Miracle-dz/UniFAR-FTUs huggingface dataset:
Multigene mutational profiling of cholangiocarcinomas identifies actionable molecular subgroups

One-hundred-fifty-three biliary cancers, including 70 intrahepatic cholangiocarcinomas (ICC), 57 extrahepatic cholangiocarcinomas (ECC) and 26 gallbladder carcinomas (GBC) were assessed for mutations in 56 genes using multigene next-generation sequencing. Expression of EGFR and mTOR pathway genes was investigated by immunohistochemistry. At least one mutated gene was observed in 118/153 (77%) cancers. The genes most frequently involved were KRAS (28%), TP53 (18%), ARID1A (12%), IDH1/2 (9%), PBRM1 (9%), BAP1 (7%), and PIK3CA (7%). IDH1/2 (p=0.0005) and BAP1 (p=0.0097) mutations were characteristic of ICC, while KRAS (p=0.0019) and TP53 (p=0.0019) were more frequent in ECC and GBC. Multivariate analysis identified tumour stage and TP53 mutations as independent predictors of survival. Alterations in chromatin remodeling genes (ARID1A, BAP1, PBRM1, SMARCB1) were seen in 31% of cases. Potentially actionable mutations were seen in 104/153 (68%) cancers: i) KRAS/NRAS/BRAF mutations were found in 34% of cancers; ii) mTOR pathway activation was documented by immunohistochemistry in 51% of cases and by mutations in mTOR pathway genes in 19% of cancers; iii) TGF-ß/Smad signaling was altered in 10.5% cancers; iv) mutations in tyrosine kinase receptors were found in 9% cases. Our study identified molecular subgroups of cholangiocarcinomas that can be explored for specific drug targeting in clinical trials.
Polyphenolic Compounds as Pancreatic Lipase Inhibitors

Abstract Obesity and its associated diseases such as diabetes mellitus and coronary heart diseases are a major challenge for our society. An important target for the treatment of obesity includes the development of inhibitors of nutrient digestion and absorption. Inhibition of pancreatic lipase and the associated reduction of lipid absorption is an attractive approach for the discovery of potent agents. Currently, the only clinically approved pharmacologic agent as pancreatic lipase inhibitor is Orlistat. However, its usage is compromised by unpleasant gastrointestinal adverse reactions (oily stools, oily spotting, flatulence). The use of botanical materials as a potential source of new drugs is of increasing importance and application. Natural products that are interesting for obesity treatment are generally considered to have less toxic and side effects than totally synthetic drugs. One of the most important sources of potential pancreatic lipase inhibitors represents the class of polyphenols. This article summarizes most studied subclasses of polyphenols including flavonoids, hydroxycinnamic acids, hydroxybenzoic acids and lignans with pancreatic lipase inhibitory effects. A structural comparison of potent inhibitors shows an increased inhibitory effect depending on number and position of phenolic hydroxyl groups, degree of polymerization and elimination of glycosylation during digestion.
A Maximum Principle for Partial Information Backward Stochastic Control Problems with Applications

This paper studies the partial information control problems of backward stochastic systems. There are three major contributions made in this paper: (i) First, we obtain a new stochastic maximum principle for partial information control problems. Our method relies on a direct calculation of the derivative of the cost functional. (ii) Second, we introduce two classes of partial information linear-quadratic backward control problems for the first time and then investigate them using the maximum principle. Complete and explicit solutions are obtained in terms of some forward and backward stochastic differential filtering equations. (iii) Last but not least, we study a class of full information stochastic pension fund optimization problems which can be viewed as a special case of our general partial information ones. Applying the aforementioned maximum principle, we derive the optimal contribution policy in closed-form and present some related economic remarks.
Muscimol Diffusion after Intracerebral Microinjections: A Reevaluation Based on Electrophysiological and Autoradiographic Quantifications

