Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV vaccine research and discovery in the nonhuman primates model: a unified theory in acquisition prevention and control of SIV infection

Purpose of reviewHere we highlight the latest advances in HIV vaccine concepts that will expand our knowledge on how to elicit effective acquisition-prevention and/or control of simian immunodeficiency virus (SIV) replication in the nonhuman primate (NHP) model. Recent findingsIn the context of the promising analyses from the RV144 Thai Trial and the effective control of SIV replication exerted by rhCMV-(SIV) elicited EM CD8 T cells, the HIV field has recently shifted toward vaccine concepts that combine protection from acquisition with effective control of SIV replication. Current studies in the NHP model have demonstrated the efficacy of HIV-neutralizing antibodies via passive transfer, the potential importance of the CD4 Tfh subset, the ability to effectively model the RV144 vaccine trial and the capacity of an Ad26 prime and modified vaccinia Ankara virus boost to elicit Env-specific antibody and cellular responses that both limit acquisition and control heterologous SIVmac251 challenge. SummaryThe latest work in the NHP model suggests that the next generation HIV-1 vaccines should aim to provoke a comprehensive adaptive immune response for both prevention of SIV acquisition as well as control of replication in breakthrough infection.
Launch of the Canadian Neurosurgery Research Collaborative

Evidence-based medicine is at the core of modern clinical decision making. Neurosurgery faces a unique combination of challenges in generating strong clinical evidence, including the rarity and heterogeneity of neurosurgical disease, the complexity of neurosurgical procedures, the high cost involved and difficulty in measuring clinically meaningful outcomes, and the relative lack of long-term outcome assessment. As a result, while Canadian neurosurgical research compares favourably with international efforts, neurosurgery as a field lags behind most other medical specialties in the number of published high-quality randomized controlled trials. Many research networks have been established to facilitate multicentre neurosurgical studies, and they have demonstrated the feasibility and utility of collaboration. These include the International Gamma Knife Research Foundation, the Canadian Spine Outcomes and Research Network, the Spine Oncology Study Group, the Hydrocephalus Clinical Research Network, the Rick Hansen Spinal Cord Injury Registry and the Canadian Critical Care Trials Group. These subspecialty-focused networks provide the infrastructure for a variety of study designs (e.g., retrospective, prospective, observational and interventional), aiming to answer important research questions relevant to their fields. Canadian neurosurgery residents are highly interested in research. A recent survey performed by our group showed that 75% would like to incorporate research as part of their future practice and that 78% would like to work in an academic centre. Moreover, 58% plan on completing an additional research degree (M.Sc. or Ph.D.) during training. Therefore, most Canadian neurosurgery residents retain a significant interest in research and the search for opportunities to build their research portfolio. In the United Kingdom (UK), trainee-led research collaboratives have been established to tackle this problem. The West Midlands Research Collaborative (WMRC) was the first of its kind in the UK to successfully complete and publish a clinical trial of 760 patients recruited from 21 centres looking at the impact of wound edge protection devices on surgical site infection after laparotomy. To date, at least 27 collaboratives have been established in the UK, with the evidence suggesting that these geographically distant groups working in collaboration not only facilitate the completion of large-scale research studies but also enhance the research skills of their participants. Given the evidence favouring the role of trainee-led research collaboratives in facilitating high-quality multicentre studies, we launched the Canadian Neurosurgery Research Collaborative (CNRC) in December of 2015 (www.neuronetwork.ca). The objectives of the CNRC are as follows:
Campylobacter populations in wild and domesticated Mallard ducks (Anas platyrhynchos)

Identifying the Campylobacter genotypes that colonize farmed and wild ducks will help to assess the proportion of human disease that is potentially attributable to the consumption of duck meat and environmental exposure to duck faeces. Comparison of temporally and geographically matched farmed and wild ducks showed that they had different Campylobacter populations in terms of: (i) prevalence, (ii) Campylobacter species and (iii) diversity of genotypes. Furthermore, 92.4% of Campylobacter isolates from farmed ducks were sequence types (STs) commonly associated with human disease, in contrast to just one isolate from the wild ducks. Only one ST, ST-45, was shared between the two sources, accounting for 0.9% of wild duck isolates and 5% of farmed duck isolates. These results indicate that domestic ‘niche’ as well as host type may affect the distribution of Campylobacter, and that husbandry practises associated with intensive agriculture may be involved in generating a reservoir of human disease associated lineages.
EGFR ligands exhibit functional differences in models of paracrine and autocrine signaling

