Miracle-dz/UniFAR-FTUs huggingface dataset:
Reductions in acute medication use and healthcare resource utilization in patients with chronic migraine: a secondary analysis of a phase 3, randomized, double-blind, placebo-controlled study of galcanezumab with open-label extension (REGAIN)

Abstract Aims To analyze secondary objectives of the REGAIN study related to acute headache medication use and healthcare resource utilization (HCRU) in patients with chronic migraine treated with galcanezumab, a monoclonal antibody to calcitonin gene-related peptide. Methods Adults with chronic migraine (N = 1,113) were randomized (2:1:1) and treated with double-blind monthly injections of placebo, galcanezumab-120 mg, or galcanenzumab-240 mg for 3 months, followed by a 9-month open-label extension with 120 or 240 mg/month galcanezumab. Headache and medication information was collected by daily eDiary. HCRU was reported for the 6 months before randomization, monthly thereafter, and converted to rate per 100-patient-years. Results At baseline, 63–64% of patients met criteria for acute headache medication overuse. At Month 3, incidence of headache medication overuse in the galcanezumab groups (33% and 33%) was significantly lower than in the placebo group (46%, both p < .001) and was 16% and 23% in the previous-galcanezumab groups at Month 12. From a baseline of 14.5 to 15.5, reduction in mean number of monthly migraine headache days with acute headache medication use was also significantly greater in the galcanezumab groups at Month 3 (−4.2 and −4.9) than in placebo (−2.6, both p < .001), with reductions of −6.8 and −7.6 in the previous-galcanezumab groups at Month 12. Migraine-specific HCRU rates decreased for all groups, with no significant between-group differences at Month 3. At Month 12, in the two previous-galcanezumab groups, emergency room visits decreased by 58% and 75%, hospital admissions by 100%, and healthcare professional visits by 54% and 67%. Limitations Only 3 months of double-blind, placebo-controlled data, a longer HCRU recall period for baseline than postbaseline, and patients receiving care in the clinical trial itself, may limit generalizability. Conclusions Treatment with galcanezumab resulted in significant reductions in headache medication overuse and migraine headache days requiring acute medication use, with notable reductions in migraine-specific HCRU.
Molecule Sequence Generation with Rebalanced Variational Autoencoder Loss

Molecule generation is the procedure to generate initial novel molecule proposals for molecule design. Molecules are first projected into continuous vectors in chemical latent space, and then, these embedding vectors are decoded into molecules under the variational autoencoder (VAE) framework. The continuous latent space of VAE can be utilized to generate novel molecules with desired chemical properties and further optimize the desired chemical properties of molecules. However, there is a posterior collapse problem with the conventional recurrent neural network-based VAEs for the molecule sequence generation, which deteriorates the generation performance. We investigate the posterior collapse problem and find that the underestimated reconstruction loss is the main factor in the posterior collapse problem in molecule sequence generation. To support our conclusion, we present both analytical and experimental evidence. What is more, we propose an efficient and effective solution to fix the problem and prevent posterior collapse. As a result, our method achieves competitive reconstruction accuracy and validity score on the benchmark data sets.
First molecular detection of Neospora caninum from naturally infected slaughtered camels in Tunisia

Abstract Background Neospora caninum has been documented to infect most domestic wildlife but is known to primarily infect dogs and cattle and is considered an important cause of abortion in camels. Objective The aim of this study was to estimate the molecular detection of Neospora caninum in tissues of naturally infected camelids. Methods Brain, tongue (bottom and tip) and masseter muscles from 35 slaughtered camelids from Tataouine and Médenine regions were collected (n = 140 samples). PCR was used to amplify and detect N. caninum DNA in tissues samples followed by sequencing of some PCR products. A phylogenetic tree was then constructed to compare the partial sequences of the ITS1 gene with GenBank sequences. Histopathology examination was used to detect Neospora spp. cysts, but no lesions were observed. Results The overall molecular detection of N. caninum in camelids was 34.3% (12/35). The highest molecular detection of N. caninum was recorded in animals of more than 3 years old (6/9) and in animals aged between 1 and 3 years old (4/12). Whilst, the lowest molecular detection (2/14) was observed in animals 1 year or younger (p = 0.035). There were no significant differences in molecular detection of N. caninum according to both locality and gender (p > 0.05). Similarly, there was no difference of prevalence between different anatomical locations. Comparison of the partial sequences of the ITS1 gene revealed 100–95.5% similarity among our N. caninum amplicon (MW551566) and those deposited in GenBank. Conclusion These results highlight the presence of a risk infection by N. caninum in camels. For preventing N. caninum infection further studies are needed to improve our knowledge about the epidemiology of neosporosis in North Africa.
rTMS of the superior parietal lobule improves contrast discrimination but has no effect on the perception of distance between stimuli in the image plane

