Miracle-dz/UniFAR-FTUs huggingface dataset:
Sudapyridine (WX-081), a Novel Compound against Mycobacterium tuberculosis

This study is aimed at chemotherapy for multidrug-resistant tuberculosis (MDR-TB), mainly to develop new anti-TB drugs to kill Mycobacterium tuberculosis, a microorganism with strong drug resistance. In this study, the structure of a potent antituberculosis compound, bedaquiline (BDQ), was optimized to generate a new compound, sudapyridine (WX-081). ABSTRACT Bedaquiline (BDQ) was historically listed by the World Health Organization (WHO) in 2018 as the preferred option for rifampin-resistant tuberculosis (RR-TB) and multidrug-resistant tuberculosis (MDR-TB). However, when there is no other effective regimen, the side effects and weaknesses of BDQ limit its use of MDR-TB. There is a black box warning in the package insert of BDQ to warn patients and health care professionals that this drug may increase the risk of unexplained mortality and QT prolongation, which may lead to abnormal and potentially fatal cardiac rhythm. In addition, the phenomenon of elevated liver enzymes in clinical trials of BDQ is a potential sign of hepatotoxicity. Therefore, it is still a medical need to develop new compounds with better safety profiles, patient compliance, affordability, and the ability to retain the efficacy of BDQ. After extensive lead generation and optimization, a new analog, sudapyridine (WX-081), was selected as a potential new antituberculosis candidate to move into clinical trials. Here, we evaluated WX-081's overall preclinical profile, including efficacy, pharmacokinetics, and toxicology. The in vitro activity of WX-081 against drug-sensitive and drug-resistant tuberculosis was comparable to that of BDQ, and there was comparable efficacy between WX-081 and BDQ in both acute and chronic mouse tuberculosis models using low-dose aerosol infection. Moreover, WX-081 improved pharmacokinetic parameters and, more importantly, had no adverse effects on blood pressure, heart rate, or qualitative ECG parameters from nonclinical toxicology studies. WX-081 is under investigation in a phase 2 study in patients. IMPORTANCE This study is aimed at chemotherapy for multidrug-resistant tuberculosis (MDR-TB), mainly to develop new anti-TB drugs to kill Mycobacterium tuberculosis, a microorganism with strong drug resistance. In this study, the structure of a potent antituberculosis compound, bedaquiline (BDQ), was optimized to generate a new compound, sudapyridine (WX-081). This experiment showed that its efficacy was similar to that of BDQ, its cardiotoxicity was lower, and it had good kinetic characteristics. This compound will certainly achieve significant results in the control and treatment of tuberculosis in the future.
Better than ‘normal’: Describing the distribution of and outliers in RBC usage

Optimizing a hospital blood inventory requires understanding the distribution of blood usage at the institution. Standard methods for describing red blood cell (RBC) usage like mean and standard deviation assume a normal distribution. Other distributions may fit the distribution of daily RBC usage better and provide more accurate insights into blood usage and in6ventory management.
Contrast‐Enhanced Fluid‐Attenuated Inversion Recovery in Neuroimaging: A Narrative Review on Clinical Applications and Technical Advances

While contrast‐enhanced fluid‐attenuated inversion recovery (FLAIR) has long been regarded as an adjunct sequence to evaluate leptomeningeal disease in addition to contrast‐enhanced T1‐weighted imaging, it is gradually being used for more diverse pathologies beyond leptomeningeal disease. Contrast‐enhanced FLAIR is known to be highly sensitive to low concentrations of gadolinium within the fluid. Accordingly, recent research has suggested the potential utility of contrast‐enhanced FLAIR in various kinds of disease, such as Meniere's disease, seizure, stroke, traumatic brain injury, and brain metastasis, in addition to being used for visualizing glymphatic dysfunction. However, its potential applications have been reported sporadically in an unorganized manner. Furthermore, the exact mechanism for its superior sensitivity to low concentrations of gadolinium has not been fully understood. Rapidly developing magnetic resonance technology and unoptimized parameters for FLAIR may challenge its accurate application in clinical practice. This review provides the fundamental mechanism of contrast‐enhanced FLAIR, systematically describes its current and potential clinical application, and elaborates on technical considerations for its optimization.
Robust Tightly-Coupled Visual-Inertial Odometry with Pre-built Maps in High Latency Situations

