunoglobulin variable heavy chain region mutations

In chronic lymphocytic leukaemia (CLL), caution is warranted regarding the clinical implications of immunoglobulin variable heavy chain region (IGHV) rearrangements with a ‘borderline’ (BL) percentage of mutations (i.e. 97–97·9% IGHV identity). We analysed the IGHV mutational status in 759 untreated CLL patients (cohort 1). BL‐CLL (n = 36, 5%) showed a time to first treatment (TFT) similar to that of M‐CLL (n = 338) and significantly longer than that of UM‐CLL (n = 385), despite the enrichment in subset #2 cases. In fact, CLLs belonging to subset #2 (n = 15/759, 2%) were significantly more frequent among BL‐CLLs (n = 5/36, 14%), with a brief TFT. TFT of BL‐CLL remained comparable to that of M‐CLL also considering the 327 CLL patients evaluated at diagnosis. These findings were then validated in an independent cohort 2 of 759 newly diagnosed CLL patients (BL‐CLL: n = 11, 1·4%) and in all newly diagnosed patients from cohorts 1 and 2 (n = 1 086, 84% stage A; BL‐CLL: n = 47, 4·3%). BL‐CLL at diagnosis showed a biological profile comparable to that of M‐CLL with a low frequency of unfavourable prognostic markers, except for a significant enrichment in subset #2. Our data suggest that the prognosis of BL‐CLL is good and similar to that of M‐CLL, with the exception of subset #2 cases.
Making it real: the institutionalization of collaboration through formal structure

ABSTRACT Collaboration has achieved widespread acceptance as an indispensable element of healthcare delivery in recent decades, despite modest evidence for its impact on healthcare outcomes. Attempts to understand this seeming paradox have been based mostly in functionalist or conflict-theoretical approaches. Currently lacking, however, is an articulation of how collaborative ideals are embedded in broadly shared beliefs about what healthcare is and how it operates. In this article, we examine how language used in the CanMEDS competency framework and in two guides for Family Health Teams construct idealized versions of rational, autonomous physicians and primary care organizations, respectively. Informed by phenomenological sociology and neo-institutional theory, we characterize these documents as elements of formal structure, the putative “blueprints” for healthcare planning and activity. Drawing on this analysis, we argue that these documents and “collaborative” formal structures in general, not only function as tools to make healthcare more collaborative, but also create an appearance of “real” collaboration, independently of the realities of practice. We argue that they thus instill confidence that the current healthcare system functions according to deep-seated societal values of justice and progress. We conclude by emphasizing the potentially distorting influence of this on efforts to understand and improve healthcare.
Race, gender, and socioeconomic variations in C-reactive protein using the Health and Retirement Study.

OBJECTIVE Clarify the relationships among race, gender, and socioeconomic status (SES) with C-reactive protein (CRP). METHOD The present study analyzed data from 6,521 Black and White respondents aged 51+ in the Health and Retirement Study, a nationally representative sample of midlife and older adults, to address two aims. We sought to (1) assess the independent associations between race, gender, and SES with CRP concentrations; and (2) test whether race, gender, and SES interacted to produce unequal CRP concentrations cross-sectionally and over a four-year follow-up. RESULTS The results demonstrated that race, gender, and SES were each independently associated with baseline CRP, but only SES was associated with CRP at follow-up. Further, race, gender, and education interacted to produce differential CRP levels at baseline. There were incremental benefits for each additional level of education for White men and women, but the relationship between education and CRP was more complicated for Black men and women. Compared to other race/gender groups with less than high school, Black women had the highest and Black men had the lowest levels of CRP. There were no apparent benefits to CRP for Black women with college compared to Black women with high school, while Black men with less than high school and college had similar concentrations of CRP. DISCUSSION In clarifying the complexity inherent in CRP disparities, this work contributes to a greater understanding of the biological mechanisms underlying racial disparities in leading causes of morbidity and mortality in the United States.
Delivering peritoneal dialysis for the multimorbid, frail and palliative patient

