Miracle-dz/UniFAR-FTUs huggingface dataset:
Incomplete cortical reorganization in macular degeneration.

PURPOSE Activity in regions of the visual cortex corresponding to central scotomas in subjects with macular degeneration (MD) is considered evidence for functional reorganization in the brain. Three unresolved issues related to cortical activity in subjects with MD were addressed: Is the cortical response to stimuli presented to the preferred retinal locus (PRL) different from other retinal loci at the same eccentricity? What effect does the role of age of onset and etiology of MD have on cortical responses? How do functional responses in an MD subject's visual cortex vary for task and stimulus conditions? METHODS Eight MD subjects-four with age-related onset (AMD) and four with juvenile onset (JMD)-and two age-matched normal vision controls, participated in three testing conditions while undergoing functional magnetic resonance imaging (fMRI). First, subjects viewed a small stimulus presented at the PRL compared with a non-PRL control location to investigate the role of the PRL. Second, they viewed a full-field flickering checkerboard compared with a small stimulus in the original fovea to investigate brain activation with passive viewing. Third, they performed a one-back task with scene images to investigate brain activation with active viewing. RESULTS A small stimulus at the PRL generated more extensive cortical activation than at a non-PRL location, but neither yielded activation in the foveal cortical projection. Both passive and active viewing of full-field stimuli left a silent zone at the posterior pole of the occipital cortex, implying a lack of complete cortical reorganization. The silent zone was smaller in the task requiring active viewing compared with the task requiring passive viewing, especially in JMD subjects. CONCLUSIONS The PRL for MD subjects has more extensive cortical representation than a retinal region with matched eccentricity. There is evidence for incomplete functional reorganization of early visual cortex in both JMD and AMD. Functional reorganization is more prominent in JMD. Feedback signals, possibly associated with attention, play an important role in the reorganization.
Spontaneous peritonitis in critically ill cirrhotic patients: a diagnostic algorithm for clinicians and future perspectives

Spontaneous peritonitis (SP) is the most common infection among decompensated end-stage liver disease patients. SP is the infection of ascitic fluid (neutrophil ascitic count ≥250/mL) without an alternative focus of abdominal infection. According to the causative agent, clinicians can make the diagnosis of spontaneous bacterial peritonitis or spontaneous fungal peritonitis. The mortality rate is very high, ranging from one-fifth of the patients with spontaneous bacterial peritonitis to four-fifths of the patients with spontaneous fungal peritonitis. An immediate and accurate diagnosis can improve the outcome in end-stage liver disease patients. The aim of this work is to provide physicians with a practical diagnostic guidance for SP diagnosis according to current evidence, in order to improve the management of cirrhotic patients with infected ascitic fluid.
Prognostic significance of CD117 expression and TP53 missense mutations in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is extremely aggressive and associated with poor prognosis. There are no known predictive or prognostic markers for TNBC. Inhibition of tumor protein P53 (TP53) has been demonstrated to increase the levels of cluster of differentiation 117 (CD117) in human colorectal cancer cells. However, the function of TP53 in the regulation of CD117 in TNBC has, to the best of our knowledge, not been reported. In the present study, the association between the expression of CD117 protein and TP53 mutations was investigated, and their prognostic value in patients with TNBC was assessed. A total of 58 TNBC and 48 non-TNBC breast cancer tissue samples were assessed for the expression of CD117, p53 and TP53 mutations. The marker of proliferation Ki-67 (MKI67) proliferation index and vascular invasion index (obtained by measuring D2-40 and CD34) was investigated via immunohistochemistry, and mutations in exons 4–8 of TP53 were measured using direct sequencing. Associations between CD117 and p53 levels or TP53 mutations and clinical parameters were statistically evaluated. The rates of CD117 or MKI67 positivity, CD117+/TP53 missense mutation+, TP53 missense mutations or recurrence were significantly higher in patients with TNBC than in patients with non-TNBC. In TNBC tissues, the presence of CD117 was associated with TP53 missense mutations (P=0.031), vascular invasion, recurrence and MKI67. CD117+/TP53 missense mutation+ also associated with vascular invasion, recurrence and MKI67. Under univariate analysis, MKI67, vascular invasion, CD117, CD117+/TP53 missense mutation+ and TP53 missense mutations were associated with the overall survival of patients with TNBC. Multivariate analysis revealed that vascular invasion and CD117+/TP53 missense mutation+ in primary tumors were independent prognostic factors in patients with TNBC. In conclusion, CD117+/TP53 missense mutation+ was associated with MKI67, vascular invasion and tumor recurrence in TNBC. The presence of CD117 and TP53 missense mutations together in the primary tumors was an independent prognostic factor for survival of patients with TNBC.
An Approach for Receiver-Side Awareness Control in Vehicular Ad Hoc Networks

