Miracle-dz/UniFAR-FTUs huggingface dataset:
Body Mass Index and Decline in Cognitive Function in Older Black and White Persons

Background While body mass index (BMI) is higher in black compared to white persons, little is known about BMI and change in cognition in cohorts with a large proportion of blacks. We examine relations of BMI with decline in global cognition and five cognitive domains, in older blacks and whites, and determine whether relations differ by race. Methods Participants were 2,134 persons without baseline dementia (33% black; 75% women; mean age =77.9 [range 53-100] and education = 14.7 years, Mini-Mental State Examination = 28.0), enrolled in one of two longitudinal, community-based cohort studies of aging (Minority Aging Research Study; Rush Memory and Aging Project). Summary scores of global cognition and five domains were based on 19 neuropsychological tests administered annually. Mixed-effects models, controlling for age, sex, education, and race, were used to examine the relation of baseline BMI to change in cognition. Results Baseline BMI = 28.4 units (30.3 in blacks [95% confidence interval (CI): 27.2-27.7]; 27.4 in whites [95% CI: 29.8-30.7]). During a mean annual follow-up of 6 years (SD = 4), lower baseline BMI was related to faster decline in global cognition (p = .002), and semantic memory (p < .001) and episodic memory (p = .004), but not working memory, perceptual speed, or visuospatial ability (all p > .08). The relationship of BMI with change in cognition was not modified by race (all p > .09). Conclusions Late-life lower BMI relates to faster rates of decline in cognition, specifically semantic memory and episodic memory, in both blacks and whites. The effect of BMI on cognition appears to be similar in both racial groups.
Correlates of employment and postsecondary education enrolment in Afghanistan and Iraq veterans with traumatic brain injuries

ABSTRACT Primary Objective: About 20% of Iraq and Afghanistan Veterans have sustained a traumatic brain injury (TBI), which can result in postconcussive symptoms and difficulty transitioning from the military to civilian employment and postsecondary education. To better inform programs help Veterans transition back into civilian life, we evaluated correlates of employment and postsecondary education enrolment among treatment-seeking Veterans with a history of TBI. Research Design: A cross-sectional design, using an archival database of VA medical records, was used to answer these research questions. Methods and Procedures: We examined demographic, TBI-related, postconcussive, psychiatric, and neuropsychological factors in 390 Veterans (86% with mild TBI) to determine what factors were associated with employment or enrolment in postsecondary education. Bivariate correlations and multivariate regression were used. Main Outcomes and Results: age, minority status, and service connected disability ratings were significantly associated with employment and postsecondary education enrolment in a multivariate context, whereas TBI-related factors and neurocognitive, postconcussive, and psychiatric symptom severity were not associated with employment or postsecondary education outcomes. Conclusions: Further research is needed to confirm these findings and to evaluate the contribution of age, minority status, and disability on successful return to work and/or school for Veterans with a history of TBI.
Undifferentiated Pancreatic Carcinomas Display Enrichment for Frequency and Extent of PD-L1 Expression by Tumor Cells

Objectives Programmed death ligand 1 (PD-L1) expression in pancreatic ductal adenocarcinoma (PDA) has been described, but unselected PDAs have shown limited clinical responsiveness to anti-programmed death 1 (PD-1)/PD-L1 therapy. Methods We studied 24 cases of undifferentiated pancreatic carcinoma (UPC) using immunohistochemistry for PD-L1 (E1L3N clone), CD3, CD20, CD68, and DNA mismatch repair proteins in this study. Slides were scored for extent of PD-L1 expression on tumor cells and tumor-infiltrating immune cells. Results PD-L1 expression was more frequent in UPCs than in PDAs (63% vs 15%, P < .01). The extent of PD-L1 expression was greater in UPCs, with 13 (87%) of 15 cases containing 10% or more positive tumor cells compared with three of seven PDAs (P = .05). Both tumor groups showed similar numbers of tumor-infiltrating T cells, B cells, and macrophages. Conclusions UPC is enriched for PD-L1 expression in frequency and extent, relative to conventional PDA. Anti-PD-1/PD-L1 agents may represent a valuable therapeutic approach for this subset of highly aggressive pancreatic carcinoma.
Effectiveness of external cues to facilitate task performance in people with neurological disorders: a systematic review and meta-analysis

