Miracle-dz/UniFAR-FTUs huggingface dataset:
Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab.

Baseline neutrophils and derived neutrophilto-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab P. F. Ferrucci1, P. A. Ascierto2, J. Pigozzo3, M. Del Vecchio4, M. Maio5, G. C. Antonini Cappellini6, M. Guidoboni7, P. Queirolo8, P. Savoia9, M. Mandalà10, E. Simeone2, S. Valpione3, M. Altomonte5, F. Spagnolo8, E. Cocorocchio1, S. Gandini11, D. Giannarelli12 & C. Martinoli1* Oncology of Melanoma Unit, European Institute of Oncology, Milan; Medical Oncology and Immunotherapy, Istituto Nazionale Tumori Fondazione ‘G. Pascale’, Naples; Melanoma Oncology Unit, Veneto Region Oncology Research Institute, Padua; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan; Istituto Toscano Tumori, University Hospital of Siena, Siena; IV Oncology Division, Istituto Dermopatico dell’Immacolata IRCCS, Rome; Immunotherapy and Somatic Cell Therapy Unit, Scientific Institute of Romagna, Meldola; Department of Medical Oncology, National Institute for Cancer Research, IRCCS San Martino, Genoa; Dermatologic Clinic, Department of Medical Sciences, University of Turin, Turin; Unit of Medical Oncology, Department of Oncology and Hematology, Papa Giovanni XXIII Hospital, Bergamo; Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan; Statistical Unit, Regina Elena National Cancer Institute, Rome, Italy
CYP2C9, CYP2C19 and CYP2D6 allele frequencies in the Ashkenazi Jewish population.

OBJECTIVE To determine and compare the cytochrome P450 (CYP)2C9, CYP2C19 and CYP2D6 allele and genotype frequencies in the Ashkenazi Jewish (AJ) population with other populations. METHODS CYP2C9, CYP2C19 and CYP2D6 genotypes were determined in 250 anonymous, unrelated, healthy AJ individuals from the greater New York (USA) metropolitan area. Genotyping was performed using the Tag-Ittrade mark Mutation Detection system and the recently redefined CYP2D6*41A allele was identified by a restriction fragment length polymorphism assay. RESULTS Among the 250 AJ individuals, the CYP2C9*1, *2, *3 and *5 allele frequencies were 0.772, 0.140, 0.086 and 0.002, respectively, and the genotypes were distributed into extensive- (60.8%), intermediate- (32.8%) and poor- (6.4%) metabolizer phenotypes. The CYP2C19*1, *2 and *4 allele frequencies were 0.830, 0.152 and 0.018, respectively, and the genotypes were distributed into extensive (69.2%), intermediate (27.6%) and poor (3.2%) metabolizers. The most common CYP2D6 alleles identified were *1, *2A, *4 and *41A, and their frequencies were 0.286 0.152 0.226 and 0.140, respectively. The CYP2D6 genotypes were distributed into ultrarapid- (8.8%), extensive- (70.0%), intermediate- (16.0%) and poor- (5.2%) metabolizer phenotypes. CONCLUSION Although the CYP2C9 allele and genotype frequencies in the AJ subjects were similar to those in other North American Caucasian populations, genotyping the CYP2C19*4 and CYP2D6*41A alleles in the AJ population resulted in the clinically relevant reclassification of the predicted metabolizer phenotypes. Inclusion of CYP2C19*4 reclassified individuals from either extensive- or intermediate- to the intermediate- or poor-metabolizer phenotypes, respectively. Inclusion of the redefined CYP2D6*41A allele increased the ultrarapid-, intermediate- and poor-metabolizer phenotype combined frequencies to 30%, indicating that approximately one in three AJ individuals may benefit from genotype-based drug selection and dosage. In addition, the ultrarapid CYP2D6 genotype frequency in the AJ population (8.8%) was approximately twofold higher than that in other North American Caucasians.
Multi-band CAP for Next-Generation Optical Access Networks Using 10-G Optics

