Miracle-dz/UniFAR-FTUs huggingface dataset:
Towards clinically more relevant dissection of patient heterogeneity via survival‐based Bayesian clustering

Motivation Discovery of clinically relevant disease sub‐types is of prime importance in personalized medicine. Disease sub‐type identification has in the past often been explored in an unsupervised machine learning paradigm which involves clustering of patients based on available‐omics data, such as gene expression. A follow‐up analysis involves determining the clinical relevance of the molecular sub‐types such as that reflected by comparing their disease progressions. The above methodology, however, fails to guarantee the separability of the sub‐types based on their subtype‐specific survival curves. Results We propose a new algorithm, Survival‐based Bayesian Clustering (SBC) which simultaneously clusters heterogeneous‐omics and clinical end point data (time to event) in order to discover clinically relevant disease subtypes. For this purpose we formulate a novel Hierarchical Bayesian Graphical Model which combines a Dirichlet Process Gaussian Mixture Model with an Accelerated Failure Time model. In this way we make sure that patients are grouped in the same cluster only when they show similar characteristics with respect to molecular features across data types (e.g. gene expression, mi‐RNA) as well as survival times. We extensively test our model in simulation studies and apply it to cancer patient data from the Breast Cancer dataset and The Cancer Genome Atlas repository. Notably, our method is not only able to find clinically relevant sub‐groups, but is also able to predict cluster membership and survival on test data in a better way than other competing methods. Availability and implementation Our R‐code can be accessed as https://github.com/ashar799/SBC. Contact ashar@bit.uni‐bonn.de Supplementary information Supplementary data are available at Bioinformatics online.
The Influence of Smoking on the Variations in Carboxyhemoglobin and Methemoglobin During Urologic Surgery

Introduction: Surgery is supposed to modulate the production of carbon monoxide by the reduction of heme oxygenase activity or transcriptional regulation of inducible heme oxygenase. On the other hand, the inhalation of tobacco smoke can substantially raise the level of carboxyhemoglobin in the blood. Furthermore, methemoglobin is maintained at a constant level. However, excessive production of methemoglobin relative to total methemoglobin reductase activity results in methemoglobin increase. Aim: The aim of our study was to investigate the perioperative variations of carboxyhemoglobin and methemoglobin during urologic surgeries, and at the same time to evaluate the changes in methemoglobin as a possible indicator of nitric oxide generation. Our second aim was to evaluate the effect of preoxygenation on the level of carboxyhemoglobin and methemoglobin and the influence of blood transfusion on their changes. Material and methods: The study included 30 patients scheduled for urologic surgery under general endotracheal anesthesia, aged 18–60 years without any history of respiratory disease, divided into two groups. The study group comprised patients who were smoking cigarettes or tobacco pipe, while the control group included non-smokers. In both groups carboxyhemoglobin (COHb) and methemoglobin (MetHb) levels were determined preoperatively, after preoxygenation, and postoperatively. Results: COHb levels were decreased postoperatively in both groups. The average values of COHb between the two groups were statistically significantly different (p=0.00). MetHb levels increased postoperatively in the group of smokers and decreased in the group of non-smokers. There were no statistically significant differences in the average postoperative MetHb levels between the two groups. Conclusion: Changes in carboxyhemoglobin and methemoglobin concentrations in arterial blood occur during urologic surgery, although these amplitudes are small when compared with carbon monoxide intoxication and methemoglobinemia. It is likely that organ perfusion and functions are affected by these monoxide gas mediators during urologic surgery.
A tutorial on computational classical logic and the sequent calculus

