Miracle-dz/UniFAR-FTUs huggingface dataset:
Beyond Dopamine: GABA, Glutamate, and the Axial Symptoms of Parkinson Disease

Introduction: The axial symptoms of Parkinson disease (PD) include difficulties with balance, posture, speech, swallowing, and locomotion with freezing of gait, as well as axial rigidity. These axial symptoms impact negatively on quality of life for many patients, yet remain poorly understood. Dopaminergic treatments typically have little effect on the axial symptoms of PD, suggesting that disruptions in other neurotransmitter systems beyond the dopamine system may underlie these symptoms. The purpose of the present study was to examine the relationship between the axial symptoms of PD and GABA and glutamate levels quantified with magnetic resonance spectroscopy. Methods: The participant group included 20 patients with PD and 17 healthy control participants. Water-scaled GABA and Glx (glutamate + glutamine) concentrations were derived from GABA-edited MEGA-PRESS spectra acquired from the left basal ganglia and prefrontal cortex, and additional water-scaled Glx concentrations were acquired from standard PRESS spectra acquired from the pons. Spectra were analyzed with LCModel. The axial symptoms of PD were evaluated from subscales of the Unified Parkinson's Disease rating scale (MDS-UPDRS). Results: PD patients demonstrated significantly higher GABA levels in the basal ganglia, which correlated with the degree of gait disturbance. Basal ganglia Glx levels and prefrontal GABA and Glx levels did not differ significantly between patient and control groups, but within the PD group prefrontal Glx levels correlated negatively with difficulties turning in bed. Results from an exploratory subgroup analysis indicate that the associations between GABA, Glx, and axial symptoms scores are typically more prominent in akinetic-rigid patients than in tremor-dominant patients. Conclusion: Alterations in GABAergic and glutamatergic neurotransmission may contribute to some of the axial symptoms of PD.
Mediation analysis for common binary outcomes

Mediation analysis provides an attractive causal inference framework to decompose the total effect of an exposure on an outcome into natural direct effects and natural indirect effects acting through a mediator. For binary outcomes, mediation analysis methods have been developed using logistic regression when the binary outcome is rare. These methods will not hold in practice when a disease is common. In this paper, we develop mediation analysis methods that relax the rare disease assumption when using logistic regression. We calculate the natural direct and indirect effects for common diseases by exploiting the relationship between logit and probit models. Specifically, we derive closed‐form expressions for the natural direct and indirect effects on the odds ratio scale. Mediation models for both continuous and binary mediators are considered. We demonstrate through simulation that the proposed method performs well for common binary outcomes. We apply the proposed methods to analyze the Normative Aging Study to identify DNA methylation sites that are mediators of smoking behavior on the outcome of obstructed airway function.
A family of neighborhood contingency logics

This article proposes the axiomatizations of contingency logics of various natural classes of neighborhood frames. In particular, by defining a suitable canonical neighborhood function, we give sound and complete axiomatizations of monotone contingency logic and regular contingency logic, thereby answering two open questions raised by Bakhtiari, van Ditmarsch, and Hansen. The canonical function is inspired by a function proposed by Kuhn in~1995. We show that Kuhn's function is actually equal to a related function originally given by Humberstone.
Perceived Usability, Desirability, and Workload of Mid-Air Gesture Control for Smart TVs

We explore in this work users’ perceived workload, desirability, and usability of selecting mid-air targets representing TV menu options anchored to physical loci in 3-D space. Toward this end, we introduce a gesture-based selection technique and a spatial user interface for Smart TVs that consists of shortcuts to TV channels located in mid-air in front of the user’s body. Target selection is implemented with pointing and hand gestures recognized with the Myo armband. Ten participants evaluated our prototype and were elicited for feedback. We report empirical results about perceived usability (SUS=77.8), desirability (high frequency of positive connotation words), and workload (TLX=43.9) of our gesture-based selection technique and spatial user interface and discuss future work directions.
Cardiorespiratory fitness is impaired and predicts mid‐term postoperative survival in patients with abdominal aortic aneurysm disease