The superior parietal lobule (SPL) is a region of the brain that has been associated with a diverse range of high-level visual and cognitive functions. This suggested the possibility that it supports a lower-level function that is engaged by a wide range of experimental tasks. Analysis of tasks used in previous studies suggests that one such lower-level function might be the perception of the distance between stimuli in the image plane. In this study, we applied online high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left SPL or the vertex in order to further investigate the role played by this region in the perceived visual separation between points. As a control task, we asked participants to detect the difference in contrast between two Gabor patches. The results failed to support the main hypothesis, but we unexpectedly found that rTMS to left SPL improved peripheral contrast discrimination. Previous studies have found that rTMS to the right frontal eye field, which has strong functional connectivity with the SPL, has the same effect, suggesting the two areas work together to influence early visual areas.
Association between popliteal artery wall thickness and structural progression in patients with symptomatic knee osteoarthritis

Abstract Objective There is increasing evidence for the involvement of vascular disease in the pathogenesis of knee OA. Popliteal artery wall thickness can be used as a surrogate marker of atherosclerosis. We examined the association between popliteal artery wall thickness and knee cartilage volume in individuals with symptomatic knee OA. Methods This prospective cohort study analysed 176 participants from a randomized placebo-controlled trial examining the effect of atorvastatin on structural progression in knee OA. The participants underwent MRI of the study knee at baseline and 2-year follow-up. Popliteal artery wall thickness and tibial cartilage volume were measured from MRI using validated methods. The top quartile of the rate of tibial cartilage volume loss was defined as rapid progression. Results At baseline, every 10% increase in popliteal artery wall thickness was associated with 120.8 mm3 (95% CI 5.4, 236.2, P = 0.04) lower of medial tibial cartilage volume and 151.9 mm3 (95% CI 12.1, 291.7, P = 0.03) lower of lateral tibial cartilage volume. Longitudinally, for every 10% increase in popliteal artery wall thickness, the annual rate of medial tibial cartilage volume loss was increased by 1.14% (95% CI 0.09%, 2.20%, P = 0.03), and there was a 2.28-fold (95% CI 1.07, 4.83, P = 0.03) risk of rapid progression of medial tibial cartilage loss, adjusted for age, sex, BMI, tibial bone area, smoking, vigorous physical activity, and intervention group allocation. Conclusion The findings support a role for vascular pathology in the progression of knee OA. Targeting atherosclerosis has the potential to improve outcomes in knee OA.
Talking with strangers is surprisingly informative

Significance Conversation can be a useful source of learning about practically any topic. Information exchanged through conversation is central to culture and society, as talking with others communicates norms, creates shared understanding, conveys morality, shares knowledge, provides different perspectives, and more. Yet we find that people systematically undervalue what they might learn in conversation, anticipating that they will learn less than they actually do. This miscalibration stems from the inherent uncertainty of conversations, where it can be difficult to even conceive of what one might learn before one learns it. Holding miscalibrated expectations about the information value of conversation may discourage people from engaging in them more often, creating a potentially misplaced barrier to learning more from others.
Seasonal variations of nonmotor symptoms in patients with Parkinson's disease in Southeast China