In this paper, we present a novel monocular visual-inertial odometry system with pre-built maps deployed on the remote server, which can robustly run in real-time on a mobile device even in high latency situations. By tightly coupling VIO with geometric priors from pre-built maps, our system can tolerate the high latency and low frequency of global localization service, which is especially suitable for practical applications when the localization service is deployed on the remote server. Firstly, sparse point clouds are obtained from the dense mesh by the ray casting method according to the localization results. The dense mesh can be reconstructed from the point clouds generated by Structure-from-Motion. We directly use the sparse point clouds in feature tracking and state update to suppress drift. In the process of feature tracking, the high local accuracy of VIO is fully utilized to effectively remove outliers and make our system robust. The experiments on EurocMav datasets and simulation datasets show that compared with state-of-the-art methods, our method can achieve better results in terms of both precision and robustness. The effectiveness of the proposed method is further demonstrated through a real-time AR demo on a mobile phone with the aid of visual localization on the remote server.
Learning-Based DoS Attack Power Allocation in Multiprocess Systems

We study the denial-of-service (DoS) attack power allocation optimization in a multiprocess cyber–physical system (CPS), where sensors observe different dynamic processes and send the local estimated states to a remote estimator through wireless channels, while a DoS attacker allocates its attack power on different channels as interference to reduce the wireless transmission rates, and thus degrading the estimation accuracy of the remote estimator. We consider two attack optimization problems. One is to maximize the average estimation error of different processes, and the other is to maximize the minimal one. We formulate these problems as Markov decision processes (MDPs). Unlike the majority of existing works where the attacker is assumed to have complete knowledge of the CPS, we consider an attacker with no prior knowledge of the wireless channel model and the sensor information. To address this uncertainty issue and the curse of dimensionality, we provide a learning-based attack power allocation algorithm stemming from the double deep Q-network (DDQN) method. First, with a defined partial order, the maximal elements of the action space are determined. By investigating the characteristic of the MDP, we prove that the optimal attack allocations of both problems belong to the set of these elements. This property reduces the entire action space to a smaller subset and speeds up the learning algorithm. In addition, to further improve the data efficiency and learning performance, we propose two enhanced attack power allocation algorithms which add two auxiliary tasks of MDP transition estimation inspired by model-based reinforcement learning, i.e., the next state prediction and the current action estimation. Experimental results demonstrate the versatility and efficiency of the proposed algorithms in different system settings compared with other algorithms, such as the conventional value iteration, double Q-learning, and deep Q-network.
The fit between message framing and temporal distance: An efficient way to promote an innovative product

This article presents the results of three experiments that examine the effects of the fit between message framing and construal level – induced by temporal distance – on purchase intention and willingness to pay for an innovative product (enhanced reality glasses). Generally speaking, results show that a gain-framed message associated with a long-term purchase and a loss-framed message associated with a short-term purchase are the most effective combinations for promoting an innovative product but the degree of novelty of the product and individual’s temporal orientation moderate these effects. In addition, results emphasize the mediating role of fluency to process the message.
Usability of Wearable Multiparameter Technology to Continuously Monitor Free-Living Vital Signs in People Living With Chronic Obstructive Pulmonary Disease: Prospective Observational Study

Background Vital signs monitoring (VSM) is routine for inpatients, but monitoring during free-living conditions is largely untested in chronic obstructive pulmonary disease (COPD). Objective This study investigated the usability and acceptability of continuous VSM for people with COPD using wearable multiparameter technology. Methods In total, 50 people following hospitalization for an acute exacerbation of COPD (AECOPD) and 50 people with stable COPD symptoms were asked to wear an Equivital LifeMonitor during waking hours for 6 weeks (42 days). The device recorded heart rate (HR), respiratory rate (RR), skin temperature, and physical activity. Adherence was defined by the number of days the vest was worn and daily wear time. Signal quality was examined, with thresholds of ≥85% for HR and ≥80% for RR, based on the device’s proprietary confidence algorithm. Data quality was calculated as the percentage of wear time with acceptable signal quality. Participant feedback was assessed during follow-up phone calls. Results In total, 84% of participants provided data, with average daily wear time of 11.8 (SD 2.2) hours for 32 (SD 11) days (average of study duration 76%, SD 26%). There was greater adherence in the stable group than in the post-AECOPD group (≥5 weeks wear: 71.4% vs 45.7%; P=.02). For all 84 participants, the median HR signal quality was 90% (IQR 80%-94%) and the median RR signal quality was 93% (IQR 92%-95%). The median HR data quality was 81% (IQR 58%-91%), and the median RR data quality was 85% (IQR 77%-91%). Stable group BMI was associated with HR signal quality (rs=0.45, P=.008) and HR data quality (rs=0.44, P=.008). For the AECOPD group, RR data quality was associated with waist circumference and BMI (rs=–0.49, P=.009; rs=–0.44, P=.02). In total, 36 (74%) participants in the Stable group and 21 (60%) participants in the AECOPD group accepted the technology, but 10 participants (12%) expressed concerns with wearing a device around their chest. Conclusions This wearable multiparametric technology showed good user acceptance and was able to measure vital signs in a COPD population. Data quality was generally high but was influenced by body composition. Overall, it was feasible to continuously measure vital signs during free-living conditions in people with COPD symptoms but with additional challenges in the post-AECOPD context.
Does limited EMG denervation in early primary lateral sclerosis predict amyotrophic lateral sclerosis?