Epidermal growth factor (EGF) family peptides are ligands for the EGF receptor (EGFR). Here, we elucidate functional differences among EGFR ligands and mechanisms underlying these distinctions. In 32D/EGFR myeloid and MCF10A breast cells, soluble amphiregulin (AR), transforming growth factor alpha (TGFα), neuregulin 2 beta, and epigen stimulate greater EGFR coupling to cell proliferation and DNA synthesis than do EGF, betacellulin, heparin-binding EGF-like growth factor, and epiregulin. EGF competitively antagonizes AR, indicating that its functional differences reflect dissimilar intrinsic activity at EGFR. EGF stimulates much greater phosphorylation of EGFR Tyr1045 than does AR. Moreover, the EGFR Y1045F mutation and z-cbl dominant-negative mutant of the c-cbl ubiquitin ligase potentiate the effect of EGF but not of AR. Both EGF and AR stimulate phosphorylation of EGFR Tyr992. However, the EGFR Y992F mutation and phospholipase C gamma inhibitor U73122 reduce the effect of AR much more than that of EGF. Expression of TGFα in 32D/EGFR cells causes greater EGFR coupling to cell proliferation than does expression of EGF. Moreover, expression of EGF in 32D/EGFR cells causes these cells to be largely refractory to stimulation with soluble EGF. Thus, EGFR ligands are functionally distinct in models of paracrine and autocrine signaling and EGFR coupling to biological responses may be specified by competition among functionally distinct EGFR ligands.
Prevalence of behavioral and psychological symptoms of dementia and its association with the degree of cognitive impairment in patients presenting to the National Institute of Mental Health, Sri Lanka

Background Behavioral and psychological symptoms of dementia (BPSD) are a major contributor to high levels of carer burden and poor quality of life in patients with dementia. Optimal management is yet to be determined. It is imperative to understand the occurrence of BPSD with the severity of cognitive impairment, since this would allow caregivers and healthcare workers to predict likely behavioral and psychological issues. Aims To describe the patterns of BPSD among patients admitted to the National Institute of Mental Health (NIMH), Sri Lanka and its association with the degree of cognitive impairment. Methods A cross-sectional descriptive study was carried out among patients diagnosed with dementia admitted to NIMH over a two-year period from 2013. An interviewer administered questionnaire, the mini mental state examination and the Neuropsychiatric Inventory (NPI) were used. Results Of the total 122 patients, 51.6% were females. The mean age was 71.2 years. According to the MMSE scores, the severity of dementia was mild, moderate and severe in 32.8%, 42.6% and 24.6% participants respectively. All were on pharmacological treatment in the form of antipsychotics and/or acetylcholinesterase inhibitors. A majority (96.72%) had BPSD. Frequent symptoms included delusions (42.6%), irritability (41%), appetite changes (34.4%) and depression (32%). Aberrant motor behavior, sleep and night-time behavior disorders were significantly associated with increased severity of dementia, while irritability, disinhibition, agitation, hallucinations and delusions were significantly higher in moderate dementia. Anxiety and depression were mostly seen in mild dementia. Conclusion A majority of participants had BPSD, despite being on pharmacological treatment. There was a statistically significant prevalence in groups of symptoms, according to the degree of cognitive impairment can be seen.
Chronic Diseases and Functional Limitations Among Older Construction Workers in the United States: A 10-Year Follow-up Study

Objectives: To examine the health status of older construction workers in the United States, and how occupation and the aging process affect health in workers' later years. Methods: We analyzed six waves (1998 to 2008) of the Health and Retirement Study, a longitudinal survey of US residents age 50+. The study sample totaled 7200 male workers (510 in construction trades) in the baseline. Multiple logistic regression and paired t tests were conducted to compare health outcomes across occupations and within individuals over time. Results: Compared with white-collar workers, construction workers had increased odds of arthritis, back problems, chronic lung disease, functional limitations, work disability, and work-related injuries after controlling for possible confounders. Conclusions: Safety and health interventions, as well as retirement and pension policy, should meet the needs of older construction workers, who face increasingly chronic health conditions over time.
Age-associated elevation in TLR5 leads to increased inflammatory responses in the elderly

Aging is accompanied by a progressive decline in immune function. Studies have shown age‐related decreases in the expression and signaling efficiency of Toll‐like receptors (TLRs) in monocytes and dendritic cells and dysregulation of macrophage TLR3. Using a multivariable mixed effect model, we report a highly significant increase in TLR5‐induced production of IL‐8 from monocytes of older individuals (P < 0.0001). Elevated IL‐8 is accompanied by increased expression of TLR5, both protein and mRNA, and by increased levels of TLR5‐mediated phosphorylation of MAPK p38 and ERK. We noted incomplete activation of NF‐κB in response to TLR5 signaling in monocytes of elderly donors, as reflected by the absence of an associated increase in the production of TNF‐α. Elevated TLR5 may provide a critical mechanism to enhance immune responsiveness in older individuals.
Examining the Factor Structure of the Self-Compassion Scale in Four Distinct Populations: Is the Use of a Total Scale Score Justified?