Abstract Background: Studies suggest seasonal fluctuations of symptoms in Parkinson's disease (PD) patients in Western countries. However, the association between seasonal change and variation in nonmotor symptoms (NMS) in Chinese PD patients is unclear. Here, we studied whether there is a change rule with annual cycle with severity of NMS for patients with PD in Southeast China. Methods: We studied 1005 PD patients between April 2008 and October 2020. Patients were classified into four seasons according to the 24 Chinese solar terms, based on assessment date. We compared comprehensive NMS scales and polysomnography parameters among groups and conducted further analysis of disease severity. Results: Among the 1005 patients studied, the mean age was 64.2 ± 9.7 years and 569 (56.6%) of them were men. Relative to the summer group, patients assessed during winter had higher Scales for Outcomes in Parkinson's disease-Autonomic Dysfunction (SCOPA-AUT) scores (P = 0.045). The sleep efficiency factor scores of Pittsburgh Sleep Quality Index in patients were higher during spring than summer (P = 0.009). Among patients who completed polysomnography during the same period (n = 135), compared with summer follow-ups, we observed a higher percentage of NREMS1 in winter and spring follow-ups (P = 0.042, P = 0.011), a higher NREMS1 time in spring follow-ups (P = 0.0024), a lower NREMS2 time in winter follow-ups (P = 0.007), and a higher percentage of phasic rapid eye movement (REM)-sleep without atonia in autumn and winter follow-ups (P = 0.026 and P = 0.020, respectively). In a subset of patients with PD and REM sleep behavior disorder (RBD; n = 182), those visited during winter had higher scores for RBD questionnaire-Hong Kong and its factor 1 (dream-related sub-score) than those visited during summer (P = 0.034, P = 0.020). We observed similar findings for SCOPA-AUT and sleep efficiency factor scores in early stage patients in subgroup analysis. Conclusions: PD patients assessed for follow-up during summer showed less severe symptoms of autonomic dysfunction and RBD symptoms than those assessed in winter, and less sleep disturbance than those in spring and winter, suggesting that seasonal change and NMS fluctuation are related, especially in patients with early stage PD.
A Comparison Between Clinical Guidelines and Real-World Treatment Data in Examining the Use of Session Summaries: Retrospective Study

Background Although behavioral interventions have been found to be efficacious and effective in randomized clinical trials for most mental illnesses, the quality and efficacy of mental health care delivery remains inadequate in real-world settings, partly owing to suboptimal treatment fidelity. This “therapist drift” is an ongoing issue that ultimately reduces the effectiveness of treatments; however, until recently, there have been limited opportunities to assess adherence beyond large randomized controlled trials. Objective This study explored therapists’ use of a standard component that is pertinent across most behavioral treatments—prompting clients to summarize their treatment session as a means for consolidating and augmenting their understanding of the session and the treatment plan. Methods The data set for this study comprised 17,607 behavioral treatment sessions administered by 322 therapists to 3519 patients in 37 behavioral health care programs across the United States. Sessions were captured by a therapy-specific artificial intelligence (AI) platform, and an automatic speech recognition system transcribed the treatment meeting and separated the data to the therapist and client utterances. A search for possible session summary prompts was then conducted, with 2 psychologists validating the text that emerged. Results We found that despite clinical recommendations, only 54 (0.30%) sessions included a summary. Exploratory analyses indicated that session summaries mostly addressed relationships (n=27), work (n=20), change (n=6), and alcohol (n=5). Sessions with meeting summaries were also characterized by greater therapist interventions and included greater use of validation, complex reflections, and proactive problem-solving techniques. Conclusions To the best of our knowledge, this is the first study to assess a large, diverse data set of real-world treatment practices. Our findings provide evidence that fidelity with the core components of empirically designed psychological interventions is a challenge in real-world settings. The results of this study can inform the development of machine learning and AI algorithms and offer nuanced, timely feedback to providers, thereby improving the delivery of evidence-based practices and quality of mental health care services and facilitating better clinical outcomes in real-world settings.
XAF1 Protects Host against Emerging RNA Viruses by Stabilizing IRF1-Dependent Antiviral Immunity