Intracerebral muscimol injection is widely used to inactivate discrete brain structures during behavioral tasks. However, little effort has been made to quantify the extent of muscimol diffusion. The authors report here electrophysiological and autoradiographic results obtained after muscimol injection (1 microg/microl) either into the nucleus basalis magnocellularis (0.1-0.4 microl) or into the thalamic reticular nucleus (RE, 0.05-0.1 microl). In 52 rats, multiunit recordings were collected either in the RE or in the auditory thalamus during the 2 h following muscimol injection. Decreases in neuronal activity were observed up to 3 mm from the injection site; their time of occurrence was a function of the distance between the injection and recording sites. Because these decreases cannot be explained by physiological effects, they likely reflected muscimol diffusion up to the recording sites. Autoradiographic studies involved 25 rats and different experimental conditions. Optical density (OD) measures indicated that after a survival time of 15 min, a 0.05 microl injection produced a labeled area of 5.25 mm(2) at the injection site and a rostrocaudal labeling of 1.7 mm. Increasing the survival time to 60 min, or increasing the injected volume to 0.1 microl, systematically led to a larger labeled area at the injection site (8-12 mm(2)) and to a larger rostrocaudal diffusion (2.0-2.5 mm). Direct quantifications of radioactivity by a high-resolution radioimager validated the OD measures and even indicated a larger muscimol diffusion (up to 3.25 mm). Thus, these data point out that muscimol diffusion after intracerebral microinjection is larger than usually supposed. The relationships between these results and those obtained in behavioral studies are discussed.
A flow measure of missing women by age and disease

The existing literature on 'missing women' suggests that the problem is mostly concentrated in India and China, and mostly related to sex-selective abortions and neglect of female children. In a recent paper in the Review of Economic Studies, Anderson and Ray (AR) develop a new ‘flow’ measure of missing women in developing countries by comparing actual age-sex-specific mortality rates with 'expected' ones. Contrary to the existing literature on missing women, they, and the World Bank which subsequently followed this method, find that gender bias in mortality is much larger than previously found (4Ͳ5 million excess female deaths per year), is as severe among adults as it is among children in India, is larger in Sub-Saharan Africa than in China and India, and was a massive problem in the US around 1900.We show that the data for Sub-Saharan Africa used by AR are generated by simulations in ways that deliver the findings on Africa (and the US in 1900) by construction. We also show that the findings are entirely dependent on a highly implausible reference standard from rich countries that is inappropriately applied to settings in developing countries; the attempt to control for differences in the disease environment does not correct for this problem and fails basic plausibility checks. When a more appropriate reference standard is used, most of the new findings of AR disappear, the extent of gender bias in mortality is much smaller (though still substantial). JEL codes: J16, D63, I10
DeepXplore: Automated Whitebox Testing of Deep Learning Systems

Deep learning (DL) systems are increasingly deployed in safety- and security-critical domains including self-driving cars and malware detection, where the correctness and predictability of a system's behavior for corner case inputs are of great importance. Existing DL testing depends heavily on manually labeled data and therefore often fails to expose erroneous behaviors for rare inputs. We design, implement, and evaluate DeepXplore, the first whitebox framework for systematically testing real-world DL systems. First, we introduce neuron coverage for systematically measuring the parts of a DL system exercised by test inputs. Next, we leverage multiple DL systems with similar functionality as cross-referencing oracles to avoid manual checking. Finally, we demonstrate how finding inputs for DL systems that both trigger many differential behaviors and achieve high neuron coverage can be represented as a joint optimization problem and solved efficiently using gradient-based search techniques. DeepXplore efficiently finds thousands of incorrect corner case behaviors (e.g., self-driving cars crashing into guard rails and malware masquerading as benign software) in state-of-the-art DL models with thousands of neurons trained on five popular datasets including ImageNet and Udacity self-driving challenge data. For all tested DL models, on average, DeepXplore generated one test input demonstrating incorrect behavior within one second while running only on a commodity laptop. We further show that the test inputs generated by DeepXplore can also be used to retrain the corresponding DL model to improve the model's accuracy by up to 3%.
Prescribed exercise: a prospective study of health-related quality of life and physical fitness among participants in an officially sponsored municipal physical training program.

