Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I Assessment of Safety and Therapeutic Activity of BAY1436032 in Patients with IDH1-Mutant Solid Tumors

Purpose: BAY1436032, an inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1), was active against multiple IDH1-R132X solid tumors in preclinical models. This first-in-human study was designed to determine the safety and pharmacokinetics of BAY1436032, and to evaluate its potential pharmacodynamics and antitumor effects. Patients and Methods: The study comprised of dose escalation and dose expansion cohorts. BAY1436032 tablets were orally administered twice daily on a continuous basis in subjects with mIDH1 solid tumors. Results: In dose escalation, 29 subjects with various tumor types were administered BAY1436032 across five doses (150–1,500 mg twice daily). BAY1432032 exhibited a relatively short half-life. Most evaluable subjects experienced target inhibition as indicated by a median maximal reduction of plasma R-2-hydroxyglutarate levels of 76%. BAY1436032 was well tolerated and an MTD was not identified. A dose of 1,500 mg twice daily was selected for dose expansion, where 52 subjects were treated in cohorts representing four different tumor types [lower grade glioma (LGG), glioblastoma, intrahepatic cholangiocarcinoma, and a basket cohort of other tumor types]. The best clinical outcomes were in subjects with LGG (n = 35), with an objective response rate of 11% (one complete response and three partial responses) and stable disease in 43%. As of August 2020, four of these subjects were in treatment for >2 years and still ongoing. Objective responses were observed only in LGG. Conclusions: BAY1436032 was well tolerated and showed evidence of target inhibition and durable objective responses in a small subset of subjects with LGG.
Challenges and opportunities in translational pain research – An opinion paper of the working group on translational pain research of the European pain federation (EFIC)

For decades, basic research on the underlying mechanisms of nociception has held promise to translate into efficacious treatments for patients with pain. Despite great improvement in the understanding of pain physiology and pathophysiology, translation to novel, effective treatments for acute and chronic pain has however been limited, and they remain an unmet medical need. In this opinion paper bringing together pain researchers from very different disciplines, the opportunities and challenges of translational pain research are discussed. The many factors that may prevent the successful translation of bench observations into useful and effective clinical applications are reviewed, including interspecies differences, limited validity of currently available preclinical disease models of pain, and limitations of currently used methods to assess nociception and pain in non‐human and human models of pain. Many paths are explored to address these issues, including the backward translation of observations made in patients and human volunteers into new disease models that are more clinically relevant, improved generalization by taking into account age and sex differences, and the integration of psychobiology into translational pain research. Finally, it is argued that preclinical and clinical stages of developing new treatments for pain can be improved by better preclinical models of pathological pain conditions alongside revised methods to assess treatment‐induced effects on nociception in human and non‐human animals.
Optimized Diagnostic Approach to Patients Suspected of Superior Semicircular Canal Dehiscence