Abstract Purpose: To examine in people with neurological disorders, which method/s of providing external cues to improve task performance are most effective. Methods: Medline, EMBASE, and PsycINFO were systematically searched. Two reviewers independently screened, extracted data, and assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: Twenty six studies were included. Studies examined a wide-range of cues including visual, tactile, auditory, verbal, and multi-component cues. Cueing (any type) improved walking speed when comparing cues to no cues (mean difference (95% confidence interval): 0.08 m/s (0.06–0.10), I2 = 68%, low quality of evidence). Remaining evidence was analysed narratively; evidence that cueing improves activity-related outcomes was inconsistent and rated as very low quality. It was not possible to determine which form of cueing may be more effective than others. Conclusion: Providing cues to encourage successful task performance is a core component of rehabilitation, however there is limited evidence on the type of cueing or which tasks benefit most from external cueing. Low-quality evidence suggests there may be a beneficial effect of cueing (any type) on walking speed. Sufficiently powered randomised controlled trials are needed to inform therapists of the most effective cueing strategies to improve activity performance in populations with a neurological disorder. Implications for rehabilitation Providing cues is a core component of rehabilitation and may improve successful task performance and activities in people with neurological conditions including stroke, Parkinson’s disease, Alzheimer’s disease, traumatic brain injury, and multiple sclerosis, but evidence is limited for most neurological conditions with much research focusing on stroke and Parkinson’s disease. Therapists should consider using a range of different types of cues depending on the aims of treatment and the neurological condition. There is currently insufficient evidence to suggest one form of cueing is superior to other forms. Therapists should appreciate that responding optimally to cues may take many sessions to have an effect on activities such as walking. Further studies should be conducted over a longer timeframe to examine the effects of different types of cues towards task performance and activities in people with neurological conditions.
Optimization of liposomal topotecan for use in treating neuroblastoma

The purpose of this work was to develop an optimized liposomal formulation of topotecan for use in the treatment of patients with neuroblastoma. Drug exposure time studies were used to determine that topotecan (Hycamtin) exhibited great cytotoxic activity against SK‐N‐SH, IMR‐32 and LAN‐1 neuroblastoma human cell lines. Sphingomyelin (SM)/cholesterol (Chol) and 1,2‐distearoyl‐sn‐glycero‐3‐phosphocholine (DSPC)/Chol liposomes were prepared using extrusion methods and then loaded with topotecan by pH gradient and copper‐drug complexation. In vitro studies showed that SM/Chol liposomes retained topotecan significantly better than DSPC/Chol liposomes. Decreasing the drug‐to‐lipid ratio engendered significant increases in drug retention. Dose‐range finding studies on NRG mice indicated that an optimized SM/Chol liposomal formulation of topotecan prepared with a final drug‐to‐lipid ratio of 0.025 (mol: mol) was better tolerated than the previously described DSPC/Chol topotecan formulation. Pharmacokinetic studies showed that the optimized SM/Chol liposomal topotecan exhibited a 10‐fold increase in plasma half‐life and a 1000‐fold increase in AUC0–24 h when compared with Hycamtin administered at equivalent doses (5 mg/kg). In contrast to the great extension in exposure time, SM/Chol liposomal topotecan increased the life span of mice with established LAN‐1 neuroblastoma tumors only modestly in a subcutaneous and systemic model. The extension in exposure time may still not be sufficient and the formulation may require further optimization. In the future, liposomal topotecan will be assessed in combination with high‐dose radiotherapy such as 131I‐metaiodobenzylguanidine, and immunotherapy treatment modalities currently used in neuroblastoma therapy.
A Role for Attentional Reorienting During Approximate Multiplication and Division