Vehicular Ad hoc networks (VANET) are a key element of cooperative intelligent transport systems. One of the challenges in VANETs is dealing with awareness and congestion due to the high amount of messages received from the vehicles in communication range. As VANETs are used in critical applications, congestion on the receiver side caused by the buffering of the packets is a safety hazard. In this paper, we propose a streamwise queuing system on the receiver side and show how it improves the timeliness of the messages received and maintains the awareness of the system in a congestion situation.
Autoinhibitory regulation of S100A8/S100A9 alarmin activity locally restricts sterile inflammation

Autoimmune diseases, such as psoriasis and arthritis, show a patchy distribution of inflammation despite systemic dysregulation of adaptive immunity. Thus, additional tissue-derived signals, such as danger-associated molecular patterns (DAMPs), are indispensable for manifestation of local inflammation. S100A8/S100A9 complexes are the most abundant DAMPs in many autoimmune diseases. However, regulatory mechanisms locally restricting DAMP activities are barely understood. We now unravel for the first time, to our knowledge, a mechanism of autoinhibition in mice and humans restricting S100-DAMP activity to local sites of inflammation. Combining protease degradation, pull-down assays, mass spectrometry, and targeted mutations, we identified specific peptide sequences within the second calcium-binding EF-hands triggering TLR4/MD2-dependent inflammation. These binding sites are free when S100A8/S100A9 heterodimers are released at sites of inflammation. Subsequently, S100A8/S100A9 activities are locally restricted by calcium-induced (S100A8/S100A9)2 tetramer formation hiding the TLR4/MD2-binding site within the tetramer interphase, thus preventing undesirable systemic effects. Loss of this autoinhibitory mechanism in vivo results in TNF-&agr;–driven fatal inflammation, as shown by lack of tetramer formation in crossing S100A9–/– mice with 2 independent TNF-&agr;–transgene mouse strains. Since S100A8/S100A9 is the most abundant DAMP in many inflammatory diseases, specifically blocking the TLR4-binding site of active S100 dimers may represent a promising approach for local suppression of inflammatory diseases, avoiding systemic side effects.
SKLB-23bb, A HDAC6-Selective Inhibitor, Exhibits Superior and Broad-Spectrum Antitumor Activity via Additionally Targeting Microtubules

Our previous study reported that SKLB-23bb, an orally bioavailable HDAC6-selective inhibitor, exhibited superior antitumor efficiency both in vitro and in vivo in comparison with ACY1215, a HDAC6-selective inhibitor recently in phase II clinical trial. This study focused on the mechanism related to the activity of SKLB-23bb. We discovered that despite having HDAC6-selective inhibition equal to ACY1215, SKLB-23bb showed cytotoxic effects against a panel of solid and hematologic tumor cell lines at the low submicromolar level. Interestingly, in contrast to the reported HDAC6-selective inhibitors, SKLB-23bb was more efficient against solid tumor cells. Utilizing HDAC6 stably knockout cell lines constructed by CRISPR–Cas9 gene editing, we illustrated that SKLB-23bb could remain cytotoxic independent of HDAC6 status. Investigation of the mechanism confirmed that SKLB-23bb exerted its cytotoxic activity by additionally targeting microtubules. SKLB-23bb could bind to the colchicine site in β-tubulin and act as a microtubule polymerization inhibitor. Consistent with its microtubule-disrupting ability, SKLB-23bb also blocked tumor cell cycle at G2–M phase and triggered cellular apoptosis. In solid tumor xenografts, oral administration of SKLB-23bb efficiently inhibited tumor growth. These results suggested that SKLB-23bb was an orally bioavailable HDAC6 and microtubule dual targeting agent. The microtubule targeting profile enhanced the antitumor activity and expanded the antitumor spectrum of SKLB-23bb, thus breaking through the limitation of HDAC6 inhibitors. Mol Cancer Ther; 17(4); 763–75. ©2018 AACR.
One-tailed asymptotic inferences for the difference of proportions: Analysis of 97 methods of inference