Peritoneal dialysis (PD) is only one component of care for older multimorbid, frail and/or palliative patients. Goals of care should be determined for all patients by shared decision-making at the start of during time on PD. Burden of PD should be minimized by individualizing the prescription by allowing for residual renal function and tailored to what is acceptable to the patient. PD facilities should develop the care pathways needed for this group of patients including integration with local geriatric, palliative care and social services
10th European immunogenicity platform open symposium on immunogenicity of biopharmaceuticals

ABSTRACT Therapeutic proteins and emerging gene and cell-based therapies are attractive therapeutic tools for addressing unmet medical needs or when earlier conventional treatment approaches failed. However, the development of an immune response directed against therapeutic agents is a significant concern as it occurs in a substantial number of cases across products and indications. The specific anti-drug antibodies that develop can lead to safety adverse events as well as inhibition of drug activity or accelerated clearance, both phenomena resulting in loss of treatment efficacy. The European Immunogenicity Platform (EIP) is a meeting place for experts and newcomers to the immunogenicity field, designed to stimulate discussion amongst scientists across industry and academia, encourage interactions with regulatory agencies and share knowledge and the state-of-the-art of immunogenicity sciences with the broader scientific community. Here we report on the main topics covered during the EIP 10th Open Symposium on Immunogenicity of Biopharmaceuticals held in Lisbon, 26–27 February 2019, and the 1-d training course on practical and regulatory aspects of immunogenicity held ahead of the conference. These main topics included immunogenicity testing, clinical relevance of immunogenicity, immunogenicity prediction, regulatory aspects, tolerance induction as a mean to mitigate immunogenicity and immunogenicity in the context of gene therapy.
Prescribing peritoneal dialysis for high-quality care in children

Background: Peritoneal dialysis (PD) remains the most widely used modality for chronic dialysis in children, particularly in younger children and in lower and middle income countries (LMICs). We present guidelines for dialysis initiation, modality selection, small solute clearance, and fluid removal in children on PD. A review of the literature and key studies that support these statements are presented. Methods: An extensive Medline search for all publications on PD in children was performed using predefined search criteria. Results: High-quality randomized trials in children are scarce and current clinical practice largely relies on data extrapolated from adult studies or drawn from observational cohort studies in children. The evidence and strength of the recommendation is GRADE-ed, but in the absence of high-quality evidence, the opinion of the authors is provided and must be carefully considered by the treating physician, and adapted to local expertise and individual patient needs as appropriate. We discuss the timing of dialysis initiation, factors to be considered when selecting a dialysis modality, the assessment and management of volume status on PD, achieving optimal small solute clearance, and the importance of preserving residual kidney function. While optimal dialysis must remain the goal for every patient, a careful discussion with fully informed patients and caregivers is important to understand the patient and family’s expectations of dialysis and reasonable adjustments to the dialysis program may be considered in accordance with a philosophy of shared decision-making. Conclusions: There continues to be very poor evidence in the field of chronic PD in children and these recommendations can at best serve to guide clinical decision-making. In LMICs, every effort should be made to conform to the framework of these statements, taking into account resource limitations.
[Role-playing in the teaching-learning process of the nursing degree. Assessment of graduate (profesionals)].

OBJECTIVES To assess role-playing as a methodology in the teaching-learning process for the Nursing Degree. To identify the attitude of alumni (professionals) towards role-playing after entering the job market. INTRODUCTION One of the worst fears of students is facing real situations that they will have to face soon, when they become professionals. Role-playing is a tool that allows the students act out real situations and reduce their concerns. PARTICIPANTS AND CONTEXT Five alumni (nurses) from the Nursing School of the University of Alicante. Academic years 2006-2007 and 2007-2008. METHODOLOGY The reflexive nature of qualitative research is based on symbolic interactionism. COLLECTION OF DATA-SUMMARIES: The subject category chosen is role-playing and it is sorted into subcategories and codes. CONCLUSIONS Findings from the analysis of the summaries have allowed us to see what actually happens when using role-playing as a teaching-learning tool in nursing, and what the consequences are for professionals, once they finish their studies.
The relationship between interferon-gamma (INF-γ) single nucleotide polymorphism +874(T/A) and occurrence risk of aplastic anemia: a meta-analysis