Rapid and robust induction of antiviral genes is essential for the host to clear the invaded viruses. In addition to the IRF3/7-IFN-I-STAT1 signaling axis, the XAF1-IRF1 positive feedback loop synergistically or independently drives the transcription of antiviral genes. ABSTRACT XIAP-associated factor 1 (XAF1) is an interferon (IFN)-stimulated gene (ISG) that enhances IFN-induced apoptosis. However, it is unexplored whether XAF1 is essential for the host fighting against invaded viruses. Here, we find that XAF1 is significantly upregulated in the host cells infected with emerging RNA viruses, including influenza, Zika virus (ZIKV), and SARS-CoV-2. IFN regulatory factor 1 (IRF1), a key transcription factor in immune cells, determines the induction of XAF1 during antiviral immunity. Ectopic expression of XAF1 protects host cells against various RNA viruses independent of apoptosis. Knockout of XAF1 attenuates host antiviral innate immunity in vitro and in vivo, which leads to more severe lung injuries and higher mortality in the influenza infection mouse model. XAF1 stabilizes IRF1 protein by antagonizing the CHIP-mediated degradation of IRF1, thus inducing more antiviral IRF1 target genes, including DDX58, DDX60, MX1, and OAS2. Our study has described a protective role of XAF1 in the host antiviral innate immunity against RNA viruses. We have also elucidated the molecular mechanism that IRF1 and XAF1 form a positive feedback loop to induce rapid and robust antiviral immunity. IMPORTANCE Rapid and robust induction of antiviral genes is essential for the host to clear the invaded viruses. In addition to the IRF3/7-IFN-I-STAT1 signaling axis, the XAF1-IRF1 positive feedback loop synergistically or independently drives the transcription of antiviral genes. Moreover, XAF1 is a sensitive and reliable gene that positively correlates with the viral infection, suggesting that XAF1 is a potential diagnostic marker for viral infectious diseases. In addition to the antitumor role, our study has shown that XAF1 is essential for antiviral immunity. XAF1 is not only a proapoptotic ISG, but it also stabilizes the master transcription factor IRF1 to induce antiviral genes. IRF1 directly binds to the IRF-Es of its target gene promoters and drives their transcriptions, which suggests a unique role of the XAF1-IRF1 loop in antiviral innate immunity, particularly in the host defect of IFN-I signaling such as invertebrates.
An integrated lean methodology for improving patient flow in an emergency department – case study of a Saudi Arabian hospital

Abstract This study presents an integrated lean methodology for improving patient flow by identifying root causes of patient flow problems and proposing a lean patient flow process in emergency departments (EDs). The methodology combines the ‘voice of process’, the ‘voice of customers’ and the ‘voice of staff’ to identify non-value-added activities in the ED process. This integration was used to model, evaluate and improve work and process flow in the hospital’s ED. The current activities were analysed using process mapping and the A3 problem-solving sheet as visual tools to identify sources of waste. Aseer Central Hospital in Saudi Arabia was selected as the organisational case for this research. The study identified several critical areas of waste that significantly affect patient flow in the ED. The investigation reveals that these wastes were mainly related to the quality management, ED facilities, patients, physicians, nurses, administration, data/information and uncertainty/changes to work schedules in treatment. Based on the identified wastes, recommendations are made to design a lean process flow by eliminating root causes of overcrowding and waste in EDs. The proposed process model links key areas associated with the root causes of patient flow problem and highlighting critical areas that need improvement.
Caveolin‐1 influences mitochondrial plasticity and function in hepatic stellate cell activation

