Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring the epigenetic drug discovery landscape

ABSTRACT Introduction: Epigenetic modification has been implicated in a wide range of diseases and the ability to modulate such systems is a lucrative therapeutic strategy in drug discovery. Areas covered: This article focuses on the concepts and drug discovery aspects of epigenomics. This is achieved by providing a survey of the following concepts: (i) factors influencing epigenetics, (ii) diseases arising from epigenetics, (iii) epigenetic enzymes as druggable targets along with coverage of existing FDA-approved drugs and pharmacological agents, and (iv) drug repurposing/repositioning as a means for rapid discovery of pharmacological agents targeting epigenetics. Expert opinion: Despite significant interests in targeting epigenetic modifiers as a therapeutic route, certain classes of target proteins are heavily studied while some are less characterized. Thus, such orphan target proteins are not yet druggable with limited report of active modulators. Current research points towards a great future with novel drugs directed to the many complex multifactorial diseases of humans, which are still often poorly understood and difficult to treat.
A simple method for obtaining large deformation of IPMC actuators utilizing copper tape

The response of ionic polymer–metal composite (IPMC) actuator varies by the counter ion. This paper shows findings that copper ion can be exchanged as the counter ion simply by applying voltage through the copper–metal contacts attached to IPMC, and also shows that the copper-ion-exchanged IPMC exhibits much larger deformation than the tetraethylammonium(TEA)-ion-exchanged IPMC. The responses of three different counter ions, sodium, TEA, and copper that are exchanged by aqueous solutions are firstly shown as the reference experiment. The proposed method that uses copper tape for exchanging copper ion is then shown with various conditions of the applied voltage. Graphical Abstract
Simulation of Geographical Trends in the Chowdhury Ecosystem Model

The Chowdhury model for ecosystems is modified by assuming a birth rate increasing with temperature, and additional minor changes. Its computer simulation based on individual births and deaths gives a biodiversity increasing from cold to warm climates. Complexity of foodwebs increases with time and at a higher rate at low latitudes, and there is a higher rate of species creation at low latitudes. Keeping many niches empty makes the results correspond more closely to natural gradients. All these findings are in good agreement with theoretical predictions and empirical findings, demonstrating that the Chowdhury model used for our simulations realistically reflects these.
Recent developments on treatment strategies and the prognosis of dermatomyositis: a review

Abstract Dermatomyositis is an autoimmune disease affecting both skin and muscle. Steroids are the first line treatment. However, no consensus regarding dosing, length of treatment, tapering speed, or when to add which immunosuppressant in case of steroid resistance, has been reached, as randomized-controlled trials are scarce. Especially data on long-term treatment is lacking in order to decide on the most effective treatment for long-term remission. Empiric evidence suggests that with an initially aggressive treatment with oral steroids followed by a slow taper, during which disease activity is adequately controlled, patients can be off therapy within typically 24–48 months, and remain disease-free without medication for over 20 years. Biologics such as rituximab have shown good results in the treatment of refractory DM. New, targeted therapies have been reported to improve DM in single cases or case series, but have to be evaluated for efficacy in randomized controlled trials.
Open questions in the theory of semifeasible computation

The study of semifeasible algorithms was initiated by Selman's work a quarter of century ago [Sel79,Sel81,Sel82]. Informally put, this research stream studies the power of those sets L for which there is a deterministic (or in some cases, the function may belong to one of various nondeterministic function classes) polynomial-time function f such that when at least one of x and y belongs to L, then f(x, y) ∈ L ∩ {x, y}. The intuition here is that it is saying: "Regarding membership in L, if you put a gun to my head and forced me to bet on one of x or y as belonging to L, my money would be on f(x, y) . "In this article, we present a number of open problems from the theory of semifeasible algorithms. For each we present its background and review what partial results, if any, are known.
Cannabis Use and Cognition in Schizophrenia

People with schizophrenia frequently report cannabis use, and cannabis may be a risk factor for schizophrenia, mediated through effects on brain function and biochemistry. Thus, it is conceivable that cannabis may also influence cognitive functioning in this patient group. We report data from our own laboratory on the use of cannabis by schizophrenia patients, and review the existing literature on the effects of cannabis on cognition in schizophrenia and related psychosis. Of the 23 studies that were found, 14 reported that the cannabis users had better cognitive performance than the schizophrenia non-users. Eight studies reported no or minimal differences in cognitive performance in the two groups, but only one study reported better cognitive performance in the schizophrenia non-user group. Our own results confirm the overall impression from the literature review of better cognitive performance in the cannabis user group. These paradoxical findings may have several explanations, which are discussed. We suggest that cannabis causes a transient cognitive breakdown enabling the development of psychosis, imitating the typical cognitive vulnerability seen in schizophrenia. This is further supported by an earlier age of onset and fewer neurological soft signs in the cannabis-related schizophrenia group, suggesting an alternative pathway to psychosis.
Effect of alginate supplementation on weight loss in obese subjects completing a 12-wk energy-restricted diet: a randomized controlled trial.