What is the central question of this study? To what extent cardiorespiratory fitness is impaired in patients with abdominal aortic aneurysmal (AAA) disease and corresponding implications for postoperative survival requires further investigation. What is the main finding and its importance? Cardiorespiratory fitness is impaired in patients with AAA disease. Patients with peak oxygen uptake of <13.1 ml O2 kg−1 min−1 and ventilatory equivalent for carbon dioxide at anaerobic threshold ≥34 are associated with increased risk of postoperative mortality at 2 years. These findings demonstrate that cardiorespiratory fitness can predict mid‐term postoperative survival in AAA patients, which may help to direct care provision.
Real-time carbon allocation into biogenic volatile organic compounds (BVOCs) and respiratory carbon dioxide (CO2) traced by PTR-TOF-MS, 13CO2 laser spectroscopy and 13C-pyruvate labelling

Our understanding of biogenic volatile organic compound (BVOC) emissions improved substantially during the last years. Nevertheless, there are still large uncertainties of processes controlling plant carbon investment into BVOCs, of some biosynthetic pathways and their linkage to CO2 decarboxylation at central metabolic branching points. To shed more light on carbon partitioning during BVOC biosynthesis, we used an innovative approach combining δ13CO2 laser spectroscopy, high-sensitivity proton-transfer-reaction time-of-flight mass spectrometry and a multiple branch enclosure system in combination with position-specific 13C-metabolite labelling. Feeding experiments with position-specific 13C-labelled pyruvate, a central metabolite of BVOC synthesis, enabled online detection of carbon partitioning into 13C-BVOCs and respiratory 13CO2. Measurements of trace gas emissions of the Mediterranean shrub Halimium halimifolium revealed a broad range of emitted BVOCs. In general, [2-13C]-PYR was rapidly incorporated into emitted acetic acid, methyl acetate, toluene, cresol, trimethylbenzene, ethylphenol, monoterpenes and sesquiterpenes, indicating de novo BVOC biosynthesis of these compounds. In contrast, [1-13C]-pyruvate labelling substantially increased 13CO2 emissions in the light indicating C1-decarboxylation. Similar labelling patterns of methyl acetate and acetic acid suggested tightly connected biosynthetic pathways and, furthermore, there were hints of possible biosynthesis of benzenoids via the MEP-pathway. Overall, substantial CO2 emission from metabolic branching points during de novo BVOC biosynthesis indicated that decarboxylation of [1-13C]-pyruvate, as a non-mitochondrial source of CO2, seems to contribute considerably to daytime CO2 release from leaves. Our approach, combining synchronised BVOC and CO2 measurements in combination with position-specific labelling opens the door for real-time analysis tracing metabolic pathways and carbon turnover under different environmental conditions, which may enhance our understanding of regulatory mechanisms in plant carbon metabolism and BVOC biosynthesis.
Differential brain mechanisms for processing distracting information in task‐relevant and ‐irrelevant dimensions in visual search

A crucial function of our goal‐directed behavior is to select task‐relevant targets among distractor stimuli, some of which may share properties with the target and thus compete for attentional selection. Here, by applying functional magnetic resonance imaging (fMRI) to a visual search task in which a target was embedded in an array of distractors that were homogeneous or heterogeneous along the task‐relevant (orientation or form) and/or task‐irrelevant (color) dimensions, we demonstrate that for both (orientation) feature search and (form) conjunction search, the fusiform gyrus is involved in processing the task‐irrelevant color information, while the bilateral frontal eye fields (FEF), the cortex along the left intraparietal sulcus (IPS), and the left junction of intraparietal and transverse occipital sulci (IPTO) are involved in processing task‐relevant distracting information, especially for target‐absent trials. Moreover, in conjunction (but not in feature) search, activity in these frontoparietal regions is affected by stimulus heterogeneity along the task‐irrelevant dimension: heterogeneity of the task‐irrelevant information increases the activity in these regions only when the task‐relevant information is homogeneous, not when it is heterogeneous. These findings suggest that differential neural mechanisms are involved in processing task‐relevant and task‐irrelevant dimensions of the searched‐for objects. In addition, they show that the top‐down task set plays a dominant role in determining whether or not task‐irrelevant information can affect the processing of the task‐relevant dimension in the frontoparietal regions.
Methylation-derived Neutrophil-to-Lymphocyte Ratio and Lung Cancer Risk in Heavy Smokers