Abstract We present a model of computation that heavily emphasizes the concept of duality and the interaction between opposites–production interacts with consumption. The symmetry of this framework naturally explains more complicated features of programming languages through relatively familiar concepts. For example, binding a value to a variable is dual to manipulating the flow of control in a program. By looking at the computational interpretation of the sequent calculus, we find a language that lets us speak about duality, control flow, and evaluation order in programs as first-class concepts. We begin by reviewing Gentzen's LK sequent calculus and show how the Curry–Howard isomorphism still applies to give us a different basis for expressing computation. We then illustrate how the fundamental dilemma of computation in the sequent calculus gives rise to a duality between evaluation strategies: strict languages are dual to lazy languages. Finally, we discuss how the concept of focusing, developed in the setting of proof search, is related to the idea of type safety for computation expressed in the sequent calculus. In this regard, we compare and contrast two different methods of focusing that have appeared in the literature, static and dynamic focusing, and illustrate how they are two means to the same end.
The Evolutionary Enigma of Mixed Mating Systems in Plants: Occurrence, Theoretical Explanations, and Empirical Evidence

▪ Abstract Mixed mating, in which hermaphrodite plant species reproduce by both self- and cross-fertilization, presents a challenging problem for evolutionary biologists. Theory suggests that inbreeding depression, the main selective factor opposing the evolution of selfing, can be purged with self-fertilization, a process that is expected to yield pure strategies of either outcrossing or selfing. Here we present updated evidence suggesting that mixed mating systems are frequent in seed plants. We outline the floral and pollination mechanisms that can lead to intermediate outcrossing, review the theoretical models that address the stability of intermediate outcrossing, and examine relevant empirical evidence. A comparative analysis of estimated inbreeding coefficients and outcrossing rates suggests that mixed mating often evolves despite strong inbreeding depression. The adaptive significance of mixed mating has yet to be fully explained for any species. Recent theoretical and empirical work suggests that.
Category, Letter, and Emotional Verbal Fluency in Spanish–English Bilingual Speakers: A Preliminary Report

Objective The purpose of this study was to compare the performance of bilingual speakers on an emotional verbal fluency task to category and letter verbal fluency tasks. A second purpose was to compare performances on these tasks to language proficiency ratings. Method Twelve verbal fluency tasks were administered to 21 Spanish-English bilingual speakers. Results were analyzed for differences between fluency types (category, letter, and emotional) and languages (English and Spanish). Results Participants generated the most items in category fluency tasks and the least items in emotional fluency tasks. The number of items generated for letter and emotional fluency tasks were not significantly different, but both were significantly lower than the number of items generated in category fluency. More items were generated for positive emotions than for negative emotions. Differences between languages for category and letter fluency tasks were significantly correlated with differences in language proficiency ratings, but this finding was not found for emotional fluency tasks. Conclusions Self-ratings of proficiency and language dominance correlated significantly with performance on category and letter fluency tasks and may be useful predictors of differences between languages on these tasks. Emotional fluency was not significantly correlated with language proficiency ratings, suggesting that performance on emotional fluency may be more significantly affected by emotional processing ability. The emotional verbal fluency task has potential as a component of neuropsychological evaluations to screen easily and quickly for emotional processing deficits, including those associated with traumatic brain injury and depression. Additionally, results support a positivity bias in language and cognition processes.
Current Evidence for Clinical Efficacy of Platelet Rich Plasma in Aesthetic Surgery: A Systematic Review

Background Platelet rich plasma (PRP) has attracted attention in a number of surgical fields due to a wide variety of potential clinical benefits. Yet PRP has not gained wide popularity in aesthetic surgery as a result of uncertainty surrounding objective clinical evidence. Objectives We aim to describe the current applications, define preparation and activation, explore effectiveness, and propose a classification system to facilitate comparisons across studies. Methods A comprehensive review of the literature regarding the use of platelet rich plasma in aesthetic surgery was performed. Data gathered included: PRP application, study type, subject number, centrifugation, anticoagulation, activation, PRP composition, and outcomes. Results Thirty-eight reports were identified. Applications included injection into aging skin (29%), scalp alopecia (26%), lipofilling (21%), fractional laser (13%), and facial surgery (11%). The majority of studies (53%) were case series without controls. Leucocytes were sparsely defined (32%). The concentration of injected and/or baseline platelets was rarely clarified (18%). The mechanism of activation was described in 27 studies (71%), while anticoagulation was uncommonly elucidated (47%). While most studies (95%) claim effectiveness, objective measures were only utilized in 17 studies (47%). Conclusions Current studies produce context-dependent results with a lack of consistent reporting of PRP preparation, composition, and activation in aesthetic applications, making meaningful meta-analysis unrealistic. Thus the method of PRP preparation warrants increased attention. We recommend a set of descriptors, FIT PAAW (described below), to produce scientifically grounded conclusions, facilitating a clearer understanding of the situations in which PRP is effective. Level of Evidence 4
Genetic Polymorphism and Bottleneck Analysis of Balkhi, Hashtnagri, and Michni Sheep Populations Using Microsatellite Markers