When asked to estimate the outcome of arithmetic problems, participants overestimate for addition problems and underestimate for subtraction problems, both in symbolic and non-symbolic format. This bias is referred to as operational momentum effect (OM). The attentional shifts account holds that during computation of the outcome participants are propelled too far along a spatial number representation. OM was observed in non-symbolic multiplication and division while being absent in symbolic multiplication and division. Here, we investigate whether (a) the absence of the OM in symbolic multiplication and division was due to the presentation of the correct outcome amongst the response alternatives, putatively triggering verbally mediated fact retrieval, and whether (b) OM is correlated with attentional parameters, as stipulated by the attentional account. Participants were presented with symbolic and non-symbolic multiplication and division problems. Among seven incorrect response alternatives participants selected the most plausible result. Participants were also presented with a Posner task, with valid (70%), invalid (15%) and neutral (15%) cues pointing to the position at which a subsequent target would appear. While no OM was observed in symbolic format, non-symbolic problems were subject to OM. The non-symbolic OM was positively correlated with reorienting after invalid cues. These results provide further evidence for a functional association between spatial attention and approximate arithmetic, as stipulated by the attentional shifts account of OM. They also suggest that the cognitive processes underlying multiplication and division are less prone to spatial biases compared to addition and subtraction, further underlining the involvement of differential cognitive processes.
Hereditary polycystic kidney disease is characterized by lymphopenia across all stages of kidney dysfunction: an observational study

Background Polycystic kidney disease (PKD) is characterized by urinary tract infections and extrarenal abnormalities such as an increased risk of cancer. As mutations in polycystin-1 and -2 are associated with decreased proliferation of immortalized lymphoblastoid cells in PKD, we investigated whether lymphopenia could be an unrecognized trait of PKD. Methods We studied 700 kidney transplant recipients with (n = 126) or without PKD at the time of kidney transplantation between 1 January 2003 and 31 December 2014 at Ghent University Hospital. We also studied 204 patients with chronic kidney disease (CKD) with PKD and 204 matched CKD patients without PKD across comparable CKD strata with assessment between 1 January 1999 and 1 February 2016 at three renal outpatient clinics. We compared lymphocyte counts with multiple linear regression analysis to adjust for potential confounders. We analysed flow cytometric immunophenotyping data and other haematological parameters. Results Lymphocyte counts were 264/µL [95% confidence interval (CI) 144-384] and 345/µL (95% CI 245-445) (both P < 0.001) lower in the end-stage kidney disease (ESKD) and CKD cohort, respectively, after adjustment for age, sex, ln(C-reactive protein) and estimated glomerular filtration rate (in the CKD cohort only). In particular, CD8+ T and B lymphocytes were significantly lower in transplant recipients with versus without PKD (P < 0.001 for both). Thrombocyte and monocyte counts were lower in patients with versus without PKD in both cohorts (P < 0.001 for all analyses except P = 0.01 for monocytes in the ESKD cohort). Conclusion PKD is characterized by distinct cytopenias and especially lymphopenia, independent of kidney function. This finding has the potential to alter our therapeutic approach to patients with PKD.
Very Low Prevalence of Vaccine Human Papillomavirus Types Among 18- to 35-Year Old Australian Women 9 Years Following Implementation of Vaccination

Introduction A quadrivalent human papillomavirus vaccination program targeting females aged 12-13 years commenced in Australia in 2007, with catch-up vaccination of 14-26 year olds through 2009. We evaluated the program's impact on HPV prevalence among women aged 18-35 in 2015. Methods HPV prevalence among women aged 18-24 and 25-35 was compared with prevalence in these age groups in 2005-2007. For women aged 18-24, we also compared prevalence with that in a postvaccine study conducted in 2010-2012. Results For the 2015 sample, Vaccination Register-confirmed 3-dose coverage was 53.3% (65.0% and 40.3% aged 18-24 and 25-35, respectively). Prevalence of vaccine HPV types decreased from 22.7% (2005-2007) and 7.3% (2010-2012), to 1.5% (2015) (P trend < .001) among women aged 18-24, and from 11.8% (2005-2007) to 1.1% (2015) (P = .001) among those aged 25-35. Conclusions This study, reporting the longest surveillance follow-up to date, shows prevalence of vaccine-targeted HPV types has continued to decline among young women. A substantial fall also occurred in women aged 25-35, despite lower coverage. Strong herd protection and effectiveness of less than 3 vaccine doses likely contributed to these reductions.
Vandetanib in pretreated patients with advanced non-small cell lung cancer-harboring RET rearrangement: a phase II clinical trial

