Miracle-dz/UniFAR-FTUs huggingface dataset:
Social Aspect of Functioning Deteriorates More Than Individual Aspect in Patients with Remitted Bipolar Disorder.

INTRODUCTION Many studies have demonstrated that patients with bipolar disorder (BD) suffer from significant functional impairment, even during remission periods. This study aimed to assess the levels of overall functioning and specific areas of functioning in remitted patients with BD compared with those in healthy controls. METHODS Eighty completely remitted patients with BD and 80 healthy controls were included in the study. The Bipolar Disorder Functioning Questionnaire (BDFQ), Young Mania Rating Scale, and Beck Depression Inventory were used. RESULTS There were fewer married and employed cohorts in the BD group than in the control group. Compared with healthy controls, patients with BD exhibited a worse functioning in terms of intellectual and sexual functioning, feelings of stigmatization, social withdrawal, household relationships, relationships with friends, and participation in social activities. There was no difference between the groups in terms of emotional functioning, daily activities and hobbies, taking initiative and self-sufficiency, and occupation. The total BDFQ scores of patients were lower than those of healthy controls. A better functionality was observed in patients using only a mood stabilizer than in patients using three or more drugs. CONCLUSION Remarkably, remitted patients with BD tended to perform daily activities well when these activities were not in a social context. Stigma-oriented interpersonal approaches can be particularly beneficial for these patients.
The Benefits of Identity Integration across Life Domains

ABSTRACT A significant portion of Americans identify as lesbian, gay, or bisexual (LGB). Troubling then is the fact that many of these individuals lack federal protections, with two-thirds reporting that they experience discrimination. This creates a difficult disclosure dilemma for LGB individuals. On one hand, self-verification theory and the work of Dr. Gregory Herek indicate that there are psychological benefits to being open about one’s identity in the workplace and social situations. In contrast, disclosing may open these individuals up to discriminatory experiences. To analyze the benefits and consequences of disclosure decisions across life domains, we collected survey data from 184 LGB individuals working at least 30 hours per week in the United States of America. Regression analyses showed that life satisfaction was maximized when disclosure was high and concordant across life domains. In other words, LGB individuals experienced the highest levels of life satisfaction when they were able to be open about their identity in work and non-work situations (i.e., identity integration). Notably, the most negative outcomes (e.g., worsened life satisfaction) were observed when identity disconnects (e.g., high disclosure at work, low disclosure in non-work domains) or identity denial (i.e., low disclosure in both domains) were present, confirming seminal theories of disclosure decisions across life domains. Our findings indicate that we should strive to create disclosure-supportive environments in work and non-work domains, with supportive organizational policies and active allies playing a crucial role in this process.
MACE for Diagnosis of Dementia and MCI: Examining Cut-Offs and Predictive Values

The definition of test cut-offs is a critical determinant of many paired and unitary measures of diagnostic or screening test accuracy, such as sensitivity and specificity, positive and negative predictive values, and correct classification accuracy. Revision of test cut-offs from those defined in index studies is frowned upon as a potential source of bias, seemingly accepting any biases present in the index study, for example related to sample bias. Data from a large pragmatic test accuracy study examining the Mini-Addenbrooke’s Cognitive Examination (MACE) were interrogated to determine optimal test cut-offs for the diagnosis of dementia and mild cognitive impairment (MCI) using either the maximal Youden index or the maximal correct classification accuracy. Receiver operating characteristic (ROC) and precision recall (PR) curves for dementia and MCI were also plotted, and MACE predictive values across a range of disease prevalences were calculated. Optimal cut-offs were found to be a point lower than those defined in the index study. MACE had good metrics for the area under the ROC curve and for the effect size (Cohen’s d) for both dementia and MCI diagnosis, but PR curves suggested the superiority for MCI diagnosis. MACE had high negative predictive value at all prevalences, suggesting that a MACE test score above either cut-off excludes dementia and MCI in any setting.
Biosynthesis of Polyketides in Streptomyces