Objectives: Current methods of diagnosing superior semicircular canal dehiscence syndrome (SCDS) include a clinical exam, audiometric testing, temporal bone computer tomography (CT) imaging, and vestibular evoked myogenic potential (VEMP) testing. The main objective of this study was to develop an improved diagnostic approach to SCDS optimized for accuracy, efficiency, and safety that utilizes clinical presentation, audiometric testing, CT imaging, high-frequency cervical VEMP (cVEMP) testing, and patient treatment preference. A secondary aim was to investigate the cost associated with the current versus proposed diagnostic paradigms. Design: All patients who underwent cVEMP testing since introduction of the 2 kHz cVEMP in our clinical protocol in July 2018 were screened. Patients suspected of SCDS based upon symptoms who also had available audiogram, CT scan, and 2 kHz cVEMP were included (58 ears). Patients were categorized as dehiscent, thin, or not dehiscent based on their CT scan. Symptom prevalence and cVEMP outcomes were analyzed and compared for all groups. The accuracy of the 2 kHz cVEMP was calculated using CT imaging as the standard. Using a combination of patient symptomatology, audiometric, CT and 2 kHz cVEMP data, as well as patient preference, a best clinical practice approach was developed. The cost associated with this approach was calculated and compared with cost of the current SCDS diagnostic workup using Medicare reimbursement rates. Results: In the overall patient population suspected of SCDS based on clinical presentation, the sensitivity and specificity of 2 kHz cVEMP were 76% and 100%, respectively, while the positive and negative predictive values were 100% and 84.6%, assuming that the CT scan finding was correct. Autophony was the most common symptom in patients who had both superior semicircular canal dehiscence on CT imaging plus abnormal 2 kHz cVEMP (p < 0.001). Combining patient symptomatology, 2 kHz normalized peak to peak cVEMP amplitude, and patient treatment preference to determine, which patients should undergo CT scanning resulted in a potential cost reduction between 45% and 61%. Conclusion: In patients suspected of SCDS based on their clinical presentation, the combination of symptomatology, 2 kHz cVEMP data, and patient preference can be used to determine which patients should undergo CT scanning, resulting in a diagnostic cost reduction and reduced patient radiation exposure.
Acute moderate‐intensity aerobic exercise promotes purinergic and inflammatory responses in sedentary, overweight and physically active subjects

What is the central question of this study? How does moderate‐intensity aerobic exercise affect the behaviour of purinergic enzymes in sedentary, overweight and physically active subjects? What is the relationship between purinergic and inflammatory responses triggered by exercise? What is the main finding and its importance? Moderate‐intensity aerobic exercise modifies the activity of purinergic enzymes and the levels of nucleotides and nucleosides. These results are similar in subjects with different biological characteristics. 5′‐Nucleotidase activity and adenosine levels are associated with inflammatory responses. This study suggests that a purinergic pathway is related to the inflammatory responses triggered by exercise.
Core Concern: Structural imperialism and the impact of Sept. 11 on U.S. coverage of international news

A longitudinal study of international news in U.S. newspapers before and after Sept. 11, 2001 was used to examine whether the reaction of U.S. media to that day’s news events affected coverage in ways that would be predicted or explained by the theory of structural imperialism. This theory says news produced by and about core countries dominates news about the periphery. It therefore would predict a shift in the balance of news flow in response to Sept. 11, because an event with such significance to the United States and its interests around the world would tend to make coverage more “U.S. centric” and reporting on other countries would be marginalized or pushed out of the news flow. Statistical analysis of the number of news stories about more than 150 countries published in elite newspapers over a two-year period found support for the theorized view that Third World coverage was adversely affected after Sept. 11, which can be interpreted as evidence of structural imperialism having an impact on news flow. Disciplines Communication Comments Presentation at the 6th Annual Convention for Media Ecology Association, June 22–26, 2005, Fordham University, New York, New York. This conference proceeding is available at Fisher Digital Publications: http://fisherpub.sjfc. edu/commj_facpub/11 Structural imperialism and post-Sept. 11 news coverage– page 1
Identification of RNA pseudouridine sites using deep learning approaches

Pseudouridine(Ψ) is widely popular among various RNA modifications which have been confirmed to occur in rRNA, mRNA, tRNA, and nuclear/nucleolar RNA. Hence, identifying them has vital significance in academic research, drug development and gene therapies. Several laboratory techniques for Ψ identification have been introduced over the years. Although these techniques produce satisfactory results, they are costly, time-consuming and requires skilled experience. As the lengths of RNA sequences are getting longer day by day, an efficient method for identifying pseudouridine sites using computational approaches is very important. In this paper, we proposed a multi-channel convolution neural network using binary encoding. We employed k-fold cross-validation and grid search to tune the hyperparameters. We evaluated its performance in the independent datasets and found promising results. The results proved that our method can be used to identify pseudouridine sites for associated purposes. We have also implemented an easily accessible web server at http://103.99. 176.239/ipseumulticnn/.
Cardiovascular effectiveness of human-based vs. exendin-based glucagon like peptide-1 receptor agonists: a retrospective study in patients with type 2 diabetes.