40-Gb/s/λ multi-band carrierless amplitude and phase (CAP) modulation long-reach passive optical networks were demonstrated using 10-G class transceivers only. A major issue of multi-band CAP is that it is vulnerable to timing error, and this work has offered quantitative analysis about it in detail for the first time. A novel simple timing recovery approach, partial differential quadrature amplitude modulation constellation encoding and decoding schemes together with blind multimodulus algorithm equalization are proposed to address the issue efficiently, enabling zero-overhead signal recovery. Results show that it can offer excellent system tolerance to timing error of at least ±0.1 symbol period even for the highest frequency CAP sub-band. The characteristics of the transceiver are measured, and optimization of critical system parameters is performed including the CAP sub-band count, 10-G Mach–Zehnder intensity modulator operation conditions, optical launch power, and wavelength offset asymmetrical optical filtering. For downlink using erbium-doped fiber amplifier preamplifiers, successful 40-Gb/s multi-band CAP signal transmission over an 80-km (90-km) single-mode fiber is achieved with a link power budget of 33 dB (29 dB) considering a forward error correction threshold bit error ratio of 3.8 × 10−3.
Electrocardiographic and Hemodynamic Effects of Intravenous Infusion of Bupivacaine, Ropivacaine, Levobupivacaine, and Lidocaine In Anesthetized Ewes

Background and Objectives: Neural blockade techniques are associated with a risk of acute cardiac toxicity after accidental intravenous (IV) injection of local anesthetics. The aim of this study was to compare electrocardiographic (ECG) and hemodynamic (HEM) effects induced by IV infusion of local anesthetics in an anesthetized ewe model. Methods: Thirty-two anesthetized ewes received IV bupivacaine (BUPI), ropivacaine (ROPI), or levobupivacaine (S-BUPI) at an equimolar dose, or lidocaine (LIDO) at a 3-fold higher rate (n = 8 in each group). RR, PR, QRS, and QT intervals (QTc), changes (&Dgr;) in systolic and diastolic arterial pressure (SAP and DAP), and in myocardial contractility (dP/dt), were assessed every 30 seconds for 7 minutes. From main ECG variables (RR, PR, QRS, QT), we proposed to use multiple correspondence analysis and hierarchical ascending classification to explore the structure of statistical dependencies among those measurements, and to determine the different patterns of ECG and HEM changes induced by infusion of BUPI, ROPI, S-BUPI, and LIDO. Results: Graphic representation of multiple correspondence analysis associated BUPI with the most pronounced modifications in ECG and HEM variables, followed by in decreasing order ROPI, S-BUPI, and LIDO. Comparisons of clusters identified by hierarchical ascending classification confirmed this classification for ECG variables. Ventricular tachycardia occurred only in the BUPI group. Conclusions: In our anesthetized ewe model, high dose IV infusion of BUPI induced the most marked changes in RR, PR, QRS, QT, QTc intervals, &Dgr;SAP, and &Dgr;dP/dt. ROPI altered ECG variables less than BUPI but more than S-BUPI. LIDO was associated with the smallest changes.
Intrasession Repeatability and Interocular Symmetry of Foveal Avascular Zone and Retinal Vessel Density in OCT Angiography

Purpose To measure intrasession repeatability and interocular symmetry of the foveal avascular zone area (FAZA) and superficial retinal vessel density (SRVD) using AngioVue Analytics optical coherence tomography angiography (OCTA). Methods Fifty healthy individuals were prospectively enrolled. OCTA scans (3 × 3 and 6 × 6 mm) were acquired twice in right and once in left eyes. FAZA (with and without rescaling) and SRVD for 18 regions (whole, fovea, parafovea, six parafoveal subregions, and nine square zones) were compared between two scans in right eyes (repeatability) and between both eyes (symmetry). Coefficients of repeatability (CRs) and limits of agreement (LAs) were calculated. Results Axial length–based image size rescaling had negligible impact on the intrasession CR of FAZA in both 3 × 3- and 6 × 6-mm images. The intrasession CRs for the foveal SRVD were 3.3% and 6.1% in the 3 × 3- and 6 × 6-mm OCTA images, respectively. Age and axial length did not influence test–retest variability of FAZA or SRVD. The interocular LAs in FAZA (0.039–0.059 mm2) was comparable to its CR. However, the interocular LAs in foveal SRVD were −4.5% to +3.8%, with 13% of the cohort showing an interocular difference greater than the CR. Conclusions FAZA repeatability is not influenced by image size correction, and foveal SRVD is more variable in 6 × 6- than 3 × 3-mm OCTA images. Low image quality may contribute to interocular SRVD asymmetry. Translational Relevance CRs and LAs can be used to set a threshold for true changes in FAZA and SRVD in longitudinal studies of healthy individuals.
Maternal pertussis immunisation: clinical gains and epidemiological legacy