BACKGROUND Acute studies with alginate-based preloads suggested that these strong gelling fibers may induce increased feelings of satiety and reduce energy intakes. However, the long-term efficacy and safety of alginate supplementation on body weight regulation are lacking. OBJECTIVE The primary aim of the study was to investigate the effects in subjects of alginate supplementation in conjunction with energy restriction (-300 kcal/d) on loss of body weight and fat and, second, on metabolic risk markers in comparison with in a placebo group. DESIGN In a parallel, double-blind, placebo-controlled study, we randomly assigned 96 obese subjects to either an energy-restricted diet plus a placebo preload supplement or an energy-restricted diet plus an alginate-based preload supplement (15 g fiber). The preload was administered as a beverage 3 times/d before main meals for a period of 12 wk. RESULTS No differences in loss of body weight and fat between groups were shown in the intension-to-treat (ITT) analysis (P > 0.1). However, in the completer analysis (n = 80), we showed a greater weight loss with alginate (6.78 ± 3.67 kg) than with the placebo (5.04 ± 3.40 kg) (P = 0.03), which was mainly attributed to a reduction in the percentage of body fat (P = 0.03). In the ITT analysis, a larger decrease in systolic and diastolic blood pressure was shown in the placebo group than in the alginate group (P < 0.05). Plasma concentrations of glucose, insulin, C-reactive protein, and ghrelin, HOMA-IR, and lipid metabolism did not differ between treatment groups in the ITT analysis (P > 0.1). CONCLUSION These results suggest that alginate supplementation as an adjunct to energy restriction may improve weight loss in obese subjects who complete a 12-wk dietary intervention.
Diagnostic Accuracy and Clinical Utility of Noninvasive Testing for Coronary Artery Disease

BACKGROUND Computed tomography coronary angiography (CTCA) has become a popular noninvasive test for diagnosing coronary artery disease. OBJECTIVE To compare the accuracy and clinical utility of stress testing and CTCA for identifying patients who require invasive coronary angiography (ICA). DESIGN Observational study. SETTING University medical center in Rotterdam, the Netherlands. PATIENTS 517 patients referred by their treating physicians for evaluation of chest symptoms by using stress testing or ICA. INTERVENTION Stress testing and CTCA in all patients. MEASUREMENTS Diagnostic accuracy of stress testing and CTCA compared with ICA; pretest probabilities of disease by Duke clinical score; and clinical utility of noninvasive testing, defined as a pretest or posttest probability that suggests how to proceed with testing (no further testing if < or =5%, proceed with ICA if between 5% and 90%, and refer directly for ICA if > or =90%). RESULTS Stress testing was not as accurate as CTCA; CTCA sensitivity approached 100%. In patients with a low (<20%) pretest probability of disease, negative stress test or CTCA results suggested no need for ICA. In patients with an intermediate (20% to 80%) pretest probability, a positive CTCA result suggested need to proceed with ICA (posttest probability, 93% [95% CI, 92% to 93%]) and a negative result suggested no need for further testing (posttest probability, 1% [CI, 1% to 1%]). Physicians could proceed directly with ICA in patients with a high (>80%) pretest probability (91% [CI, 90% to 92%]). LIMITATIONS Referral and verification bias might have influenced findings. Stress testing provides functional information that may add value to that from anatomical (CTCA or ICA) imaging. CONCLUSION Computed tomography coronary angiography seems most valuable in patients with intermediate pretest probability of disease, because the test can distinguish which of these patients need invasive angiography. These findings need to be confirmed before CTCA can be routinely recommended for these patients.
Independent Set Reconfiguration in Cographs and their Generalizations

We study the following independent set reconfiguration problem, called TAR‐Reachability: given two independent sets I and J of a graph G, both of size at least k, is it possible to transform I into J by adding and removing vertices one‐by‐one, while maintaining an independent set of size at least k throughout? This problem is known to be PSPACE‐hard in general. For the case that G is a cograph on n vertices, we show that it can be solved in time O(n2) , and that the length of a shortest reconfiguration sequence from I to J is bounded by 4n−2k (if it exists). More generally, we show that if G is a graph class for which (i) TAR‐Reachability can be solved efficiently, (ii) maximum independent sets can be computed efficiently, and which satisfies a certain additional property, then the problem can be solved efficiently for any graph that can be obtained from a collection of graphs in G using disjoint union and complete join operations. Chordal graphs and claw‐free graphs are given as examples of such a class G .
Screening for psychosocial distress amongst war-affected children: cross-cultural construct validity of the CPDS.