Polyketides are a large group of secondary metabolites that have notable variety in their structure and function. Polyketides exhibit a wide range of bioactivities such as antibacterial, antifungal, anticancer, antiviral, immune-suppressing, anti-cholesterol, and anti-inflammatory activity. Naturally, they are found in bacteria, fungi, plants, protists, insects, mollusks, and sponges. Streptomyces is a genus of Gram-positive bacteria that has a filamentous form like fungi. This genus is best known as one of the polyketides producers. Some examples of polyketides produced by Streptomyces are rapamycin, oleandomycin, actinorhodin, daunorubicin, and caprazamycin. Biosynthesis of polyketides involves a group of enzyme activities called polyketide synthases (PKSs). There are three types of PKSs (type I, type II, and type III) in Streptomyces responsible for producing polyketides. This paper focuses on the biosynthesis of polyketides in Streptomyces with three structurally-different types of PKSs.
The Past, Present, and Future of Virtual Reality in Pharmacy Education

Objective. To characterize how virtual reality (VR) has been and is being used in pharmacy education, and evaluate the projected utility of VR technology in pharmacy education in the future. Findings. Virtual reality technology has been used in pharmacy education for many years to provide engaging learning experiences. Although these learning experiences were not available in the three-dimensional digital environments provided by current VR, they demonstrated improvements in learning. Recent technological advancements have substantially increased the potential usefulness of VR for pharmacy education by providing immersive educational activities that mimic real world experiences to reinforce didactic and laboratory concepts. Virtual reality training that uses head-mounted displays is just beginning in pharmacy education, but more educational VR programs are becoming available. Further research will be necessary to fully understand the potential impact of VR on pharmacy education. Summary. Virtual reality technology can provide an immersive and interactive learning environment, overcoming many of the early challenges faced by instructors who used virtual activities for pharmacy education. With further technological and software development, VR has the potential to become an integral part of pharmacy education.
Salicylate 5-Hydroxylase: Intermediates in Aromatic Hydroxylation by a Rieske Monooxygenase.

Rieske oxygenases (ROs) catalyze a large range of oxidative chemistry. We have shown that cis-dihydrodiol-forming Rieske dioxygenases first react with their aromatic substrates via an active site nonheme Fe(III)-superoxide; electron transfer from the Rieske cluster then completes the product-forming reaction. Alternatively, two-electron-reduced Fe(III)-peroxo or hydroxo-Fe(V)-oxo activated oxygen intermediates are possible and may be utilized by other ROs to expand the catalytic range. Here, the reaction of a Rieske monooxygenase, salicylate 5-hydroxylase, that does not form a cis-dihydrodiol is examined. Single-turnover kinetic studies show fast binding of salicylate and O2. Transfer of the Rieske electron required to form the gentisate product occurs through bonds over ∼12 Å and must also be very fast. However, the observed rate constant for this reaction is much slower than expected and sensitive to substrate type. This suggests that initial reaction with salicylate occurs using the same Fe(III)-superoxo-level intermediate as Rieske dioxygenases and that this reaction limits the observed rate of electron transfer. A transient intermediate (λmax = 700 nm) with an electron paramagnetic resonance (EPR) at g = 4.3 is observed after the product is formed in the active site. The use of 17O2 ( I = 5/2) results in hyperfine broadening of the g = 4.3 signal, showing that gentisate binds to the mononuclear iron via its C5-OH in the intermediate. The chromophore and EPR signal allow study of product release in the catalytic cycle. Comparison of the kinetics of single- and multiple-turnover reactions shows that re-reduction of the metal centers accelerates product release ∼300-fold, providing insight into the regulatory mechanism of ROs.
Second-order induction in prediction problems