The neutrophil-to-lymphocyte ratio (NLR) is a biomarker that indicates systemic inflammation and can be estimated using array-based DNA methylation data as methylation-derived NLR (mdNLR). We assessed the relationship between prediagnosis mdNLR and lung cancer risk in a nested case–control study in the β-Carotene and Retinol Efficacy Trial (CARET) of individuals at high risk for lung cancer due to heavy smoking or substantial occupational asbestos exposure. We matched 319 incident lung cancer cases to controls based on age at blood draw, smoking, sex, race, asbestos, enrollment year, and time at risk. We computed mdNLR using the ratio of predicted granulocyte and lymphocyte proportions derived from DNA methylation signatures in whole blood collected prior to diagnosis (median 4.4 years in cases). Mean mdNLR was higher in cases than controls (2.06 vs. 1.86, P = 0.03). Conditional logistic regression models adjusted for potential confounders revealed a 21% increased risk of lung cancer per unit increase in mdNLR [OR 1.21; 95% confidence interval (CI) 1.01–1.45]. A 30% increased risk of non–small cell lung cancer (NSCLC) was observed for each unit increase in mdNLR (n = 240 pairs; OR 1.30, 95% CI, 1.03–1.63), and there was no statistically significant association between mdNLR and small-cell lung cancer risk. The mdNLR–NSCLC association was most pronounced in those with asbestos exposure (n = 42 male pairs; OR 3.39; 95% CI, 1.32–8.67). A better understanding of the role of mdNLR in lung cancer etiology may improve prevention and detection of lung cancer. Cancer Prev Res; 11(11); 727–34. ©2018 AACR.
Monovalent TNF receptor 1-selective antibody with improved affinity and neutralizing activity

ABSTRACT Selective inhibition of tumor necrosis factor (TNF) signaling through the proinflammatory axis of TNF-receptor 1 (TNFR1) while leaving pro-survival and regeneration-promoting signals via TNFR2 unaffected is a promising strategy to circumvent limitations of complete inhibition of TNF action by the approved anti-TNF drugs. A previously developed humanized antagonistic TNFR1-specific antibody, ATROSAB, showed potent inhibition of TNFR1-mediated cellular responses. Because the parental mouse antibody H398 possesses even stronger inhibitory potential, we scrutinized the specific binding parameters of the two molecules and revealed a faster dissociation of ATROSAB compared to H398. Applying affinity maturation and re-engineering of humanized variable domains, we generated a monovalent Fab derivative (13.7) of ATROSAB that exhibited increased binding to TNFR1 and superior inhibition of TNF-mediated TNFR1 activation, while lacking any agonistic activity even in the presence of cross-linking antibodies. In order to improve its pharmacokinetic properties, several Fab13.7-derived molecules were generated, including a PEGylated Fab, a mouse serum albumin fusion protein, a half-IgG with a dimerization-deficient Fc, and a newly designed Fv-Fc format, employing the knobs-into-holes technology. Among these derivatives, the Fv13.7-Fc displayed the best combination of improved pharmacokinetic properties and antagonistic activity, thus representing a promising candidate for further clinical development.
Adherence to oral chemotherapy: Challenges and opportunities

Purpose There is very little data on the effect of combining methods to better predict and improve oral antineoplastic adherence in cancer patients. The goal of this study was to evaluate the effectiveness of an intensive pharmacist intervention at the beginning of oral antineoplastic therapy versus nurse-led control group on adherence. Methods This was a prospective, randomized, open-label controlled trial performed in a single center hematology/oncology outpatient service to compare the effectiveness of repetitive pharmacist educational intervention on adherence rates measured at four and eight weeks after prescribing oral antineoplastic medication compared to a nurse-led control group. Both groups included investigator pill counts and self-report adherence questionnaires. Results Two-hundred patients were enrolled between 2009 and 2015. Fourteen of the 101 (14%) patients in the pharmacist group and 7 (7%) of the 99 patients in the nurse-led control group dropped out (p = 0.166). The majority of patients who remained in the study were 90–100% adherent to oral antineoplastic therapy in both groups. The pharmacist group slightly underperformed at Pill Count 2, possibly due to barriers for non-adherence. Statistically significant correlations associated with non-adherence were forgetfulness (p = 0.009), wanting to avoid side effects (p = 0.02), feeling depressed or overwhelmed (p = 0.032), or falling asleep before taking medication (p = 0.048) in both groups. Conclusion The combination of pill count and patient self-report adherence is a way of improving oral antineoplastic adherence. However, significant barriers to adherence were identified such as forgetfulness, wanting to avoid side effects, feeling depressed or overwhelmed, and falling asleep before taking medications.
The Relationship between Resilience with Self- Compassion, Social Support and Sense of Belonging in Women with Breast Cancer