ABSTRACT This study examined the factor structure of the Self-Compassion Scale (SCS) using a bifactor model, a higher order model, a 6-factor correlated model, a 2-factor correlated model, and a 1-factor model in 4 distinct populations: college undergraduates (N = 222), community adults (N = 1,394), individuals practicing Buddhist meditation (N = 215), and a clinical sample of individuals with a history of recurrent depression (N = 390). The 6-factor correlated model demonstrated the best fit across samples, whereas the 1- and 2-factor models had poor fit. The higher order model also showed relatively poor fit across samples, suggesting it is not representative of the relationship between subscale factors and a general self-compassion factor. The bifactor model, however, had acceptable fit in the student, community, and meditator samples. Although fit was suboptimal in the clinical sample, results suggested an overall self-compassion factor could still be interpreted with some confidence. Moreover, estimates suggested a general self-compassion factor accounted for at least 90% of the reliable variance in SCS scores across samples, and item factor loadings and intercepts were equivalent across samples. Results suggest that a total SCS score can be used as an overall mesure of self-compassion.
The Nature of the Bias When Studying Only Linkable Person Records: Evidence from the American Community Survey

Record linkage across survey and administrative records sources can greatly enrich data and improve their quality. The linkage can reduce respondent burden and nonresponse follow-up costs. This is particularly important in an era of declining survey response rates and tight budgets. Record linkage also creates statistical bias, however. The U.S. Census Bureau links person records through its Person Identification Validation System (PVS), assigning each record a Protected Identification Key (PIK). It is not possible to reliably assign a PIK to every record, either due to insufficient identifying information or because the information does not uniquely match any of the administrative records used in the person validation process. Non-random ability to assign a PIK can potentially inject bias into statistics using linked data. This paper studies the nature of this bias using the 2009 and 2010 American Community Survey (ACS). The ACS is well-suited for this analysis, as it contains a rich set of person characteristics that can describe the bias. We estimate probit models for whether a record is assigned a PIK. The results suggest that young children, minorities, residents of group quarters, immigrants, recent movers, low-income individuals, and non-employed individuals are less likely to receive a PIK using 2009 ACS. Changes to the PVS process in 2010 significantly addressed the young children deficit, attenuated the other biases, and increased the validated records share from 88.1 to 92.6 percent (person-weighted).
Lessons learned from 15 years of non‐grades‐based selection for medical school

Thirty years ago, it was suggested in the Edinburgh Declaration that medical school applicants should be selected not only on academic, but also on non‐academic, attributes. The main rationale behind extending medical school selection procedures with the evaluation of (non‐academic) personal qualities is that this will lead to the selection of students who will perform better as a doctor than those who are selected on the basis of academic measures only. A second rationale is the expectation that this will lead to a representative health workforce as a result of reduced adverse impact. The aims of this paper are (i) to describe what can be learned about the use of selection criteria other than grades from over 15 years of Dutch experience and (ii) to summarise current knowledge on the issue of adverse impact in relation to non‐grades‐based selection.
Cost‐Effectiveness of Mass Dog Vaccination Campaigns against Rabies in Flores Island, Indonesia

A dynamic deterministic simulation model was developed to determine the cost-effectiveness of different mass dog vaccination strategies against rabies in a dog population representative of a typical village on Flores Island. Cost-effectiveness was measured as public cost per averted dog-rabies case. Simulations started with the introduction of one infectious dog into a susceptible dog population of 399 dogs and subsequently ran for a period of 10 years. The base scenario represented a situation without any control intervention. Evaluated vaccination strategies were as follows: annual vaccination campaigns with short-acting vaccine (immunity duration of 52 weeks) (AV_52), annual campaigns with long-acting vaccine (immunity duration of 156 weeks) (AV_156), biannual campaigns with short-acting vaccine (BV_52) and once-in-2-years campaigns with long-acting vaccine (O2V_156). The effectiveness of the vaccination strategies was simulated for vaccination coverages of 50% and 70%. Cumulative results were reported for the 10-year simulation period. The base scenario resulted in three epidemic waves, with a total of 1274 dog-rabies cases. The public cost of applying AV_52 at a coverage of 50% was US$5342 for a village. This strategy was unfavourable compared to other strategies, as it was costly and ineffective in controlling the epidemic. The costs of AV_52 at a coverage of 70% and AV_156 at a coverage of 70% were, respectively, US$3646 and US$3716, equivalent to US$3.00 and US$3.17 per averted dog-rabies case. Increasing the coverage of AV_156 from 50% to 70% reduced the number of cases by 7% and reduced the cost by US$1452, resulting in a cost-effectiveness ratio of US$1.81 per averted dog-rabies case. This simulation model provides an effective tool to explore the public cost-effectiveness of mass dog vaccination strategies in Flores Island. Insights obtained from the simulation results are useful for animal health authorities to support decision-making in rabies-endemic areas, such as Flores Island.
Conceptualizing the Effect of Community and Neighborhood Factors on Type 2 Diabetes Health Outcomes