ABSTRACT Two-tailed asymptotic inferences for the difference d = p2 − p1 with independent proportions have been widely studied in the literature. Nevertheless, the case of one tail has received less attention, despite its great practical importance (superiority studies and noninferiority studies). This paper assesses 97 methods to make these inferences (test and confidence intervals [CIs]), although it also alludes to many others. The conclusions obtained are (1) the optimal method in general (and particularly for errors α = 1% and 5%) is based on arcsine transformation, with the maximum likelihood estimator restricted to the null hypothesis and increasing the successes and failures by 3/8; (2) the optimal method for α = 10% is a modification of the classic model of Peskun; (3) a more simple and acceptable option for large sample sizes and values of d not near to ±1 is the classic method of Peskun; and (4) in the particular case of the superiority and inferiority tests, the optimal method is the classic Wald method (with continuity correction) when the successes and failures are increased by one. We additionally select the optimal methods to make compatible the conclusions of the homogeneity test and the CI for d, both for one tail and for two (methods which are related to arcsine transformation and the Wald method).
Emotional Dissonance and Sickness Absence Among Employees Working With Customers and Clients: A Moderated Mediation Model via Exhaustion and Human Resource Primacy

Emotional dissonance, i.e., a discrepancy between required and felt emotions, has been established as a predictor of sickness absence in studies, but little is known about mechanisms that can explain this association. In order to prevent and reduce the impact of emotional dissonance on sickness absence, there is a need for greater attention to variables explaining when and how emotional dissonance is related to sickness absence. The overarching aim of this study was to examine whether emotional dissonance has an indirect association with sickness absence through exhaustion. In addition, we examined whether human resource primacy (HRP), which is the employer’s degree of concern for human resources, moderates this indirect effect. A sample of 7758 employees, all working with customers and clients, were recruited from 96 Norwegian organizations. Emotional dissonance, exhaustion, and HRP were measured through surveys and then linked to registry data on medically certified sickness absence for the year following the survey assessment. Results showed that exhaustion is a mediator for the relationship between emotional dissonance and sickness absence. Furthermore, higher levels of HRP were found to reduce the positive association between emotional dissonance and exhaustion, and the indirect effect of emotional dissonance on sickness absence through exhaustion is found to be weaker when HRP is high. By testing this moderated mediation model, the current study contributes to the literature on emotion work by clarifying mechanisms that are crucial for the development of targeted interventions that aim to reduce and prevent sickness absence in client-driven work environments.
Quadratic buck-boost converter with positive output-voltage and continuous input-current

Electrical power processing is an essential component of renewable energy sources such as PV panels and fuel cells conversion systems. The first stage of power conditioning usually consists of a DC-DC converter that enables a suitable DC bus voltage for a load feeder-or grid-tie-inverter. Motivated by the current needs in power conditioning of PEMFC systems, we propose a new power electronics converter. The proposed topology has a quadratic buck-boost voltage gain which allows a wide range of input voltages, providing a fixed output voltage with additional compelling features such as the circumvention of: the use of transformers, coupled inductors or extreme duty cycles. Moreover, the input current of the proposed converter is continuous and its output voltage is positive with respect to the input one, which is in sharp contrast with respect to other buck-boost topologies whose output voltages are in general negative. The main principles, steady-state analysis, and a small-signal model for the proposed circuit operating in continuous conduction mode (CCM) are presented in detail. Simulation and experimental results are provided to validate the theoretical analysis.
Mental health care treatment seeking among African Americans and Caribbean Blacks: what is the role of religiosity/spirituality?