ABSTRACT Pakistan is rich in sheep genetic resources. Balkhi, Hashtnagri, and Michni are neighboring sheep populations found in Khyber Pakhtunkhwa province of Pakistan. In this study, we analyzed the genetic structures and bottleneck incidents within these sheep populations using 31 microsatellite DNA markers. Total numbers of 116, 100, and 95 alleles, with average numbers of 3.20, 3.26, and 3.74 alleles per locus were observed, respectively, in Balkhi, Hashtnagri, and Michni population. Mean observed heterozygosity was 0.402 in Balkhi, 0.416 in Hashtnagri, and 0.522 in Michni population. All the three sheep populations showed significantly high inbreeding. Michni population was found to be in mutation drift equilibrium, showing the absence of genetic bottleneck. The data of Balkhi and Hashtnagri indicated the presence of genetic bottleneck in these populations. These results suggest a moderate level of genetic diversity within Michni population that may be useful for breed improvement programs. Hashtnagri and Balkhi populations having low within breed genetic variability may contain some valuable characteristics that need to be conserved.
Hyperinsulinemia and Insulin Resistance in Dopamine &bgr;-Hydroxylase Deficiency

Context Dopamine β-hydroxylase (DBH) deficiency is a rare genetic disorder characterized by failure to convert dopamine to norepinephrine. DBH-deficient patients lack sympathetic adrenergic function and are therefore predisposed to orthostatic hypotension. DBH-deficient mice exhibit hyperinsulinemia, lower plasma glucose levels, and insulin resistance due to loss of tonic sympathetic inhibition of insulin secretion. The impact of DBH deficiency on glucose homeostasis in humans is unknown. Case Description We describe the metabolic profile of an adolescent female DBH-deficient patient. The patient underwent genetic testing, cardiovascular autonomic function testing, and evaluation of insulin secretion and sensitivity with hyperglycemic clamp under treatment-naive conditions. All procedures were repeated after 1 year of treatment with the norepinephrine prodrug droxidopa (300 mg, 3 times a day). Genetic testing showed a homozygous mutation in the DBH gene (rs74853476). Under treatment-naive conditions, she had undetectable plasma epinephrine and norepinephrine levels, resulting in sympathetic noradrenergic failure and orthostatic hypotension (-32 mm Hg supine to seated). She had high adiposity (41%) and fasting plasma insulin levels (25 μU/mL), with normal glucose (91 mg/dL). Hyperglycemic clamp revealed increased glucose-stimulated insulin secretion and insulin resistance. Droxidopa restored plasma norepinephrine and improved orthostatic tolerance, with modest effects on glucose homeostasis. Conclusions We provide evidence for impairment in cardiovascular autonomic regulation, hyperinsulinemia, enhanced glucose-stimulated insulin secretion, and insulin resistance in a DBH-deficient patient. These metabolic derangements were not corrected by chronic droxidopa treatment. These findings provide insight into the pathophysiology and treatment of DBH deficiency and into the importance of catecholaminergic mechanisms to resting metabolism.
Effect of sterilisation and storage conditions on the migration of bisphenol A from tinplate cans of the Lebanese market