Background Chromosomal rearrangements involving RET, which are found in about 1% of non-small cell lung cancer (NSCLC), define a unique molecular subset. We performed this study to examine the efficacy and safety of vandetanib 300 mg daily in this patient population. Patients and methods This study was a multi-center, open-label, phase II clinical trial. Patients were enrolled if they had metastatic or recurrent NSCLC with a RET rearrangement, which was confirmed by fluorescence in situ hybridization, had progressive disease against platinum-based doublet chemotherapy, and had a performance status of 0-2. The primary endpoint was the objective response rate. Results A total of 18 patients were enrolled in this study between July 2013 and October 2015. Patients were aged 35-71 years; three had a performance status of 2, and the majority were a heavily pretreated population (≥ two different previous chemotherapy regimens in 72% of the patients). Among the 17 evaluable patients, three had a partial response (objective response rate = 18%) and eight had a stable disease (disease control rate = 65%). Among these patients, the partial response or disease stabilization was durable for more than 6 months in eight patients. Vandetanib also showed a progression-free survival of 4.5 months, and an overall survival of 11.6 months during a median follow-up duration of 14 months. The safety profile was comparable with previous studies of vandetanib. Most vandetanib-related adverse events were mild with prevalent hypertension and rash (in >70% of patients). Grade 3 toxicity included hypertension (n = 3), QT prolongation (2), and elevation of aminotransferases (1), and as a consequence the dose was reduced in four patients. There were no adverse events associated with grade 4 or 5 toxicity. Conclusion Vandetanib is moderately active in pretreated patients with advanced NSCLC-harboring RET rearrangements.
A Theory of NP-completeness and Ill-conditioning for Approximate Real Computations

We develop a complexity theory for approximate real computations. We first produce a theory for exact computations but with condition numbers. The input size depends on a condition number, which is not assumed known by the machine. The theory admits deterministic and nondeterministic polynomial time recognizable problems. We prove that P is not NP in this theory if and only if P is not NP in the BSS theory over the reals. Then we develop a theory with weak and strong approximate computations. This theory is intended to model actual numerical computations that are usually performed in floating point arithmetic. It admits classes P and NP and also an NP-complete problem. We relate the P vs. NP question in this new theory to the classical P vs. NP problem.
Hysteresis in Mental Workload and Task Performance

Objective: We examine how transitions in task demand are manifested in mental workload and performance in a dual-task setting. Background: Hysteresis has been defined as the ongoing influence of demand levels prior to a demand transition. Authors of previous studies predominantly examined hysteretic effects in terms of performance. However, little is known about the temporal development of hysteresis in mental workload. Method: A simulated driving task was combined with an auditory memory task. Participants were instructed to prioritize driving or to prioritize both tasks equally. Three experimental conditions with low, high, and low task demands were constructed by manipulating the frequency of lane changing. Multiple measures of subjective mental workload were taken during experimental conditions. Results: Contrary to our prediction, no hysteretic effects were found after the high- to low-demand transition. However, a hysteretic effect in mental workload was found within the high-demand condition, which degraded toward the end of the high condition. Priority instructions were not reflected in performance. Conclusion: Online assessment of both performance and mental workload demonstrates the transient nature of hysteretic effects. An explanation for the observed hysteretic effect in mental workload is offered in terms of effort regulation. Application: An informed arrival at the scene is important in safety operations, but peaks in mental workload should be avoided to prevent buildup of fatigue. Therefore, communication technologies should incorporate the historical profile of task demand.
Signals Involved in Regulation of Hepatitis C Virus RNA Genome Translation and Replication