The objective of this study was to validate a conceptual framework of the relationship between neighborhood factors and diabetes process and outcomes in type 2 diabetes. Structural equation modeling was used to conduct path analysis to examine relationships between neighborhood characteristics and diabetes self-care and glycemic control based on an adapted conceptual framework. Medication adherence and social cohesion has significant direct effects on glycemic control. There was an indirect effect between social support and glycemic control, where 46% of the effect was mediated by medication adherence. Last, medication adherence, food insecurity, and social cohesion had significant total effects on glycemic control. Furthermore, walking environment, social support, neighborhood safety, and neighborhood problems had significant direct effects on food insecurity. The modified conceptual model was validated using path analysis, and neighborhood characteristics had direct and indirect effects on glycemic control.
Generation of mice with a conditional allele for G6pc

Glucose‐6‐phosphatase‐α (G6Pase‐α or G6PC) catalyzes the hydrolysis of glucose‐6‐phosphate to glucose and is a key enzyme in interprandial glucose homeostasis. Mutations in the human G6PC gene, expressed primarily in the liver, kidney, and intestine, cause glycogen storage disease Type Ia (GSD‐Ia), an autosomal recessive disorder characterized by a disturbed glucose homeostasis. For better understanding of the roles of G6Pase‐α in different tissues and in pathological conditions, we have generated mice harboring a conditional null allele for G6pc by flanking Exon 3 of the G6pc gene with loxP sites. We confirmed the null phenotype by using the EIIa‐Cre transgenic approach to generate mice lacking Exon 3 of the G6pc gene. The resulting homozygous Cre‐recombined null mice manifest a phenotype mimicking G6Pase‐α‐deficient mice and human GSD‐Ia patients. This G6pc conditional null allele will be valuable to examine the consequence of tissue‐specific G6Pase‐α deficiency and the mechanisms of long‐term complications in GSD‐Ia. genesis 47:590–594, 2009. Published 2009 Wiley‐Liss, Inc.
Late Gadolinium-Enhancement Cardiac Magnetic Resonance Identifies Postinfarction Myocardial Fibrosis and the Border Zone at the Near Cellular Level in Ex Vivo Rat Heart

Background—Using a resolution 1000-fold higher than prior studies, we studied (1) the degree to which late gadolinium-enhancement (LGE) cardiac magnetic resonance tracks fibrosis from chronic myocardial infarction and (2) the relationship between intermediate signal intensity and partial volume averaging at distinct “smooth” infarct borders versus disorganized mixtures of fibrosis and viable cardiomyocytes. Methods and Results—Sprague-Dawley rats underwent myocardial infarction by coronary ligation. Two months later, rats were euthanized 10 minutes after administration of 0.3 mmol/kg intravenous gadolinium. LGE images ex vivo at 7 T with a 3D gradient echo sequence with 50×50×50 &mgr;m voxels were compared with histological sections (Masson trichrome). Planimetered histological and LGE regions of fibrosis correlated well (y=1.01x−0.01; R2=0.96; P<0.001). In addition, LGE images routinely detected clefts of viable cardiomyocytes 2 to 4 cells thick that separated bands of fibrous tissue. Although LGE clearly detected disorganized mixtures of fibrosis and viable cardiomyocytes characterized by intermediate signal intensity voxels, the percentage of apparent intermediate signal intensity myocardium increased significantly (P<0.01) when image resolution was degraded to resemble clinical resolution consistent with significant partial volume averaging. Conclusions—These data provide important validation of LGE at nearly the cellular level for detection of fibrosis after myocardial infarction. Although LGE can detect heterogeneous patches of fibrosis and viable cardiomyocytes as patches of intermediate signal intensity, the percentage of intermediate signal intensity voxels is resolution dependent. Thus, at clinical resolutions, distinguishing the peri-infarct border zone from partial volume averaging with LGE is challenging.
The phenotype of loneliness

Goossens' review (2012, this issue) nicely maps the progression of scientific research from its early focus on loneliness as a dysphoric state that results from the discrepancy between a person's ideal and actual social relationships to its current emphasis on the centrality of loneliness to our very nature as a social species, and he argues that developmental science throughout Europe has a great deal to contribute to our understanding of this construct. He concludes that psychologists should care about research on loneliness for five reasons: (i) it is a well-defined phenotype; (ii) it shows both high stability and individual differences in rates of change across years; (iii) it has adaptive value and evolutionary significance; (iv) it has a genetic substrate that is moderated by social environments; and (v) it has self-maintaining features that can lead to adverse mental health outcomes. Goossens' review is rife with information and ideas. We focus here on two additional important reasons and on the phenotype of loneliness.