BACKGROUND Participants who completed a 3-month prescribed individualized exercise program in groups were followed-up prospectively. The aims were to describe the characteristics of the participants, their health-related quality of life (HRQoL) and physical fitness at baseline, at completion and at 12-month follow-up, and to identify predictors of HRQoL and physical fitness at completion and at 12-month follow-up. METHODS A 1-group follow-up design was used. Data were collected from records of 163 attendees at a municipality-sponsored health center in Norway. HRQoL was measured by self-report using the COOP/WONCA questionnaire. Physical fitness was estimated from the results of a 2-km walk test. RESULTS Of the 163 participants referred to the clinic, 130 (79.8%) were women and 33 were (20.2%) men. Participants who completed were older than those who dropped out. The participants showed clinical improvement in physical fitness and all health-related quality life domains (d > 0.53) at the completion of the program and in physical functioning, mental health, performance of daily activities, overall health, and perceived improved health after 12 months (d > 0.36). CONCLUSIONS Participation in group-based prescribed exercise program for 3 months may improve physical fitness and HRQoL significantly in short and long terms.
Maternal Birth Outcomes: Processes and Challenges in Anambra State, Nigeria

The views of nurse experts and policymakers on maternal birth outcomes in Anambra State, Nigeria, were explored using qualitative content analysis. The findings indicate that although there are different levels of birth attendants in Anambra State, nurses attend to most deliveries; are highly favored; and are the most trusted obstetric providers among skilled personnel. Obstetric complications are extensive, leading to high mortality and morbidity. Poverty, gender inequity, and weak health systems—encompassing insufficiency of trained nursing workforce among other issues—intensify poor maternal birth outcomes.
Shear Wave Velocity-Penetration Resistance Correlation for Holocene and Pleistocene Soils of an Area in Central Italy

With the aim of preventing and reducing the seismic risk in an area in Umbria, central Italy, of notable importance from a historic and economic point of view, the local government of the Umbria Region promoted a considerable seismic microzonation project. A widespread geotechnical investigation survey was carried out to this end, including sounding with undisturbed sampling, standard penetration tests, dynamic cone penetration tests, cone penetration tests, down-hole and cross-hole tests. The purposes of this paper are to summarise the results from field and laboratory testing performed to identify the main soil types detected in the area and to provide some empirical relations to estimate shear wave velocity from cone penetration resistance for the most representative geological formations of the region. With the aim of obtaining relationships that are as reliable as possible, the available data were carefully selected. Moreover, as it is well known that larger coefficients of determination are generally obtained when soil type, geologic age and sedimentary environment effects are considered in the regression equations, the selected data were subdivided and attributed to the two main geological units (Holocene and Pleistocene) present in the area. For each of these, grain size was classified using CPT data and two soil types (fine and coarse grained soils) were therefore identified. Regional correlations between shear wave velocity and penetration resistance parameters were thus assessed for all the four previously defined soil classes and for the two geological units without distinguishing fine-grained and coarse-grained soils. The proposed relationships were compared with those suggested in the geotechnical literature by different authors and their predictive capacity was finally checked by comparing VS values estimated by means of the correlations and those measured in geophysical survey (cross-hole and down-hole tests). The results of these comparisons are also shown in this paper.
Biopsy Findings in Renal Allograft Dysfunction in a Live Related Renal Transplant Program