ABSTRACT Objective: This meta-analysis was designed to investigate the association between interferon-gamma (IFN-γ) polymorphisms and occurrence risk of aplastic anemia. Methods: Literature search was conducted in PubMed, Embase and Cochrane Library up to April 2018. The pooled odds ratios (ORs) and 95% confidence interval (CI) were calculated by R 3.12. Results: Total five studies with 304 aplastic anemia patients and 588 controls were included. The statistically significant results were found in the following models: allele genetic model (T vs A: OR = 2.1749, 95% CI = 1.6825–2.8114, P < 0.01), additive genetic model (TA vs AA: OR = 2.1071, 95% CI = 1.3962–3.1799, P < 0.01; TT vs AA: OR = 4.5788, 95% CI = 2.6606–7.8797, P < 0.01), recessive genetic model (TT vs AA + TA: OR = 2.5579, 95% = 1.6680–3.9226, P < 0.01), dominant genetic model (TT + TA vs AA: OR = 2.5599, 95% = 1.7424–3.7611, P < 0.01), the results suggested that the increased occurrence risk of aplastic anemia is significantly associated with the IFN-γ polymorphism. Conclusions: Patients with IFN-γ genotype carrying allele T have higher occurrence risk of aplastic anemia.
C-reactive protein response to influenza vaccination predicts cardiovascular disease risk in the Philippines

ABSTRACT Inflammation is associated with increased risk for chronic degenerative diseases, as well as age-related functional declines across many systems and tissues. Current understandings of inflammation, aging, and human health are based on studies conducted almost exclusively in high-income nations that rely primarily on baseline measures of chronic inflammation. This analysis investigates the inflammatory response to vaccination as a predictor of cardiovascular disease (CVD) among older women in the Philippines, a lower-middle income nation with rising rates of overweight/obesity and relatively high burdens of infectious disease. Concentrations of C-reactive protein (CRP) were measured at baseline and 72 h following influenza vaccination in 530 women (mean age = 55.2 years). Ankle-brachial index (ABI) – an indicator of peripheral arterial disease and broader CVD risk – was measured approximately three years later. The magnitude of CRP response to vaccination was positively associated with ABI, indicating that a larger inflammatory response predicts lower CVD risk. Baseline CRP was negatively associated with CRP response to vaccination, and was not associated with ABI independently of CRP response. These results suggest that research across ecological settings, and with more dynamic measures of inflammatory response and regulation, may yield important insights into the associations among inflammation, aging, and disease.
Risk factors for loss of residual renal function in children with end-stage renal disease undergoing automatic peritoneal dialysis

Background: This study analysed children with end-stage renal disease treated with automated peritoneal dialysis (APD) in our centre to explore the risk factors associated with residual renal function (RRF) loss. Methods: Children treated with APD as the initial renal replacement therapy regimen from January 2008 to December 2016 were included. All the children had a daily urine volume of ≥100 ml/m2 when APD was initiated and a dialysis follow-up time of ≥12 months. A daily urine volume of <100 ml/m2 after 12 months of APD treatment was defined as loss of RRF. Possible risk factors that may be associated with RRF loss were analysed. Results: A total of 66 children were included in the study. After 12 months of APD treatment, the daily urine volume decreased by 377.45 ± 348.80 ml/m2, the residual glomerular filtration rate decreased by 6.39 ± 3.69 ml/min/1.73 m2 and 29 of the patients (43.9%) developed RRF loss. The higher risk of RRF loss after 1 year of APD treatment was most pronounced in patients with daily urine volume of ≤400 ml/m2 before treatment, higher glucose exposure and higher ultrafiltration volume, while the lower risk of RRF loss was in patients with administration of diuretics. Each increase of 1 g/m2/day glucose exposure was associated with a 5% increase in RRF loss (odds ratio (OR) 1.05, p = 0.023) and each increase of 1 ml/m2/day ultrafiltration volume was associated with a 1% increase in RRF loss (OR 1.01, p = 0.013). Conclusion: In children undergoing APD, the risk for loss of RRF is associated with low urine volume at the start of APD, high glucose loading and high peritoneal ultrafiltration volume, while preservation of RRF is associated with the usage of diuretics.
Non-Fasting Triglyceride Levels as a Superior Predictor of Cardiovascular Disease.