ABSTRACT The use of bisphenol A (BPA) in lacquer coating of food cans has been restricted by different authorities in many countries, such as in Europe. However, such regulation does not exist in many other countries including Lebanon. Due to the lack of data on the quality of Lebanese can production; this study investigates the migration of BPA from two types of tinplate cans manufactured in Lebanon, before and after sterilisation. Cans were analysed under different storage conditions (time and temperature) and filled with an aqueous simulant. The determination of BPA was carried out using UPLC with fluorescence detection, and further confirmed by MS detection. After sterilisation BPA levels drastically increased from an average of 0.15 to 109 µg/kg, giving a BPA migration around 10.5 µg/dm2 for both types of cans. Storage temperature and time had no significant influence on BPA levels in sterilised cans (p-value > 0.05); however, these factors significantly affected BPA levels in non-sterilised cans.
Identification of a five B cell-associated gene prognostic and predictive signature for advanced glioma patients harboring immunosuppressive subtype preference

High grade gliomas contribute to most brain tumor mortality. A few studies reported that the immune system affected glioma development, and immune biomarkers helped understand the disease and formulate effective immunotherapy for patients. Currently, no B lymphocyte-based prognostic signature was reported in gliomas. By applying 78 B cell lineage-specific genes, we conducted a whole-genome gene expression analysis in 782 high grade gliomas derived from three independent datasets by Cox regression analysis and risk score method for signature identification, and then used Gene Ontology, Gene Set Enrichment Analysis, and other statistical methods for functional annotations of the signature-defined differences. We developed a five B cell-associated gene signature for prognosis of high grade glioma patients, which is independent of clinicopathological and genetic features. The signature identified high risk patients suitable for chemoradiotherapy, whereas low risk patients should rule out chemotherapy with radiotherapy only. We found that tumors of TCGA Mesenchymal subtype and wild type IDH1 were preferentially stratified to the high risk group, which bore strong immunosuppressive microenvironment, while tumors of TCGA Proneural subtype and mutated IDH1 were significantly accumulated to the low risk group, which exhibited less immunosuppressive state. The five B cell-associated gene signature predicts poor survival of high risk patients bearing strong immunosuppression and helps select optimal therapeutic regimens for glioma patients.
Tunable selective receiver front end with impedance transformation filtering

A highly selective impedance transformation filtering technique suitable for tunable selective RF receivers is presented in this paper. To achieve blocker rejection comparable with surface acoustic wave (SAW) filters, we use a two‐stage architecture based on a low‐noise transconductance amplifier (LNTA). The filter rejection is captured by a linear periodically varying model that includes band limitation by the LNTA output impedance and the related parasitic capacitances of the impedance transformation circuit. This model is also used to estimate ‘back folding’ by interferers placed at harmonic frequencies. Discussed is also the effect of thermal noise folding and phase noise on the circuit noise figure. As a proof of concept, a chip design of a tunable RF front end using 65 nm complementary metal‐oxide‐semiconductor (CMOS) technology is presented. In measurements, the circuit achieves blocker rejection competitive to SAW filters with noise figure 3.2–5.2 dB, out of band IIP3 > +17 dBm, and blocker P1dB > +5 dBm over frequency range of 0.5–3 GHz. Copyright © 2015 John Wiley & Sons, Ltd.
Albuminuria Changes and Cardiovascular and Renal Outcomes in Type 1 Diabetes: The DCCT/EDIC Study.