AIMS Glucagon like peptide-1 (GLP-1) receptor agonists (GLP-1RA) are effective to control type 2 diabetes (T2Ds) and can protect from adverse cardiovascular outcomes. GLP-1RA are based on the human GLP-1 or the exendin-4 sequence. We compared cardiovascular outcomes of patients with T2D who received human-based or exendin-based GLP-1RA in routine clinical practice. METHODS AND RESULTS We performed a retrospective study on the administrative database of T2D patients from the Veneto Region (North-East Italy). We identified patients who initiated a human-based or exendin-based GLP-1RA from 2011 to 2018. The primary outcome was occurrence of major adverse cardiovascular events (MACE). Secondary outcomes were individual MACE components, revascularization, hospitalization for heart failure, or for cardiovascular causes. From 330 193 patients with diabetes, 6620 were new users of GLP-1RA. After propensity score matching, we analysed 1098 patients in each group, who were on average 61 years old, 59.5% males, 13% with established cardiovascular disease, had an estimated diabetes duration of 8.4 years, and a baseline HbA1c of 7.9%. During a median follow-up of 18 months, patients treated with human-based GLP-1RA as compared to those treated with exendin-based GLP-1RA, showed lower rates of MACE [hazard ratio 0.61; 95% confidence interval (CI) 0.39-0.95], myocardial infarction (0.51; 95% CI 0.28-0.94), and hospitalization for cardiovascular causes (0.66; 95% CI 0.47-0.92). CONCLUSION We observed better cardiovascular outcomes among patients treated with human-based vs. exendin-based GLP-1RA under routine care. In the absence of comparative trials and in view of the limitations of retrospective studies, this finding provides a moderate level of evidence to guide clinical decision.
Psychological and neuropsychological underpinnings of attention-deficit/hyperactivity disorder assessment

The identification and diagnosis of attention-deficit/hyperactivity disorder (ADHD) is extremely important in order to help change the trajectory of an individual’s life outcomes. A review of the current state of evidence-based assessment of ADHD is dominated by the DSM-5’s conceptualization of behaviorally-oriented diagnostic criteria. This assumption that the DSM-5’s method for identifying ADHD is the gold standard underlies the research base that evaluates the incremental validity of measures and methods for diagnosing it. That is, when evaluating whether a measure is useful in the identification of ADHD, the ‘right answer’ is based on the DSM-5’s behaviorally-oriented definition. An alternative model for considering the fact that ADHD is a neurodevelopmental disorder, with its roots in executive dysfunction, is proposed. Using neuropsychological and cognitive tests to identify executive functioning problems can be combined with rating scales and interviews to diagnose ADHD in a way that does not ascribe entirely to a behavioral definition of the disorder.
Selective decay of terrestrial organic carbon during transport from land to sea

Numerous studies have estimated carbon exchanges at the land–atmosphere interface, more recently also including estimates at the freshwater–atmosphere interface. Less attention has been paid to lateral carbon fluxes, in particular to the fate of terrestrial carbon during transport from soils via surface waters to the sea. Using extensive datasets on soil, lake and river mouth chemistry of the boreal/hemiboreal region we determined organic carbon (OC) stocks of the O horizon from catchment soils, annual OC transports through more than 700 lakes (OClakeflux) and the total annual OC transport at Sweden's 53 river mouths (OCseaflux). We show here that a minimum of 0.03–0.87% yr−1 of the OC soil stocks need to be exported to lakes in order to sustain the annual OClakeflux. Across Sweden we estimated a total OClakeflux of ~2.9 Mtonne yr−1, which corresponds to ~10% of Sweden's total terrestrial net ecosystem production, and it is over 50% higher than the total OCseaflux. The OC loss during transport to the sea follows a simple exponential decay with an OC half‐life of ~12 years. Water colour, a proxy often used for dissolved humic matter, is similarly lost exponentially but about twice as fast as OC. Thus, we found a selective loss of the coloured portion of soil‐derived OC during its transport through inland waters, prior to being discharged into the sea. The selective loss is water residence time dependent, resulting in that the faster the water flows through the landscape the less OC and colour is lost. We conclude that increases in runoff will result in less efficient losses of OC, and particularly of colour, if the time for OC transformations in the landscape shortens. Consequently, OC reaching the sea is likely to become more coloured, and less processed, which can have far‐reaching effects on biogeochemical cycles.
Electrochemical Investigation of Gold Uptake From Chloride Solution by Magnetite