ABSTRACT Objectives: As adults increase in age, the likelihood for using mental health care services decrease. Underutilization, expecially among racial/ethnic minorities such as African American and Caribbean Blacks, can result in a decrease in quality of life, as well as significant costs to families, employers, and health systems. Methods: The study explored the differences in relationships between mental health care usage and strength of religious/spiritual beliefs between African American and Caribbean Black older adults (54 years or older) and adults (18–53 years) using data from the National Survey of American Life (NSAL). Descriptive statistics and logistic regression analyses were conducted using Stata version 13.1. Results: Subjective ratings about the strength of religious/spiritual beliefs (OR = 1.26; 95 CI: 0.99, 1.61), age (OR = 0.62; 95 CI: 0.48, 0.81), and sex (OR = 1.59; 95 CI: 1.25, 2.02) were significantly associated with the odds of seeking mental health care. Additionally, persons living in the South were less likely to seek mental health care services (OR = 0.47; 95 CI: 0.37, 0.60). Conclusion: Strong religious/spiritual beliefs may promote mental health care usage. Future studies should examine the strength of religious/spiritual beliefs on mental health care usage among different demographic groups.
Adherence to oral anticoagulant therapy in secondary stroke prevention – impact of the novel oral anticoagulants

Background Oral anticoagulant therapy (OAT) potently prevents strokes in patients with atrial fibrillation. Vitamin K antagonists (VKA) have been the standard of care for long-term OAT for decades, but non-VKA oral anticoagulants (NOAC) have recently been approved for this indication, and raised many questions, among them their influence on medication adherence. We assessed adherence to VKA and NOAC in secondary stroke prevention. Methods All patients treated from October 2011 to September 2012 for ischemic stroke or transient ischemic attack with a subsequent indication for OAT, at three academic hospitals were entered into a prospective registry, and baseline data and antithrombotic treatment at discharge were recorded. At the 1-year follow-up, we assessed the adherence to different OAT strategies and patients’ adherence to their respective OAT. We noted OAT changes, reasons to change treatment, and factors that influence persistence to the prescribed OAT. Results In patients discharged on OAT, we achieved a fatality corrected response rate of 73.3% (n=209). A total of 92% of these patients received OAT at the 1-year follow-up. We observed good adherence to both VKA and NOAC (VKA, 80.9%; NOAC, 74.8%; P=0.243) with a statistically nonsignificant tendency toward a weaker adherence to dabigatran. Disability at 1-year follow-up was an independent predictor of lower adherence to any OAT after multivariate analysis, whereas the choice of OAT did not have a relevant influence. Conclusion One-year adherence to OAT after stroke is strong (>90%) and patients who switch therapy most commonly switch toward another OAT. The 1-year adherence rates to VKA and NOAC in secondary stroke prevention do not differ significantly between both therapeutic strategies.
Phase 1 trial of ibrutinib and carfilzomib combination therapy for relapsed or relapsed and refractory multiple myeloma

Abstract This phase 1, dose-finding study investigated ibrutinib and carfilzomib ± dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma (≥2 lines of therapy including bortezomib and an immunomodulatory agent). Of 43 patients enrolled, 74% were refractory to bortezomib and 23% had high-risk cytogenetics. No dose-limiting toxicities were observed. The recommended phase 2 dose was ibrutinib 840 mg and carfilzomib 36 mg/m2 with dexamethasone. The most common ≥ grade 3 (>10%) treatment-emergent adverse events were hypertension, anemia, pneumonia, fatigue, diarrhea, and thrombocytopenia. Overall response rate was 67% (very good partial response, 21%; stringent complete response, 2%), with an additional 9% minimal response. Median progression-free survival was 7.2 months and was not inferior in refractory nor high-risk patients. Median overall survival was not reached. Ibrutinib plus carfilzomib demonstrated encouraging responses with a manageable safety profile in this advanced population.
DeepMBS: Prediction of Protein Metal Binding-Site Using Deep Learning Networks