Significance How do people generate beliefs about economic, political, and social events? A natural formula for the predicted value of a variable is its weighted average value in the past, where past values are given a higher weight if they were observed in circumstances more similar to the current ones. Agents learn from the data the best way to assess the similarity of past cases to the present one. The basic formula and this learning process appeared both in statistics and in psychology and they thus make sense for modeling economic agents. We study this process and identify circumstances under which agents are likely to agree on predictions and conditions under which disagreement over predictions may be reasonably expected. Agents make predictions based on similar past cases, while also learning the relative importance of various attributes in judging similarity. We ask whether the resulting “empirically optimal similarity function” (EOSF) is unique and how easy it is to find it. We show that with many observations and few relevant variables, uniqueness holds. By contrast, when there are many variables relative to observations, nonuniqueness is the rule, and finding the EOSF is computationally hard. The results are interpreted as providing conditions under which rational agents who have access to the same observations are likely to converge on the same predictions and conditions under which they may entertain different probabilistic beliefs.
Designing and Testing Apps to Support Patients With Cancer: Looking to Behavioral Science to Lead the Way

Background Behavioral science has a long and strong tradition of rigorous experimental and applied methodologies, which have produced several influential and far-reaching theoretical frameworks and have guided countless inquiries of human behavior in various contexts. In cancer care, behavioral scientists have established a firm foundation of research focused on understanding the experience of cancer and using that understanding to design and implement theory- and evidenced-based interventions to help patients cope with the cancer experience. Given the rich behavioral research base in oncology, behavioral scientists are ideally positioned to lead the integration of evidence-based science on behavior and behavior change into the development of smartphone apps supporting patients with cancer. Smartphone apps are being disseminated to patients with cancer with claims of being able to help them negotiate areas of vulnerability in their cancer experience. However, the vast majority of these apps are developed without the rigor and expertise of behavioral scientists. Objective In this article, we have illustrated the importance of behavioral science leading the development and evaluation of apps to support patients with cancer by providing an illustrative scientific process that our team of behavioral scientists, patient stakeholders, medical oncologists, and software developers used to empirically design and evaluate 2 patient-focused apps: the Discussion of Cost App (DISCO App) and MyPatientPal. Methods Using a focused literature review and a descriptive roadmap of our team’s process for designing and evaluating patient-focused behavioral apps for patients with cancer, we have demonstrated how behavioral scientists are integral to the development of empirically sound apps to help support patients with cancer. Specifically, we have illustrated the process by which our multidisciplinary team combined the established user-centered design principles and behavioral science theory and scientific rigor to design and evaluate 2 patient-focused apps. Results On the basis of initial acceptability and feasibility testing among patients and providers, our team has demonstrated how critical behavioral science is for designing and evaluating app-based interventions for patients with cancer. Conclusions Behavioral science can and should be coupled with user-centered design principles to provide theoretical guidance and the rigor of the scientific method, thereby adding the much-needed and critical evidence for these types of app-based interventions for patients with cancer.
Feasibility of Ski Mountaineering for Patients Following a Total Knee Arthroplasty: A Descriptive Field Study

Background: Total knee arthroplasty (TKA) is socially relevant due to its high prevalence, high incidence and the affected population. A subpopulation of TKA patients exists that strives to be active and also return to sports after total joint replacement. In this context, a further group of TKA patients is interested in high-impact physical activities and want to proceed with such activities even after surgery. Focusing on winter sports, there is still a lack of evidence on whether ski mountaineering is feasible for this subgroup of patients. Therefore, this feasibility study examines the effects of moderate ski mountaineering on strength, balance, functional abilities and mental health in persons following a TKA. Methods: Eight patients (six males, two females; median age, 63 ± Interquartile range 9 years) with TKA were included in this study. The volunteers, who were pre-selected for a 7-day holiday in Sankt Johann (Tyrol, Austria), participated in five guided ski mountaineering tours. Statistical analyses of non-parametric longitudinal data were performed using analysis of variance. For gait parameters and the Feeling Scale, one-factor longitudinal models were used. Statistical significance was set at the level of p < 0.05. Results: A significant decrease in the S3-Check MFT stability index (p = 0.04), a significant increase in general well-being (p = 0.05), and a trend towards a decrease in general stress (p = 0.1) were detected, while all other parameters were unaffected. Conclusion: A 7-day recreational ski mountaineering holiday had no negative effects on ski-experienced patients with TKA and seemed to increase well-being. Further studies should focus on larger groups and use controlled designs. Additionally, long-term effects should be evaluated.
Querying highly similar sequences