Background: The purpose of this study was to investigate the associations among Resilience, self- compassion, social support and Sense of belonging in Iranian women with breast cancer. Materials and methods: This study was a descriptive-analytical cross-sectional study. The data of 150 patients with breast cancer were collected by convenience sampling using Demographic characteristics questionnaire, Connor-Davidson resilience scale, self-compassion scale and the multidimensional scale of perceived social support in Urmia, Iran in 2016. Results: The most age of the patients were in the range of 41-49 years, and most of them were married. The self- compassion, social support and Sense of belonging (r = all correlated significantly with resilience). Significant positive correlation was identified among self-compassion, social support, sense of belonging and resilience (P < 0.01). Conclusions: The results of this study clarified the self-compassion, social support and Sense of belonging are effective on the resilience among Iranian women with breast cancer. It is recommended to design some interventional programs to increase the aspect of resilience in these patients.
Dysregulated Network of Immune, Endocrine and Metabolic Markers is Associated to More Severe Human Chronic Chagas Cardiomyopathy

Individuals who are infected with Trypanosoma cruzi develop chronic Chagas cardiomyopathy (CCC), which is a complication involving a series of immune pathogenetic mechanisms, although an association between immune and metabolic alterations was more recently proposed. Accordingly, we investigated the immuno-metabolic response in chagasic patients and their possible influence on CCC pathogenesis. To this end, T. cruzi-seropositive (asymptomatic or with CCC) and sero-negative individuals were studied. Serum tumour necrosis factor (TNF)-α, interleukin (IL)-6, adipocytokines and the expression of their receptors in peripheral blood mononuclear cell (PBMC) were evaluated, together with other factors influencing the immune response. CCC patients showed major metabolic and hormonal abnormalities, in parallel with increased IL-6 and leptin serum levels. TNF-α receptor s, leptin and adiponectin receptors (ObR and Adipo-Rs respectively), as well as PPAR-γ expression in PBMCs from CCC patients were compatible with a counteracting response leading to an unfavourable immune-metabolic profile. These results suggest that persistently increased levels of immune-metabolic pro-inflammatory mediators along with the adverse endocrine anti-inflammatory response of CCC individuals, may contribute to the underlying mechanisms dealing with myocardial tissue damage.
Association of Polypharmacy With Mild Cognitive Impairment and Cognitive Ability: A Nationwide Survey in Taiwan.

BACKGROUND Polypharmacy, defined as the concomitant use of 5 or more medications, has a documented negative association with cognitive impairment such as delirium and is associated, potentially, with a higher risk of dementia. However, whether polypharmacy contributes to increased risk of mild cognitive impairment (MCI) or decreased cognitive capacity requires further investigation. This nationwide population survey investigated the association among polypharmacy, MCI, and dementia. METHODS Through random sampling based on the proportion of all Taiwan counties, subjects were recruited and received in-person interviews between December 2011 and March 2013. Demographic data and clinical information included medical histories, medication use, and mental status measured by the Taiwanese Mini-Mental State Examination (TMSE) and Clinical Dementia Rating (CDR). Data on lifestyle and habits were collected, and subjects were distributed to cognitively normal, MCI, or all-cause dementia groups based on criteria by the National Institute on Aging and the Alzheimer's Association. RESULTS A total of 7,422 people aged 65 years or older were recruited. After adjustment for age, sex, body mass index, education, medical comorbidities, and lifestyle and habits, polypharmacy was associated with a 1.75-fold increased odds of MCI and 2.33-fold increased odds of dementia. Polypharmacy was associated with a 0.51-point decrease in TMSE scores (P = .001) and a 0.10-point increase in CDR score (P < .001). Additionally, for those without specific vascular comorbidities, polypharmacy had a greatly more negative impact on cognitive capacity. CONCLUSIONS Polypharmacy is common in the elderly and is associated with significantly lower cognitive capacity and higher risks of MCI and dementia, especially for persons without diabetes, hypertension, hyperlipidemia, or cerebrovascular diseases.
Correlations Between Ultrasonographic Findings of Invasive Lobular Carcinoma of the Breast and Intrinsic Subtypes