Caveolin‐1 (Cav‐1) is an integral membrane protein present in all organelles, responsible for regulating and integrating multiple signals as a platform. Mitochondria are extremely adaptable to external cues in chronic liver diseases, and expression of Cav‐1 may affect mitochondrial flexibility in hepatic stellate cells (HSCs) activation. We previously demonstrated that exogenous expression of Cav‐1 was sufficient to increase some classical markers of activation in HSCs. Here, we aimed to evaluate the influence of exogenous expression and knockdown of Cav‐1 on regulating the mitochondrial plasticity, metabolism, endoplasmic reticulum (ER)‐mitochondria distance, and lysosomal activity in HSCs. To characterize the mitochondrial, lysosomal morphology, and ER‐mitochondria distance, we perform transmission electron microscope analysis. We accessed mitochondria and lysosomal networks and functions through a confocal microscope and flow cytometry. The expression of mitochondrial machinery fusion/fission genes was examined by real‐time polymerase chain reaction. Total and mitochondrial cholesterol content was measured using Amplex Red. To define energy metabolism, we used the Oroboros system in the cells. We report that GRX cells with exogenous expression or knockdown of Cav‐1 changed mitochondrial morphometric parameters, OXPHOS metabolism, ER‐mitochondria distance, lysosomal activity, and may change the activation state of HSC. This study highlights that Cav‐1 may modulate mitochondrial function and structural reorganization in HSC activation, being a potential candidate marker for chronic liver diseases and a molecular target for therapeutic intervention.
The EICAT+ framework enables classification of positive impacts of alien taxa on native biodiversity

Species introduced through human-related activities beyond their native range, termed alien species, have various impacts worldwide. The IUCN Environmental Impact Classification for Alien Taxa (EICAT) is a global standard to assess negative impacts of alien species on native biodiversity. Alien species can also positively affect biodiversity (for instance, through food and habitat provisioning or dispersal facilitation) but there is currently no standardized and evidence-based system to classify positive impacts. We fill this gap by proposing EICAT+, which uses 5 semiquantitative scenarios to categorize the magnitude of positive impacts, and describes underlying mechanisms. EICAT+ can be applied to all alien taxa at different spatial and organizational scales. The application of EICAT+ expands our understanding of the consequences of biological invasions and can inform conservation decisions.
Design of Integrated Full-Duplex Wireless Transceivers

Author(s): Ramakrishnan, Sameet | Advisor(s): Nikolic, Borivoje | Abstract: Demand for mobile data traffic is projected to exceed 30 exabytes per month in 2020, representing an over 100x increase since 2010. Prior generations of cellular deployments have serviced increased demand largely through use of more bandwidth - from 200KHz in GSM, to now 100MHz in CA-LTE. This method of scaling is closed, as low frequency spectrum has crowded and saturated. A proposed technique to enhance spectrum access in 5G deployments is agile full-duplex (FD) transceivers, which can transmit and receive at overlapped frequencies, or tune to arbitrarily spaced transmit/receive(TX/RX) frequency division duplexed (FDD) channels, to make use of available spectrum. The key problem in such a system is mitigating the interference the system's own transmitter creates for its receiver during simultaneous operation. Current implementations mitigate TX to RX interference at the antenna interface using off-chip, fixed-frequency duplexers, limiting a device's spectrum access to a handful of pre-defined, widely separated TX/RX band combinations. Accordingly, a universal mobile device tunable across global carrier band combinations does not exist. This work develops a transceiver architecture enabling simultaneous transmission and reception on a single single shared antenna, over a wide frequency tuning range, for FD/FDD systems. The architecture is enabled by an active TX replica which cancels interference at the RX input, a highly linear passive-mixer first receiver design based on class-AB transconductors which operates linearly in the presence of residual TX interference, and digital adaptation techniques which match the interference over time-varying operating conditions. Analysis is presented for the system's fundamental performance bounds in power and sensitivity, leading to noise mitigation techniques which minimize receiver degradation in the presence of the cancellation circuits. The analysis is validated by two chip prototypes, which demonstrate over $g$50dB cancellation of a +16dBm peak 20MHz TX signal, from 1GHz to 2GHz, up to an antenna VSWR of 5:1. This work demonstrates the potential for a fully integrated, frequency-tunable FD/FDD transceiver system, which could ultimately double existing mobile network capacity, and enable a universal duplexer-less radio.