The increase in whooping cough (pertussis) incidence in many countries with high routine vaccination coverage is alarming, with incidence in the US reaching almost 50,000 reported cases per year, reflecting incidence levels not seen since the 1950s. While the potential explanations for this resurgence remain debated, we face an urgent need to protect newborns, especially during the time window between birth and the first routine vaccination dose. Maternal immunisation has been proposed as an effective strategy for protecting neonates, who are at higher risk of severe pertussis disease and mortality. However, if maternally derived antibodies adversely affect the immunogenicity of the routine schedule, through blunting effects, we may observe a gradual degradation of herd immunity. ‘Wasted’ vaccines would result in an accumulation of susceptible children in the population, specifically leading to an overall increase in incidence in older age groups. In this Perspective, we discuss potential long-term epidemiological effects of maternal immunisation, as determined by possible immune interference outcomes.
Leisure-time physical activity associates with cognitive decline

Objective: Because leisure-time physical activity (LTPA) is protective against incident dementia, we hypothesized that LTPA is protective against decline in domain-specific cognitive performance. Methods: As part of the Northern Manhattan Study, LTPA was ascertained at enrollment using a validated in-person questionnaire. We assessed cognition in participants in the Northern Manhattan Study MRI substudy using a standard neuropsychological examination (NPE) (n = 1,228), and a repeat examination was performed 5 years later (n = 876). LTPA was summarized as the maximum intensity of any activity performed, classified as none to light intensity (physical inactivity) (90%) vs moderate to heavy intensity (10%). The NPE was subcategorized using standardized z scores over validated domains: processing speed, semantic memory, episodic memory, and executive function. We used multivariable linear regression models to examine the association of LTPA with initial and change in cognitive performance. Analyses were adjusted for sociodemographics, cardiovascular disease risk factors, and MRI findings (white matter hyperintensity volume, silent brain infarcts, cerebral volume). Results: No/low levels of LTPA were associated with worse executive function, semantic memory, and processing speed scores on the first NPE. The associations were slightly attenuated and no longer significant after adjusting for vascular risk factors. Cognitively unimpaired participants reporting no/low LTPA vs moderate/high levels declined more over time in processing speed (β = −0.231 ± 0.112, p = 0.040) and episodic memory (β = −0.223 ± 0.117, p = 0.057) adjusting for sociodemographic and vascular risk factors. Conclusions: A low level of LTPA is independently associated with greater decline in cognitive performance over time across domains.
Failure to utilize feedback during explicit decision-making task in alcohol-dependent patients

Background: Patients who are diagnosed with alcohol-dependent syndrome (ADS) are shown to have neuropsychological deficits, especially executive function (EF) deficits. Among the EFs, decision-making is one such function which has consistently been shown to be impaired in people who are dependent on alcohol, compared to controls. Decision-making in this population is usually assessed with gambling-type tasks. However, some of these tasks are ambiguous, work on chance factors, rarely match with real-life gambling situations, and/or involve nonconscious mechanisms. Materials and Methods: The current study compared 26 male patients with ADS (P-ADS) with equal number of their nonalcohol-dependent male siblings on sensation seeking and explicit gambling task (EGT). EGT is similar to the Iowa gambling task in administration, but varies from it as it involves a single outcome and provides unambiguous, explicit, and continuous feedback for the participants. Results and Conclusion: The results did not show any significant relationship between decision-making variables and sensation seeking. However, despite unambiguous, explicit, and continuous feedback, patients showed significantly poor decision-making as compared to the siblings of the P-ADS group. This study throws light on why people who are addicted to alcohol have difficulties in decision-making, despite knowing the adverse effects.
Clearance of human papillomavirus infection after successful conization in patients with cervical intraepithelial neoplasia