BACKGROUND Large-scale psychosocial interventions in complex emergencies call for a screening procedure to identify individuals at risk. To date there are no screening instruments that are developed within low- and middle-income countries and validated for that purpose. The present study assesses the cross-cultural validity of the brief, multi-informant and multi-indicator Child Psychosocial Distress Screener (CPDS). METHODS The CPDS data of total samples in targeted catchment areas of a psychosocial care program in four conflict-affected countries (Burundi n = 4193; Sri Lanka n = 2573; Indonesia n = 1624; Sudan n = 1629) were studied to examine the cross-cultural construct validity of the CPDS across settings. First, confirmatory factor analyses were done to determine the likelihood of pre-determined theory-based factor structures in each country sample. Second, multi-sample confirmatory factor analyses were done within each country sample to test measurement equivalence of the factor structure as a measure of construct validity. RESULTS A 3-factor structure reflecting the theoretical premises of the instrument (e.g., child distress, child resilience and contextual factors) was found in the samples from Burundi, Sri Lanka and Indonesia, albeit with context specific deviations. The robustness of the 3-factor structure as an indicator of construct validity was confirmed within these three samples by means of multi-sample confirmatory factor-analyses. A 3-factor structure was not found in the Sudan sample. CONCLUSIONS This study demonstrates the comparability of the assessment by the CPDS of the construct 'non-specific psychosocial distress' across three out of four countries. Robustness of the factor structure of the CPDS within different samples refers to the construct validity of the instrument. However, owing to context-specific deviations of inter-item relationships, the CPDS scores cannot be compared cross-culturally, a finding that confirms the need for attention to contextual factors when screening for non-specific psychosocial distress.
Glutathione Peroxidase 7 Suppresses Bile Salt-Induced Expression of Pro-Inflammatory Cytokines in Barrett's Carcinogenesis

Esophageal adenocarcinoma (EAC) is the most frequent malignancy in the esophagus in the US and its incidence has been rising rapidly in the past few decades. Chronic gastroesophageal reflux disease (GERD), where the esophageal epithelium is abnormally exposed to acid and bile salts, is a pro-inflammatory condition that is the main risk factor for the development of Barrett's esophagus (BE) and its progression to EAC. Glutathione peroxidase 7 (GPX7) is frequently silenced through DNA hypermethylation during Barrett's tumorigenesis. In this study, we investigated the role of GPX7 in regulating the bile salts-induced inflammatory signaling in Barrett's carcinogenesis. Using quantitative real-time PCR (qRT-PCR), we demonstrated a significant induction in the expression levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8) and chemokines (CXCL-1 and CXCL-2) in esophageal cells after exposure to acidic (pH4) or neutral (pH7) bile salts. Western blot analysis showed that exposure to acidic and neutral bile salts increased p-NF-κB-p65 (S536) protein levels independent of ROS. Reconstitution of GPX7 expression in EAC cells abolished the increase of p-p65 (S536) protein levels and mRNA expression of cytokines and chemokines upon treatment with acidic and neutral bile salts. Examination of human primary EAC tissues by qRT-PCR demonstrated significant overexpression of cytokines (TNF-α, IL-1β and IL-8) in EAC samples, as compared to normal samples, with significant inverse correlation with GPX7 expression level. Taken together, the loss of GPX7 expression promotes bile salt-induced activation of pro-inflammatory cytokines and chemokines; important contributors to GERD-associated Barrett's carcinogenesis.
Bitstream encryption and authentication with AES-GCM in dynamically reconfigurable systems

A high-speed and secure dynamic partial reconfiguration (DPR) system is realized with AES-GCM that guarantees both confidentiality and authenticity of FPGA bitstreams. In DPR systems, bitstream authentication is essential for avoiding fatal damage caused by unintended bitstreams. An encryption-only system can prevent bitstream cloning and reverse engineering, but cannot prevent erroneous or malicious bitstreams from being configured. Authenticated encryption is a relatively new concept that provides both message encryption and authentication, and AES-GCM is one of the latest authenticated encryption algorithms suitable for hardware implementation. We implemented the AES-GCM-based DPR system targeting the Virtex-5 device on an off-the-shelf board, and evaluated its throughput and hardware resource utilization. For comparison, we also implemented AES-CBC and SHA-256 modules on the same device. The experimental results showed that the AES-GCM-based system achieved higher throughput with less resource utilization than the AES/SHA-based system. The AES-GCM-module achieved more than 1 Gbps throughput and the entire system achieved about 800 Mbps throughput with reasonable resource utilization. This paper clarifies the advantage of using AES-GCM for protecting DPR systems.
Binary decision diagrams: a mathematical model for the path-related objective functions