In this paper, we present a solution to the extreme similarity sequencing problem. The extreme similarity sequencing problem consists of finding occurrences of a pattern p in a set S(0), S(1), , S(k), of sequences of equal length, where S(i), for all 1≤i≤k, differs from S(0) by a constant number of errors - around 10 in practice. We present an asymptotically fast O(n + occ logocc) time algorithm, as well as a practical O(nk/w) time algorithm for solving this problem, where n is the length of a sequence, occ is the number of candidate occurrences reported by our technique, w is the size of the machine word, and the total number of errors is bounded by k - the number of sequences.
Texture classification using statistical geometrical features

This paper presents a new texture feature set based on the statistics of geometrical attributes of connected regions in a stack of binary images obtained from a texture image. Systematic evaluation using all the Brodatz textures shows that the new set outperforms the well-known statistical gray level dependence matrix, the recently proposed statistical feature matrix, and Liu's features. <<ETX>>
Prospective Clinical and Molecular Evaluation of Potential Plasmodium ovale curtisi and wallikeri Relapses in a High-transmission Setting

Abstract Background Plasmodium ovale curtisi and wallikeri are perceived as relapsing malarial parasites. Contrary to Plasmodium vivax, direct evidence for this hypothesis is scarce. The aim of this prospective study was to characterize the reappearance patterns of ovale parasites. Methods P. ovale spp. infected patients were treated with artemether-lumefantrine and followed biweekly for up to 1 year for the detection of reappearing parasitemia. Molecular analysis of reappearing isolates was performed to identify homologous isolates by genotyping and to define cases of relapse following predefined criteria. Results At inclusion, 26 participants were positive for P. ovale curtisi and/or P. ovale wallikeri. The median duration of follow-up was 35 weeks. Reappearance of the same P. ovale species was observed in 46% of participants; 61% of P. ovale curtisi and 19% of P. ovale wallikeri infection-free intervals were estimated to end with reappearance by week 32. Based on the predefined criteria, 23% of participants were identified with 1 or 2 relapses, all induced by P. ovale curtisi. Conclusion These findings are in line with the currently accepted relapse theory inasmuch as the reappearance of P. ovale curtisi strains following initial blood clearance was conclusively demonstrated. Interestingly, no relapse of P. ovale wallikeri was observed.
Heterogeneity in refractory acute myeloid leukemia

Significance Acute myeloid leukemia (AML) is the name given to a diverse set of highly fatal blood cancers. The typical initial treatment is combination cytotoxic chemotherapy with at least two drugs: 7 days of cytarabine with 3 days of an anthracycline. As treatment at initial diagnosis is often given emergently, there is a great need for pretreatment markers capable of identifying patients for whom standard treatment is likely to be suboptimal. This work uses RNA-sequencing analysis of a diverse cohort of highly annotated AML patient samples to demonstrate heterogeneity among those patients not responding to standard chemotherapy, then uses this information both to develop a prognostic classifier for survival and to suggest potentially superior therapeutic approaches for those at highest risk. Successful clinical remission to therapy for acute myeloid leukemia (AML) is required for long-term survival to be achieved. Despite trends in improved survival due to better supportive care, up to 40% of patients will have refractory disease, which has a poorly understood biology and carries a dismal prognosis. The development of effective treatment strategies has been hindered by a general lack of knowledge about mechanisms of chemotherapy resistance. Here, through transcriptomic analysis of 154 cases of treatment-naive AML, three chemorefractory patient groups with distinct expression profiles are identified. A classifier, four key refractory gene signatures (RG4), trained based on the expression profile of the highest risk refractory patients, validated in an independent cohort (n = 131), was prognostic for overall survival (OS) and refined an established 17-gene stemness score. Refractory subpopulations have differential expression in pathways involved in cell cycle, transcription, translation, metabolism, and/or stem cell properties. Ex vivo drug sensitivity to 122 small-molecule inhibitors revealed effective group-specific targeting of pathways among these three refractory groups. Gene expression profiling by RNA sequencing had a suboptimal ability to correctly predict those individuals resistant to conventional cytotoxic induction therapy, but could risk-stratify for OS and identify subjects most likely to have superior responses to a specific alternative therapy. Such personalized therapy may be studied prospectively in clinical trials.
Electrophysiological and pharmacological characterization of a novel and potent neuronal Kv7 channel opener SCR2682 for antiepilepsy