An electrochemical method (potential sweep method) was utilized to investigate the nature of the absorbed gold on magnetite and to determine the gold sorption mechanism. A magnetite electrode was prepared in the laboratory, made in contact with a gold chloride solution at different conditions, and was subjected to cyclic voltammetry. The cyclic voltammogram of the magnetite electrode pretreated in a gold chloride solution recorded an anodic current peak at around 1.0 V (vs. Ag/AgCl), which corresponds to the current generated for the anodic dissolution of metallic gold in a chloride medium. The results of the electrochemical experiments suggest that gold chloride complexes are reduced to metallic gold on the surface of magnetite. A four-stage gold uptake mechanism was proposed: (i) the transport of from the bulk solution to the magnetite surface, (ii) adsorption of ions on magnetite surface by electrostatic attraction, (iii) electrochemical reduction of to metallic Au, and (iv) the transport of soluble species to the solution phase. The electrochemical investigation also revealed that Fe3+ ions released from magnetite into the solution, suppressed the gold uptake at the acidic pH region.
Anylasis of Nail Bed Injuries

Background Although fingertip and nail bed injuries have a high incidence, appropriate management of nail bed injuries remains controversial. This study is the completion of data derived from nail bed injuries with follow-up of a minimum of 6 months to suggest an appropriate treatment. Methods In the retrospective study, we analyzed data from 549 nail bed injuries for 6 years and age, type of injury, fractures, treatment methods, and outcomes were reviewed. Results were determined and these were divided to identical to the opposite group, abnormalities based on Zook criteria. Statistical analysis was done according to injury category (type, site, nail substitute, and fracture) and overall final grade. Results Over 50% (293 cases) had excellent results. Rates of very good, good, fair, and poor results were 22.6%, 11.3%, 6.2%, and 6.6%, respectively. Poorer results were obtained for fold injuries, crush, and avulsive injuries. The presence of a fracture was associated with poor results. Conclusions The cause of poor results is thought to be multifactorial. Although, overall outcomes were good, nail splitting, nail roughness, and nail adherence can cause dirtiness, catching, bending, and various cosmetic problems. Thus, careful suture and replacement of nail to nail fold are important to reach good results.
The effectiveness of cultural competence education in enhancing knowledge acquisition, performance, attitudes, and student satisfaction among undergraduate health science students: a scoping review

Purpose Cultural competence in healthcare assists in the delivery of culturally sensitive and high-quality services. This scoping review aims to provide an overview of the available evidence and to examine the effectiveness of classroom-based intervention strategies used to enhance the cultural competence of undergraduate health science students. Methods A comprehensive and systematic literature search was undertaken in databases, including Cochrane Library, Medline, and Emcare. Articles were eligible if they employed an experimental study design to assess classroom-based cultural competency education for university students across the health science disciplines. Two reviewers independently screened and extracted relevant data pertaining to study and participant characteristics using a charting table. The outcomes included knowledge, attitudes, skills, and perceived benefits. Results Ten studies were analysed. Diverse approaches to cultural education exist in terms of the mode, frequency, and duration of interventions. For the knowledge outcome, students who experienced cultural education interventions yielded higher post-test scores than their baseline cultural knowledge, but without a significant difference from the scores of students who did not receive interventions. Data relating to the skills domain demonstrated positive effects for students after experiencing interventions. Overall, students were satisfied with their experiences and demonstrated improvements in confidence and attitudes towards culturally competent practice. Conclusion Across health science disciplines, cultural competency interventions were shown to be effective in enhancing knowledge acquisition, performance of skills, attitudes, and student satisfaction. Future research is necessary to address the significant absence of control arms in the current literature, and to assess long-term effects and patient-related outcomes.
Parallel and Serial Sensory Processing in Developing Primary Somatosensory and Motor Cortex