This paper describes a mathematical model for all path length parameters (APL: Average Path Length, LPL: Longest Path Length, and SPL: Shortest Path Length) of Binary Decision Diagrams (BDDs). The proposed model is based on an empirical analysis of randomly generated Boolean functions. The formal core of the developed model is a unique equation for the path-related objective functions over the set of BDDs derived from Boolean functions with given number of variables and Sum of Products (SOP) terms. Simulation results show good correlation between the theoretical results and those predicted by the mathematical model. This model provides an estimation of the performance of a circuit prior to its final implementation, and can be applied to Boolean functions with any number of variables, any number of product terms, and any variable ordering method.
Bone density in post‐pubertal adolescent survivors of childhood brain tumors

Childhood cancer survivors are at high risk for reduced bone mineral density (BMD). Our objective was to determine whether post‐pubertal adolescent survivors of brain tumors, whose tumor or treatments placed them at risk for pituitary hormone deficiencies, have low BMD near time of peak bone mass accrual, and to assess risk factors for decreased BMD.
Multiple roles of nitric oxide in the airways

Nitric oxide is endogenously released in the airways by nitric oxide synthase. Functionally, two isoforms of this enzyme exist: constitutive and inducible. The former seems to protect airways from excessive bronchoconstriction while the latter has a modulatory role in inflammatory disorders of the airways such as asthma. This review explores the physiological and pathophysiological role of endogenous nitric oxide in the airways, and the clinical aspects of monitoring nitric oxide in exhaled air of patients with respiratory disease.
Development of a “steerable drill” for ACL reconstruction to create the arbitrary trajectory of a bone tunnel

It is often difficult for orthopedic surgeons to avoid LCL injury during ACL reconstruction. In this paper, we developed a steerable drill for ACL reconstruction to avoid LCL injury in the process of making a bone tunnel. There are two special requirements for the steerable drill mechanism. One is having sufficient flexibility to bend and avoid LCL while cutting the bone. The other is rigidity to avoid the buckle at the base of the drill when external force is exerted on the drill tip. These two requirements cannot be met simultaneously by using the previous material with uniform stiffness throughout its length. We therefore adopted a spring sheath with stiffness that varied between the top and base of the drill. This spring sheath has high stiffness at the base and low stiffness at the top. We performed the experiment to evaluate the effectiveness of the drill with uniform and non-uniform stiffness by comparing each result. Consequently, it was confirmed that the drill with non-uniform stiffness achieved 6 times the bending deformation and with 30% lower force as preventing the buckling compared to the drill with uniform stiffness. Subsequently, we presented a discussion concerning the reason for the experimental result, based on a physical long column model which simulated the steerable drill. In addition, at the end of this paper, a newly-developed control method to make the arbitrary trajectory of the bone tunnel using a steerable drill with non-uniform stiffness was described.
Revisiting Endosulfan

Endosulfan toxicity could precipitate gargantuan jeopardy and may result in irreversible and fatal damage. The spectrum of involvement may range from mild nausea, vomiting, and anxiety to intractable seizures and multiorgan damage resulting in death. We report a case of endosulfan poisoning complicated by multi-organ dysfunction, cardiac arrest, and death.
SWATH‐MS as a tool for biomarker discovery: From basic research to clinical applications

In the era of quantitative proteomics, where mass spectrometry plays a pivotal role, in particular associated with the use of data‐independent acquisition, it is time to perform an overview of this growing field with special focus on one of the most promising approaches: SWATH‐MS, and to present future perspectives for its application as a translational tool. Therefore, a summary of this technique is presented focusing on two key relevant concepts associated with its application in biomarker discovery: the protein library and the individual digital maps concepts. It is also the purpose of this review to document the likely impact of SWATH‐MS in both fundamental and translational research including biomarker identification and creation of diagnostic tools. To that end, the two concepts referred above were integrated with ongoing technical developments. Finally, some of the current restrictions for the implementation of SWATH‐MS on a large scale are identified, and potential solutions presented, namely protocol standardization combined with the use of the proper standards.
Puerarin protects brain tissue against cerebral ischemia/reperfusion injury by inhibiting the inflammatory response

Puerarin, a traditional Chinese medicine, exerts a powerful neuroprotective effect in cerebral ischemia/reperfusion injury, but its mechanism is unknown. Here, we established rat models of middle cerebral artery ischemia/reperfusion injury using the suture method. Puerarin (100 mg/kg) was administered intraperitoneally 30 minutes before middle cerebral artery occlusion and 8 hours after reperfusion. Twenty-four hours after reperfusion, we found that puerarin significantly improved neurological deficit, reduced infarct size and brain water content, and notably diminished the expression of Toll-like receptor-4, myeloid differentiation factor 88, nuclear factor kappa B and tumor necrosis factor-α in the ischemic region. These data indicate that puerarin exerts an anti-inflammatory protective effect on brain tissue with ischemia/reperfusion damage by downregulating the expression of multiple inflammatory factors.