Background: There is little information in literature on renal allograft biopsy findings in renal allograft dysfunction in live related renal transplant recipients. Material and Methods: A retrospective review of 1210 renal allograft biopsies from 575 renal transplant patients was carried out over a period of seven years from June 1997 till December 2004. The demographic, clinical, laboratory and biopsy findings were collected and analyzed. Results: A total of 1210 graft biopsies were performed on 575 patients. The mean age of recipients and donors was 29.2±9.7 years, and 35.7±10.5 years, respectively. The males were predominant among recipients (76.7 vs. 23.3%), while among donors they only slightly outnumbered females (51.8 vs. 48.2%). Regarding pathological lesions, acute rejection was seen in 292 (24%) cases, followed by acute tubular injury and cyclosporine A (CsA) toxicity, found in 281 (23.2%) and 134 (11%) cases respectively. Chronic allograft nephropathy (CAN) with variable degree of tubular atrophy was seen in 361 (29.8%) cases. Seventy nine cases (6.5%) of acute pyelonephritis were detected on graft biopsies. A number of rare lesions were also found, including 13 (1.07%) cases of recurrent/de novo renal disease, and 13 (1.07%) of polyoma virus infection. Five cases of CsA induced hemolytic uremic syndrome (HUS) were also noted. Conclusion: In conclusion, the incidence of acute rejection is low in our patients as compared to cadaveric renal transplant recipients as reported in Western studies and CsA toxicity is more common. Recurrent/de novo renal disease is uncommon in our patients.
Noise resilient 2-DoF washout tracking controller for nanopositioning systems subject to sensor drift

We propose a two-degree-of-freedom washout control structure for tracking of sinusoidal references in lightly damped structures subject to sensor drift and measurement noise. An algorithm is derived, assigning stable parameter intervals to a second-order washout damping compensator for a resonant plant with a single dominant mode. Simulation results demonstrate quality drift and noise rejection performance of the proposed method, when tracking a 3 kHz sinusoidal reference in a nanopositioning stage with a 4.5 kHz resonance frequency. Experiments are conducted, validating high efficacy of the proposed washout tracking control strategy.
The atomic norm formulation of OSCAR regularization with application to the Frank-Wolfe algorithm

This paper proposes atomic norm formulation of octagonal shrinkage and clustering algorithm for regression (OSCAR) regularization. The OSCAR regularizer can be reformulated using a decreasing weighted sorted ℓ1 (DWSL1) norm (which is shown to be convex). We also show how, by exploiting an atomic norm formulation, the Ivanov regularization scheme involving the OSCAR regularizer can be handled using the Frank-Wolfe (also known as conditional gradient) method.
A unified approach to input-output encoding for FSM state assignment

A new theoretical formulation of the output encoding and state assignment targeting two-level logic implementations is presented. The formulation is based on a uniform representation of the input and output constraints. This allows to solve the input and output encoding problems, inherent in state assignment of FSM, simultaneously. The solution is based on the concept of dichotomy and graph coloring.
Maternal modulation of growth hormone secretion in the neonatal rat: involvement of mother-offspring interactions.

Serum GH levels increased in 2- or 8-day-old rat pups when sucking mammary glands whose main milk ducts were ligated. Although intragastric administration of rat milk has been shown to increase serum GH levels in neonatal rats, ingestion of milk during suckling did not increase serum GH values further. In another experiment, 2-day-old pups obtained no milk when they were suckled by anaesthetized mothers, and in this instance the serum GH concentration of the pups decreased. This decrease was prevented if the mothers were injected with oxytocin to counteract the depressant effect of the anaesthesia on milk ejection; nevertheless, GH levels in neonatal animals failed to increase following suckling. Thus some aspect of maternal activity appears to be involved in the suckling-induced increase of serum GH in rat pups. To elucidate which components of maternal activity might be involved, the effects of manipulations of ambient temperature as well as stimulation of the oral or anogenital regions were examined. Exposing rat pups to 37 degrees C (nest temperature) during the 6-h separation period before suckling prevented the separation-induced decrease in serum GH levels of 2-day-old pups. Moreover, exposure to 37 degrees C for 30 min following a 6-h separation at room temperature (22 degrees C) mimicked the effect of suckling in increasing serum GH levels in the pups. Suckling following separation at 37 degrees C was unable to increase serum GH values further. (ABSTRACT TRUNCATED AT 250 WORDS)
Augmented Renal Vancomycin Clearance in Cancer Patients: A Case Report and Review of the Literature