performed in the fasting state, although evidence was lacking that fasting lipid profiles were superior to non-fasting profiles for cardiovascular risk assessment. TG levels are H ypercholesterolemia is a well-known predictor of cardiovascular disease. Recently, triglyceride (TG) levels have emerged as a predictor and therapeutic target for the reduction of cardiovascular diseases.1,2 Because lipid profiles are affected by food consumption, the measurement of lipid profiles has conventionally been Article p ?
Two miRNA prognostic signatures of head and neck squamous cell carcinoma: A bioinformatic analysis based on the TCGA dataset

MicroRNAs(miRNAs) are maladjusted in multifarious malignant tumor and can be considered as both carcinogens and tumor‐inhibiting factor. In the present study, we analyzed the miRNAs expression profiles and clinical information of 481 patients with head and neck squamous cell carcinoma (HNSCC) through the TCGA dataset to identify the prognostic miRNAs signature. A total of 114 significantly differentially expressed miRNAs (SDEMs) were identified, consisting of 60 up‐adjusted and 54 down‐adjusted miRNAs. The Kaplan‐Meier survival method identified the prognostic function of 2 miRNAs (miR‐4652‐5p and miR‐99a‐3P). Univariate and multivariate Cox regression analyses indicated that the 2 miRNAs were significant prognostic elements of HNSCC. Furthermore, bioinformatic analysis was conducted by means of 4 online gene predicted toolkits to recognize the target genes, and enrichment analysis was performed on the target genes by DAVID. The outcomes depicted that target genes were correlated with calcium, as well as cell proliferation, circadian entrainment, EGFR, PI3K‐Akt‐mTOR, and P53 signaling pathways. Finally, the PPI network was conducted in view of STRING database and Cytoscape. Eight hub genes were identified by CytoHubba and MCODE app, respectively, CBL, SKP1, H2AFX, HGF, POLR2F, UBE2I, VAMP2, and GNAI2 genes. As a result, we identified 2 miRNAs signatures, 8 hub genes, and significant signaling pathways for estimating the prognosis of HNSCC. In order to further explore the molecular mechanism of HNSCC occurrence and development, more comprehensive basic and clinical studies are needed.
Synchronous duodenum and descending colon metastasis from primary lung neuroendocrine small-cell carcinoma: A case report and review of the literature

Introduction Metastasis to the gastrointestinal tract from lung cancer is very uncommon and is often asymptomatic. Although small bowel metastasis may commonly occur, metastases to the stomach and colon are uncommon. Case report In this paper, we present a previously healthy 57-year-old male patient, a 60-packet per year smoker, who was taken to the emergency room with complaints of increasing abdominal pain, rectal bleeding, weight loss, and dyspnea for the last three months. Endoscopic examination revealed polypoid lesions in the duodenum and the descending colon. We diagnosed neuroendocrine small-cell lung cancer based on histopathological and immunohistochemical staining. Management and outcome: A cisplatin (d1, 60 mg/m2/day)–etoposide (d1 to d3, 120 mg/m2/day) regimen was given every three weeks as palliative chemotherapy. After the three course of chemotherapy, the lung radiograph showed a decline in hilar expansion and there was no pleural effusion. Then, he died of acute respiratory failure two weeks after radiotherapy of brain. Discussion Gastrointestinal tract metastasis of lung cancer is recognized synchronously with or rarely before diagnosis. It is generally recognized after the diagnosis of lung cancer. These patients often have other concurrent body metastases. Prognosis is poor, and survival expectation is short. The most common metastases to the gastrointestinal tract are squamous and large cell lung cancer metastases. Our aim is to emphasize the importance of immunohistochemical examination for masses in the gastrointestinal tract and to present this rare case of synchronous duodenal and colonic metastases of small-cell lung cancer.
Are People Sensitive to Problems in Communication?