BACKGROUND AND OBJECTIVES In trials of people with type 2 diabetes, albuminuria reduction with renin-angiotensin system inhibitors is associated with lower risks of cardiovascular events and CKD progression. We tested whether progression or remission of microalbuminuria is associated with cardiovascular and renal risk in a well characterized cohort of type 1 diabetes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We studied 1441 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Albumin excretion rate (AER) was quantified annually or biennially for up to 30 years. For each participant, albuminuria status was defined over time as normoalbuminuria (AER continuously <30 mg/d), sustained microalbuminuria (AER, 30-299 mg/d on two consecutive visits), macroalbuminuria (AER≥300 mg/d), or remitted microalbuminuria (transition from sustained microalbuminuria to AER<30 mg/d on two consecutive visits). We tested associations of time-updated albuminuria status with adjudicated clinical cardiovascular events, the development of reduced GFR (<60 ml/min per 1.73 m2 on two consecutive visits), and subclinical cardiovascular disease. RESULTS At least one cardiovascular event occurred in 184 participants, and 98 participants developed reduced eGFR. Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were each associated with higher risk of cardiovascular events (adjusted hazard ratios [HRs] and 95% confidence intervals [95% CIs]: 1.79 [1.13 to 2.85], 2.62 [1.68 to 4.07], and 2.65 [1.68 to 4.19], respectively) and reduced eGFR (adjusted HRs [95% CIs], 5.26 [2.43 to 11.41], 4.36 [1.80 to 10.57], and 54.35 [30.79 to 95.94], respectively). Compared with sustained microalbuminuria, remission to normoalbuminuria was not associated with reduced risk of cardiovascular events (adjusted HR, 1.33; 95% CI, 0.68 to 2.59) or reduced eGFR (adjusted HR, 1.75; 95% CI, 0.56 to 5.49). Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were associated with greater carotid intima-media thickness, and macroalbuminuria was associated with a greater degree of coronary artery calcification. CONCLUSIONS In type 1 diabetes, microalbuminuria and macroalbuminuria are associated with higher risks of cardiovascular disease and reduced eGFR, but achieving a remission of established microalbuminuria to normoalbuminuria does not appear to improve outcomes.
Authenticated and efficient key management for wireless ad hoc networks

In this paper we present a key management protocol for wireless ad hoc multi-hop networks. Two objectives were crucial in our design: (1) distributed trust to ensure robustness, and (2) strong authentication to prevent the battery drain attack. We achieve distributed trust by presenting a hierarchical and distributed public key infrastructure for ad hoc networks. Our PKI has been designed to map onto hierarchical ad hoc networks, while maintaining global connectivity and flexibility. If a misbehavior detection scheme is present on the network, then the security of our PKI can be improved through collaboration with this scheme. Next to this PKI we propose a mechanism to securely establish and maintain link keys between the dierent
On the stability and dynamics of stochastic spiking neuron models: Nonlinear Hawkes process and point process GLMs

Point process generalized linear models (PP-GLMs) provide an important statistical framework for modeling spiking activity in single-neurons and neuronal networks. Stochastic stability is essential when sampling from these models, as done in computational neuroscience to analyze statistical properties of neuronal dynamics and in neuro-engineering to implement closed-loop applications. Here we show, however, that despite passing common goodness-of-fit tests, PP-GLMs estimated from data are often unstable, leading to divergent firing rates. The inclusion of absolute refractory periods is not a satisfactory solution since the activity then typically settles into unphysiological rates. To address these issues, we derive a framework for determining the existence and stability of fixed points of the expected conditional intensity function (CIF) for general PP-GLMs. Specifically, in nonlinear Hawkes PP-GLMs, the CIF is expressed as a function of the previous spike history and exogenous inputs. We use a mean-field quasi-renewal (QR) approximation that decomposes spike history effects into the contribution of the last spike and an average of the CIF over all spike histories prior to the last spike. Fixed points for stationary rates are derived as self-consistent solutions of integral equations. Bifurcation analysis and the number of fixed points predict that the original models can show stable, divergent, and metastable (fragile) dynamics. For fragile models, fluctuations of the single-neuron dynamics predict expected divergence times after which rates approach unphysiologically high values. This metric can be used to estimate the probability of rates to remain physiological for given time periods, e.g., for simulation purposes. We demonstrate the use of the stability framework using simulated single-neuron examples and neurophysiological recordings. Finally, we show how to adapt PP-GLM estimation procedures to guarantee model stability. Overall, our results provide a stability framework for data-driven PP-GLMs and shed new light on the stochastic dynamics of state-of-the-art statistical models of neuronal spiking activity.