Background: Bacterial infections are a major cause of morbidity and mortality in cancer patients. Particularly diagnostic and therapeutic procedures (e.g. central venous catheters, paracentesis) increase the risk of infections in this immunocompromised patient population. In the past, antibiotic therapy was empirically initiated in these patients, guided by treatment regimens designed for patients without malignancy; however, the hyperdynamic circulation in systemic inflammatory response syndrome, as well as the presence of malignancy itself, may have a crucial impact on treatment success. Case Report: Here, we report the case of a 55-year-old patient with advanced pancreatic cancer and Staphylococcus epidermidis bacteremia who, due to increased renal vancomycin clearance, required treatment with high doses of vancomycin in order to reach therapeutic trough levels. Conclusion: Oncological status can be a cofactor of altered pharmacokinetics in terms of a paraneoplastic syndrome. With the help of this case report we want to call attention to this clinically significant phenomenon with its inherent risk of inefficient antibiotic treatment.
Human Factors of the Confirmation Bias in Intelligence Analysis: Decision Support From Graphical Evidence Landscapes

Objective: This study addresses the human factors challenge of designing and validating decision support to promote less biased intelligence analysis. Background: The confirmation bias can compromise objectivity in ambiguous medical and military decision making through neglect of conflicting evidence and judgments not reflective of the entire evidence spectrum. Previous debiasing approaches have had mixed success and have tended to place additional demands on users' decision making. Method: Two new debiasing interventions that help analysts picture the full spectrum of evidence, the relation of evidence to a hypothesis, and other analysts' evidence assessments were manipulated in a repeated-measures design: (a) an integrated graphical evidence layout, compared with a text baseline; and (b) evidence tagged with other analysts' assessments, compared with participants' own assessments. Twenty-seven naval trainee analysts and reservists assessed, selected, and prioritized evidence in analysis vignettes carefully constructed to have balanced supporting and conflicting evidence sets. Bias was measured for all three evidence analysis steps. Results: A bias to select a skewed distribution of confirming evidence occurred across conditions. However, graphical evidence layout, but not other analysts' assessments, significantly reduced this selection bias, resulting in more balanced evidence selection. Participants systematically prioritized the most supportive evidence as most important. Conclusion: Domain experts exhibited confirmation bias in a realistic intelligence analysis task and apparently conflated evidence supportiveness with importance. Graphical evidence layout promoted more balanced and less biased evidence selection. Application: Results have application to real-world decision making, implications for basic decision theory, and lessons for how shrewd visualization can help reduce bias.
Quantum Computers Speed Up Classical with Probability Zero

Let $f$ denote length preserving function on words. A classical algorithm can be considered as $T$ iterated applications of black box representing $f$, beginning with input word $x$ of length $n$. It is proved that if $T=O(2^{n/(7+e)}), e >0$, and $f$ is chosen randomly then with probability 1 every quantum computer requires not less than $T$ evaluations of $f$ to obtain the result of classical computation. It means that the set of classical algorithms admitting quantum speeding up has probability measure zero. The second result is that for arbitrary classical time complexity $T$ and $f$ chosen randomly with probability 1 every quantum simulation of classical computation requires at least $\Omega (\sqrt {T})$ evaluations of $f$.
An Observer-Based Optimal Voltage Control Scheme for Three-Phase UPS Systems

This paper proposes a simple optimal voltage control method for three-phase uninterruptible-power-supply systems. The proposed voltage controller is composed of a feedback control term and a compensating control term. The former term is designed to make the system errors converge to zero, whereas the latter term is applied to compensate for the system uncertainties. Moreover, the optimal load current observer is used to optimize system cost and reliability. Particularly, the closed-loop stability of an observer-based optimal voltage control law is mathematically proven by showing that the whole states of the augmented observer-based control system errors exponentially converge to zero. Unlike previous algorithms, the proposed method can make a tradeoff between control input magnitude and tracking error by simply choosing proper performance indexes. The effectiveness of the proposed controller is validated through simulations on MATLAB/Simulink and experiments on a prototype 600-VA testbed with a TMS320LF28335 DSP. Finally, the comparative results for the proposed scheme and the conventional feedback linearization control scheme are presented to demonstrate that the proposed algorithm achieves an excellent performance such as fast transient response, small steady-state error, and low total harmonic distortion under load step change, unbalanced load, and nonlinear load with the parameter variations.