The tertiary structure of a protein indicates what vital function that protein fulfills in the cell. Prediction of the metal binding comformation of a protein from its sequence is a crucial step in predicting its tertiary structure. In this study, a computational method was developed for predicting the binding of Histidine and Cysteine to metals. We propose a deep convolutional neural network architecture, DeepMBS, to predict protein metal binding sites. To our knowledge, this study is the first realization of deep learning idea for the problem of predicting metal binding site. The method allows automatic extraction of complex interactions between important features using only sequence information by utilizing PAM120 scoring matrix. Features were extracted from protein sequences obtained from the Protein Data Bank and deep convolutional neural network was applied to these features. According to experimental results on a benchmark dataset, metal binding states can be predicted with 82% recall and 79% precision. These results show that a better performance can be achived with deep learning approach compared with previous studies on the same dataset.
Depression and appearance-related distress in functioning with lipedema

Abstract Lipedema is a chronic, progressive adipose tissue disorder that may impact the quality of life of women who suffer from it. The main aim of this study was to asses the role of perceived symptom severity, physical and psychological functioning with the disease in predicting quality of life in patients with lipedema. We conducted an online study with 329 participants who responded to five questionnaires measuring quality of life (World Health Organization Quality of Life BREF), lipedema symptom severity, mobility (Lower Extremity Functional Scale), depression (Patients Health Questionnaire-9), and appearance-related distress (Derriford Appearance Scale 24). Multiple hierarchical regression analyses showed that appearance-related distress and depression explained significantly more variance in quality of life when added to the symptom severity and mobility. Lower quality of life was predicted by higher symptom severity, lower mobility, higher appearance-related distress and higher depression severity. Appearance-related distress and depression constitute important aspects of psychological functioning in women with lipedema. Considering their relationship with quality of life, their assessment should be included in lipedema treatment with appropriate interventions aimed at decreasing appearance-related distress, as well as preventing and addressing depression.
Spatial Frequency Information Modulates Response Inhibition and Decision-Making Processes

We interact with the world through the assessment of available, but sometimes imperfect, sensory information. However, little is known about how variance in the quality of sensory information affects the regulation of controlled actions. In a series of three experiments, comprising a total of seven behavioral studies, we examined how different types of spatial frequency information affect underlying processes of response inhibition and selection. Participants underwent a stop-signal task, a two choice speed/accuracy balance experiment, and a variant of both these tasks where prior information was given about the nature of stimuli. In all experiments, stimuli were either intact, or contained only high-, or low- spatial frequencies. Overall, drift diffusion model analysis showed a decreased rate of information processing when spatial frequencies were removed, whereas the criterion for information accumulation was lowered. When spatial frequency information was intact, the cost of response inhibition increased (longer SSRT), while a correct response was produced faster (shorter reaction times) and with more certainty (decreased errors). When we manipulated the motivation to respond with a deadline (i.e., be fast or accurate), removal of spatial frequency information slowed response times only when instructions emphasized accuracy. However, the slowing of response times did not improve error rates, when compared to fast instruction trials. These behavioral studies suggest that the removal of spatial frequency information differentially affects the speed of response initiation, inhibition, and the efficiency to balance fast or accurate responses. More generally, the present results indicate a task-independent influence of basic sensory information on strategic adjustments in action control.
Population Dynamics of Lactobacillus helveticus in Swiss Gruyère-Type Cheese Manufactured With Natural Whey Cultures

Lactobacillus helveticus, a ubiquitous bacterial species in natural whey cultures (NWCs) used for Swiss Gruyère cheese production, is considered to have crucial functions for cheese ripening such as enhancing proteolysis. We tracked the diversity and abundance of L. helveticus strains during 6 months of ripening in eight Swiss Gruyère-type cheeses using a culture-independent typing method. The study showed that the L. helveticus population present in NWCs persisted in cheese and demonstrated a stable multi-strain coexistence during cheese ripening. With regard to proteolysis, one of the eight L. helveticus populations exhibited less protein degradation during ripening.