It is generally supposed that primary motor cortex (M1) receives somatosensory input predominantly via primary somatosensory cortex (S1). However, a growing body of evidence indicates that M1 also receives direct sensory input from the thalamus, independent of S1; such direct input is particularly evident at early ages before M1 contributes to motor control. It is generally supposed that primary motor cortex (M1) receives somatosensory input predominantly via primary somatosensory cortex (S1). However, a growing body of evidence indicates that M1 also receives direct sensory input from the thalamus, independent of S1; such direct input is particularly evident at early ages before M1 contributes to motor control. Here, recording extracellularly from the forelimb regions of S1 and M1 in unanesthetized rats at postnatal day (P)8 and P12, we compared S1 and M1 responses to self-generated (i.e., reafferent) forelimb movements during active sleep and wake, and to other-generated (i.e., exafferent) forelimb movements. At both ages, reafferent responses were processed in parallel by S1 and M1; in contrast, exafferent responses were processed in parallel at P8 but serially, from S1 to M1, at P12. To further assess this developmental difference in processing, we compared exafferent responses to proprioceptive and tactile stimulation. At both P8 and P12, proprioceptive stimulation evoked parallel responses in S1 and M1, whereas tactile stimulation evoked parallel responses at P8 and serial responses at P12. Independent of the submodality of exafferent stimulation, pairs of S1-M1 units exhibited greater coactivation during active sleep than wake. These results indicate that S1 and M1 independently develop somatotopy before establishing the interactive relationship that typifies their functionality in adults. SIGNIFICANCE STATEMENT Learning any new motor task depends on the ability to use sensory information to update motor outflow. Thus, to understand motor learning, we must also understand how animals process sensory input. Primary somatosensory cortex (S1) and primary motor cortex (M1) are two interdependent structures that process sensory input throughout life. In adults, the functional relationship between S1 and M1 is well established; however, little is known about how S1 and M1 begin to transmit or process sensory information in early life. In this study, we investigate the early development of S1 and M1 as a sensory processing unit. Our findings provide new insights into the fundamental principles of sensory processing and the development of functional connectivity between these important sensorimotor structures.
Human Infection with Eurasian Avian-Like Swine Influenza A(H1N1) Virus, the Netherlands, September 2019

We report a zoonotic infection of a pig farmer in the Netherlands with a Eurasian avian-like swine influenza A(H1N1) virus that was also detected in the farmed pigs. Both viruses were antigenically and genetically characterized. Continued surveillance of swine influenza A viruses is needed for risk assessment in humans and swine.
Can Interactive Media Attenuate Psychological Reactance to Health Messages? A Study of the Role Played by User Commenting and Audience Metrics in Persuasion

ABSTRACT Health advocacy messages can generate psychological reactance and lead to message rejection. Could we offset this negative outcome by providing more agency and interactivity to message receivers? Are individuals more likely to be receptive if health campaigns provided them an opportunity to comment on the advocacy messages? Will they be more likely to follow the advocated behavior if a lot of other receivers have expressed approval of those messages, i.e., will they follow the bandwagon and show lesser reactance? We investigated these questions by conducting a 2 (bandwagon cue: strong vs. weak) X 2 (comment action: presence vs. absence) X 2 (message threat: high vs. low) between-subjects experiment (N = 179) with an online health message. Findings suggest that strong bandwagon cues can reduce reactance and improve persuasion by eliciting bandwagon perceptions. Comment action is associated with a strong sense of agency, which positively predicts intention to follow the message recommendation. Technological affordances interact with threat level of the message and with each other in influencing users’ evaluation and acceptance of persuasive health messages.