Recent research indicates that interpersonal communication is noisy, and that people exhibit considerable insensitivity to problems in communication. Using a dyadic referential communication task, the goal of which is accurate information transfer, this study examined the extent to which interlocutors are sensitive to problems in communication and use other-initiated repairs (OIRs) to address them. Participants were randomly assigned to dyads (N = 88 participants, or 44 dyads) and tried to communicate a series of recurring abstract geometric shapes to a partner across a text-chat interface. Participants alternated between directing (describing shapes) and matching (interpreting shape descriptions) roles across 72 trials of the task. Replicating prior research, over repeated social interactions communication success improved and the shape descriptions became increasingly efficient. In addition, confidence in having successfully communicated the different shapes increased over trials. Importantly, matchers were less confident on trials in which communication was unsuccessful, communication success was lower on trials that contained an OIR compared to those that did not contain an OIR, and OIR trials were associated with lower Director Confidence. This pattern of results demonstrates that (a) interlocutors exhibit (a degree of) sensitivity to problems in communication, (b) they appropriately use OIRs to address problems in communication, and (c) OIRs signal problems in communication.
Low-cost scalable discretization, prediction, and feature selection for complex systems

The introduced data-driven tool allows simultaneous feature selection, model inference, and marked cost and quality gains. Finding reliable discrete approximations of complex systems is a key prerequisite when applying many of the most popular modeling tools. Common discretization approaches (e.g., the very popular K-means clustering) are crucially limited in terms of quality, parallelizability, and cost. We introduce a low-cost improved quality scalable probabilistic approximation (SPA) algorithm, allowing for simultaneous data-driven optimal discretization, feature selection, and prediction. We prove its optimality, parallel efficiency, and a linear scalability of iteration cost. Cross-validated applications of SPA to a range of large realistic data classification and prediction problems reveal marked cost and performance improvements. For example, SPA allows the data-driven next-day predictions of resimulated surface temperatures for Europe with the mean prediction error of 0.75°C on a common PC (being around 40% better in terms of errors and five to six orders of magnitude cheaper than with common computational instruments used by the weather services).
Insights into the dual role of angiogenesis following stroke

Stroke remains a major cause of serious disability due to the brain’s limited capacity to regenerate. Current treatments focus on acute recanalization of the occluded blood vessels; however, currently there are no approved therapy options to regenerate neural circuits and reduce stroke-related disability. To promote recovery, therapeutic angiogenesis has been proposed as a promising target. Although restoration of blood vessels providing oxygen and nutrients to the peri-infarct regions may be beneficial, newly generated capillaries may also carry pathophysiological risk factors that need to be considered. One major concern are adverse effects including edema formation and haemorrhagic transformation due to the comprised endothelial barrier function during vascular remodelling. This brief opinion article will discuss the challenges and the newest advancements of angiogenesis as a therapeutic strategy for ischemic stroke.
“One stroke, with twenty-two people”: exploring prostate cancer survivors' participation in dragon boating

Abstract Purpose: This study qualitatively explores prostate cancer survivors’ experience in joining a dragon boating team and its possible impact on their wellbeing. Design: Qualitative data analysis. Sample: Eleven prostate cancer survivors from a dragon boat team. Methods: Semi-structured interviews and thematic analysis. Findings: The findings support physical benefits of dragon boating, however, the positive impact on the men’s psychosocial wellbeing was more salient. Participation in dragon boating was important for establishing a social support system and positively reframing their cancer experience. Practice Implications: Dragon boating is a novel health promotion strategy for men with PC. Seeking to replicate the positive characteristics of dragon boating in the design of future physical activity interventions should be explored.