The natural history of high‐risk human papillomavirus (HRHPV) infection after successful treatment of cervical intraepithelial neoplasia (CIN) is not well known. This study was performed to evaluate the rate and pattern of HRHPV infection clearance after successful conization for CIN and to analyze factors associated with such clearance. A total of 287 patients who underwent loop electrosurgical excision procedures (LEEP) owing to HRHPV‐associated CIN were included. All patients had negative resection margins on LEEP specimens and underwent HPV testing with the hybrid capture II system at 3‐, 6‐, 9‐, 12‐, 18‐ and 24‐month follow‐up visits after LEEP. Persistent HPV infections were detected in 45.6%, 14.3%, 6.3%, 2.2%, 1.5% and 1.1% of patients at 3, 6, 9, 12, 18 and 24 months after LEEP, respectively. Clearance rates did not differ by age, parity or severity of cervical lesion. However, clearance rates were significantly slower in patients with HPV DNA loads >500 RLU/PC before LEEP (p = 0.040). During 2 years of follow‐up after LEEP, 24 patients had recurrent disease revealed by biopsy. The odds ratios for recurrent disease in patients with persistent HRHPV infection increased gradually from 5.17 at the 3‐month follow‐up visit to 12.54, 15.69 and 25.90 at 6‐, 9‐, 12‐ and 24‐month follow‐up visits, respectively. We conclude that HRHPV infection cleared gradually in most patients within 6 months of treatment. Clearance rates were significantly slower in patients with HPV DNA loads >500 RLU/PC. Persistent HPV infection was a significant positive predictor of recurrence.
Brain comorbidities in normal pressure hydrocephalus

This cross‐sectional study aims to compare gait changes after the cerebrospinal fluid (CSF) tap test between normal pressure hydrocephalus patients with and without brain comorbidities (NPH+ and NPH− respectively) and then to identify significant contributors to a poor CSF tap test amongst individuals with NPH+.
Frequency and characteristics of different clinical phenotypes of chronic obstructive pulmonary disease.

SETTING Clinical phenotypes of chronic obstructive pulmonary disease (COPD) identify patients with common characteristics. OBJECTIVES To investigate the distribution of four different COPD phenotypes: non-exacerbators, patients with asthma-COPD overlap syndrome (ACOS), exacerbators with chronic bronchitis and those without, we analysed the impact of COPD on quality of life (HRQoL), and on anxiety and depression in these phenotypes. DESIGN Observational, multicentre study conducted among 3125 COPD patients recruited from out-patient clinics in Barcelona, Spain. Phenotyping was performed based on the clinical information available. The COPD Assessment Test and EuroQoL-5 Dimensions questionnaire were used to evaluate HRQoL; patient mood was evaluated using the Hospital Anxiety and Depression Scale (HADS). RESULTS The distribution of phenotypes was as follows: 60.6% non-exacerbators, 15.9% ACOS patients, 19.3% exacerbators with chronic bronchitis and 4.3% exacerbators without chronic bronchitis. Non-exacerbators had milder COPD, whereas exacerbators presented with the most severe disease, with little difference between those with and those without chronic bronchitis. ACOS patients were more frequently female with better lung function, but more impaired HRQoL and greater anxiety and depression, than non-exacerbators. CONCLUSIONS Almost two thirds of COPD patients are non-exacerbators, and 15.9% have ACOS. Different phenotypes showed different demographic and clinical characteristics as well as impact on HRQoL and mood.
A direct XFEM formulation for modeling of cohesive crack growth in concrete

Applying a direct formulation for the enrichment of the displacement field an extended finite element (XFEM) scheme for modeling of cohesive crack growth is developed. Only elements cut by the crack is enriched and the scheme fits within the framework of standard FEM code. The scheme is implemented for the 3-node constant strain triangle (CST) and the 6-node linear strain triangle (LST). Modeling of standard concrete test cases such as fracture in the notched three point beam bending test (TPBT) and in the four point shear beam test (FPSB) illustrates the performance. The XFEM results show good agreement with results obtained by applying standard interface elements in FEM and with experimental results. In conjunction with criteria for crack growth local versus nonlocal computation of the crack growth direction is discussed.
Generalizations of tournaments: A survey