Abstract Purpose To analyze the ultrasonographic findings of invasive lobular carcinoma (ILC) of the breast in 360 women and the correlations between the characteristics and the intrinsic subtypes. Materials and Methods We evaluated the imaging findings according to the lexicon of the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS). The included ultrasonographic features were shape, orientation, margin, echo pattern, posterior features, calcifications, the vascularity of the masses and the presence of architectural distortions. The associations between those features and the intrinsic ILC subtypes were investigated. Results The most common manifestations of ILC on ultrasound (US) were hypoechoic masses with irregular shape, parallel orientation, spiculated margin, posterior acoustic shadowing, no calcification and blood vessels in the rim. The patients in the luminal A subtype were the youngest, and the patients in the HER2 overexpression subtype were the oldest (p = 0.01). On US, the HER2 overexpression subtype was characterized by microlobulated margins (p = 0.002), while the luminal A subtype and the luminal B subtype mostly had spiculated margins. The basal-like subtype was distinctive in that it had no posterior features (p = 0.041), rather than acoustic shadowing, and the masses in the HER2 and basal-like subtypes were larger than in the other two groups (p = 0.03). Conclusion There were significant differences and several trends in the ultrasonographic characteristics of different intrinsic subtypes, which may supply accurate imaging diagnostic criteria to assist in the management of individuals with ILC.
Association of men's exposure to family planning programming and reported discussion with partner and family planning use: The case of urban Senegal

Background Family planning programs increasingly aim to encourage men to be involved in women’s reproductive health decision-making as well as support men to be active agents of change for their own and the couple’s reproductive health needs. This study contributes to this area of work by examining men’s exposure to family planning (FP) program activities in urban Senegal and determining whether exposure is associated with reported FP use and discussion of family planning with female partners. Methods This study uses data from two cross-sectional surveys of men in four urban sites of Senegal (Dakar, Pikine, Guédiawaye, Mbao). In 2011 and 2015, men ages 15–59 in a random sample of households from study clusters were approached and asked to participate in a survey about their fertility and family planning experiences. These data were used to determine the association between exposure to the Initiative Sénégalaise de Santé Urbaine (in English: Senegal Urban Reproductive Health Initiative) family planning program interventions with men’s reported modern family planning use and their reported discussion of FP with their partners. Since data come from the same study clusters at each time period, fixed effects methods at the cluster level allowed us to control for possible program targeting by geographic area. Results Multivariate models demonstrate that religious leaders speaking favorably about family planning, seeing FP messages on the television, hearing FP messages on the radio, and exposure to community outreach activities with a FP focus (e.g., house to house and community religious dialogues) are associated with reported modern family planning use and discussion of family planning with partners among men in the four urban sites of Senegal. Conclusions This study demonstrates that it is possible to reach men with FP program activities in urban Senegal and that these activities are positively associated with reported FP behaviors.
The functional morphology and possible taxonomic significance of the parapodia of the maldanid polychaetes Clymenella torquata and Euclymene oerstedi

The morphology of the chaetae of the maldanid polychaetes Clymenella torquata (Leidy) and Euclymene oerstedi (Claparède) (= Caesicirrus neglectus Arwidsson, '11) are described and related to movements observed in the laboratory. Graphs are constructed of the number and length of the neuropodial chaetae of each chaetiger throughout the body of Clymenella and of species of the genera Euclymene, Macroclymene and Axiothella, and show a characteristic and relatively constant pattern for each species. This work suggests that in making taxonomic decisions, more attention should be paid to the overall pattern of the neuropodial chaetae and less to the confusing distinction between aciculae and rostral uncini.