Hepatitis C virus (HCV) preferentially replicates in the human liver and frequently causes chronic infection, often leading to cirrhosis and liver cancer. HCV is an enveloped virus classified in the genus Hepacivirus in the family Flaviviridae and has a single-stranded RNA genome of positive orientation. The HCV RNA genome is translated and replicated in the cytoplasm. Translation is controlled by the Internal Ribosome Entry Site (IRES) in the 5′ untranslated region (5′ UTR), while also downstream elements like the cis-replication element (CRE) in the coding region and the 3′ UTR are involved in translation regulation. The cis-elements controlling replication of the viral RNA genome are located mainly in the 5′- and 3′-UTRs at the genome ends but also in the protein coding region, and in part these signals overlap with the signals controlling RNA translation. Many long-range RNA–RNA interactions (LRIs) are predicted between different regions of the HCV RNA genome, and several such LRIs are actually involved in HCV translation and replication regulation. A number of RNA cis-elements recruit cellular RNA-binding proteins that are involved in the regulation of HCV translation and replication. In addition, the liver-specific microRNA-122 (miR-122) binds to two target sites at the 5′ end of the viral RNA genome as well as to at least three additional target sites in the coding region and the 3′ UTR. It is involved in the regulation of HCV RNA stability, translation and replication, thereby largely contributing to the hepatotropism of HCV. However, we are still far from completely understanding all interactions that regulate HCV RNA genome translation, stability, replication and encapsidation. In particular, many conclusions on the function of cis-elements in HCV replication have been obtained using full-length HCV genomes or near-full-length replicon systems. These include both genome ends, making it difficult to decide if a cis-element in question acts on HCV replication when physically present in the plus strand genome or in the minus strand antigenome. Therefore, it may be required to use reduced systems that selectively focus on the analysis of HCV minus strand initiation and/or plus strand initiation.
Assessment of Convolution Neural Networks for Surficial Geology Mapping in the South Rae Geological Region, Northwest Territories, Canada

Mapping of surficial geology is an important requirement for broadening the geoscience database of northern Canada. Surficial geology maps are an integral data source for mineral and energy exploration. Moreover, they provide information such as the location of gravels and sands, which are important for infrastructure development. Currently, surficial geology maps are produced through expert interpretation of aerial photography and field data. However, interpretation is known to be subjective, labour-intensive and difficult to repeat. The expert knowledge required for interpretation can be challenging to maintain and transfer. In this research, we seek to assess the potential of deep neural networks to aid surficial geology mapping by providing an objective surficial materials initial layer that experts can modify to speed map development and improve consistency between mapped areas. Such an approach may also harness expert knowledge in a way that is transferable to unmapped areas. For this purpose, we assess the ability of convolution neural networks (CNN) to predict surficial geology classes under two sampling scenarios. In the first scenario, a CNN uses samples collected over the area to be mapped. In the second, a CNN trained over one area is then applied to locations where the available samples were not used in training the network. The latter case is important, as a collection of in situ training data can be costly. The evaluation of the CNN was carried out using aerial photos, Landsat reflectance, and high-resolution digital elevation data over five areas within the South Rae geological region of Northwest Territories, Canada. The results are encouraging, with the CNN generating average accuracy of 76% when locally trained. For independent test areas (i.e., trained over one area and applied over other), accuracy dropped to 59–70% depending on the classes selected for mapping. In the South Rae region, significant confusion was found between till veneer and till blanket as well as glaciofluvial subclasses (esker, terraced, and hummocky ice-contact). Merging these classes respectively increased accuracy for independent test area to 68% on average. Relative to the more widely used Random Forest machine learning algorithm, this represents an improvement in accuracy of 4%. Furthermore, the CNN produced better results for less frequent classes with distinct spatial structure.