We survey results concerning various generalizations of tournaments. The reader will see that tournaments are by no means the only class of directed graphs with a very rich structure. We describe, among numerous other topics mostly related to paths and cycles, results on hamiltonian paths and cycles. The reader will see that although these problems are polynomially solvable for all of the classes described, they can be highly nontrivial, even for these “tournament-like” digraphs. © 1998 John Wiley & Sons, Inc. J. Graph Theory 28: 171–202, 1998
Towards the implementation of first-order temporal resolution: the expanding domain case

First-order temporal logic is a concise and powerful notation, with many potential applications in both Computer Science and Artificial Intelligence. While the full logic is highly complex, recent work on monodic first-order temporal logics has identified important enumerable and even decidable fragments. In this paper, we develop a clausal resolution method for the monodic fragment of first-order temporal logic over expanding domains. We first define a normal form for monodic formulae and then introduce novel resolution calculi that can be applied to formulae in this normal form. We state correctness and completeness results for the method. We illustrate the method on a comprehensive example. The method is based on classical first-order resolution and can, thus, be efficiently implemented.
Saliency detection by forward and backward cues in deep-CNN

As prior knowledge of objects or object features helps us make relations for similar objects on attentional tasks, pre-trained deep convolutional neural networks (CNNs) can be used to detect salient objects on images regardless of the object class is in the network knowledge or not. In this paper, we propose a top-down saliency model using CNN, a weakly supervised CNN model trained for 1000 object labelling task from RGB images. The model detects attentive regions based on their objectness scores predicted by selected features from CNNs. To estimate the salient objects effectively, we combine both forward and backward features, while demonstrating that partially-guided backpropagation will provide sufficient information for selecting the features from forward run of CNN model. Finally, these top-down cues are enhanced with a state-of-the-art bottom-up model as complementing the overall saliency. As the proposed model is an effective integration of forward and backward cues through objectness without any supervision or regression to ground truth data, it gives promising results compared to state-of-the-art models in two different datasets.
Predict Responsibly: Increasing Fairness by Learning To Defer

Machine learning systems, which are often used for high-stakes decisions, suffer from two mutually reinforcing problems: unfairness and opaqueness. Many popular models, although generally accurate, cannot express uncertainty about their predictions. Even in regimes where a model is inaccurate, users may trust the model's predictions too fully, and allow its biases to reinforce the user's own. In this work, we explore models that learn to defer. In our scheme, a model learns to classify accurately and fairly, but also to defer if necessary, passing judgment to a downstream decision-maker such as a human user. We further propose a learning algorithm which accounts for potential biases held by decision-makers later in a pipeline. Experiments on real-world datasets demonstrate that learning to defer can make a model not only more accurate but also less biased. Even when operated by highly biased users, we show that deferring models can still greatly improve the fairness of the entire pipeline.
Increased frequency of circulating Th22 cells in patients with B-cell non-Hodgkin's lymphoma

T helper (Th) 22 cells play important roles in the pathogenesis of autoimmune and inflammatory diseases, and their function in tumors remains uncertain. In the current study, we investigated the alternations and clinical significance of circulating Th22 cells in patients with B-cell non-Hodgkin's lymphoma (B-NHL). We found that the frequency of Th22 cells was significantly elevated in peripheral blood of newly-diagnosed B-NHL patients, and returned to normal level after chemotherapy. In consistent with increased Th22 frequency, plasma IL-22 and IL-6 levels in B-NHL patients were remarkably increased. Moreover, the increased Th22 frequency was associated with the older age (> 60 yr) and a poorer response to therapy in B-NHL patients. In addition, there existed a statistically positive correlation between circulating Th22 and Th17 frequencies in B-NHL patients. Our data demonstrated that circulating Th22 frequency was associated with the clinical outcome and prognosis of B-NHL patients, indicating that Th22 immune response might play an important role in the development and progression of B-NHL.