Voltage‐gated Kv7/KCNQ/M potassium channels play an essential role in the control of membrane potential and neuronal excitability. Activation of the neuronal Kv7/KCNQ/M‐current represents an attractive therapeutic strategy for treatment of hyperexcitability‐related neuropsychiatric disorders such as epilepsy, pain, and depression, which is an unmet medical need. In this study, we synthesized and characterized a novel compound, N‐(4‐(2‐bromo‐6,7‐dihydrothieno[3,2‐c]pyridin‐5(4H)‐yl)‐2,6‐dimethylphenyl)‐3,3‐dimethylbutanamide (SCR2682) 2,6‐dimethyl‐4‐(piperidin‐yl) phenyl)‐amide derivative, that exhibits selective and potent activation of neuronal Kv7/KCNQ/M‐channels. Whole‐cell patch‐clamp recordings of human embryonic kidney 293 cells expressing Kv7.2/Kv7.3 channels show that SCR2682 selectively activates the channel current in a dose‐dependent manner with an EC50 of 9.8 ± 0.4 nM, which is ∼100‐fold more potent than a U.S. Food and Drug Administration–approved antiepileptic drug (retigabine) for treatment of partial epilepsy. SCR2682 shifts voltage‐dependent activation of the Kv7.2/7.3 current toward more negative membrane potential, to about −37 mV (V1/2). SCR2682 also activates the native M‐current in rat hippocampal or cortical neurons, causing marked hyperpolarization and potent inhibition of neuronal firings. Mechanistically, mutating the tryptophan residue 236 located at the fifth transmembrane segment of Kv7.2 abolishes the chemical activation of the channel by SCR2682. Furthermore, intraperitoneal or intragastric administration of SCR2682 results in a dose‐dependent inhibition of seizures by maximal electroshock. Taken together, our findings demonstrate that a novel small molecule, SCR2682, selectively and potently activates neuronal Kv7 channels and reverses epileptic seizures in rodents. Thus, SCR2682 may warrant further evaluation for clinical development of antiepileptic therapy. —Zhang, F. , Liu, Y. , Tang, F. , Liang, B. , Chen, H. , Zhang, H. , Wang, K. Electrophysiological and pharmacological characterization of a novel and potent neuronal Kv7 channel opener SCR2682 for antiepilepsy. FASEB J. 33, 9154–9166 (2019). www.fasebj. org
Fault-Tolerant Middleware for Grid Computing

The major challenge in Grid environment is fault tolerance. Faults ranging from machine crashes, media failures, operator errors and random data corruption results in loss of data, both temporarily and permanently. The paper proposes a solution for handling faults in grid environment. Fault-Tolerance using Adaptive Replication in Grid Computing (FTARG) is an adaptive replication middleware which addresses the fault tolerance of Grid based applications by providing data replication at different sites. FTARG is an Aneka based Grid middleware especially designed for high-performance Grid based applications. FTARG enables data synchronization between multiple heterogeneous databases located in the Grid by supporting a variety of synchronization modes. Experimental analysis proves that proposed FTARG handles faults in the Grid by improving the performance of data management for large scale complex grid based applications.