Abstract Objective: We assessed whether a cohort of patients with primary lateral sclerosis (PLS) and limited electromyography (EMG) motor unit denervation changes evolve into amyotrophic lateral sclerosis (ALS) with prolonged follow-up. Methods: We initially ascertained all PLS patients diagnosed at Mayo Clinic-Rochester (1990–2016). Of 64 total cases, 43 had normal EMGs (“pure” PLS) during the first 4 years after symptom onset and were the focus of a prior publication, documenting absence of evolution to ALS. The remaining 21 patients had limited motor unit changes on EMG needle examination (denervation and most with fibrillation or fasciculation potentials) but insufficient to raise a strong suspicion of ALS; these 21 patients were followed to determine whether they evolved into ALS. Results: Of these 21 patients, the median follow-up was 7 years’ disease duration (range: 4–27 years; IQR 5–8.5). They included 11 females (52%) with median onset-age of 57 years (range: 42–72 years). Two patients (10%) subsequently met revised El Escorial criteria for ALS after 7 and 13 years, respectively. The remainder had stable EMG changes with a persistent PLS phenotype. Among these remaining 19 patients, the PLS course was somewhat more aggressive than our previously reported series of 43 patients devoid of EMG denervation. The paraparetic variant was more common than the hemiparetic and bulbar variants, similar to “pure” PLS. Conclusions: Among PLS patients with definite but limited EMG denervation, 2/21 (10%) later developed ALS. The patients in this series had a more progressive clinical course compared to our previously reported pure PLS cases.
Improved visualization of the subthalamic nucleus on synthetic MRI with optimized parameters: initial study

Background Synthetic magnetic resonance imaging (SyMRI) enables to reformat various images by adjusting the MR parameters. Purpose To investigate whether customization of the repetition time (TR), echo time (TE), and inversion time (TI) in SyMRI could improve the visualization of subthalamic nucleus (STN). Material and Methods We examined five healthy volunteers using both coronal SyMRI and quantitative susceptibility mapping (QSM), seven patients with Parkinson's disease (PD) using coronal SyMRI, and 15 patients with PD using coronal QSM. Two neuroradiologists reformatted SyMRI (optimized SyMRI) by adjusting TR, TE, and TI to achieve maximum tissue contrast between the STN and the adjacent brain parenchyma. The optimized MR parameters in the PD patients varied according to the individual. For regular SyMRI (T2-weighted imaging [T2WI] and STIR), optimized SyMRI, and QSM, qualitative visualization scores of the STN (STN score) were recorded. The contrast-to-noise ratio (CNR) of the STN was also measured. Results For the STN scores in both groups, the optimized SyMRI were significantly higher than the regular SyMRI (P < 0.05), and there were no significant differences between optimized SyMRI and QSM. For the CNR of differentiation of the STN from the substantia nigra, the optimized SyMRI was higher than the regular SyMRI (volunteer: T2WI P = 0.10 and STIR P = 0.26; PD patient: T2WI P = 0.43 and STIR P = 0.25), but the optimized SyMRI was lower than the QSM (volunteer: P = 0.26; PD patient: P = 0.03). Conclusions On SyMRI, optimization of MR parameters (TR, TE, and TI) on an individual basis may be useful to increase the conspicuity of the STN.
Effect of cancer on outcome of COVID-19 patients: a systematic review and meta-analysis of studies of unvaccinated patients

Background: Since the beginning of the SARS-CoV-2 pandemic, cancer patients affected by COVID-19 have been reported to experience poor prognosis; however, a detailed quantification of the effect of cancer on outcome of unvaccinated COVID-19 patients has not been performed. Methods: To carry out a systematic review of the studies comparing the outcome of unvaccinated COVID-19 patients with and without cancer, a search string was devised which was used to identify relevant publications in PubMed up to December 31, 2020. We selected three outcomes: mortality, access to ICU, and COVID-19 severity or hospitalization. We considered results for all cancers combined as well as for specific cancers. We conducted random-effects meta-analyses of the results, overall and after stratification by region. We also performed sensitivity analyses according to quality score and assessed publication bias. Results: For all cancer combined, the pooled odds ratio (OR) for mortality was 2.32 (95% confidence interval [CI] 1.82–2.94, I2 for heterogeneity 90.1%, 24 studies), that for ICU admission was 2.39 (95% CI 1.90–3.02, I2 0.0%, 5 studies), that for disease severity or hospitalization was 2.08 (95% CI 1.60–2.72, I2 92.1%, 15 studies). The pooled mortality OR for hematologic neoplasms was 2.14 (95% CI 1.87–2.44, I2 20.8%, 8 studies). Data were insufficient to perform a meta-analysis for other cancers. In the mortality meta-analysis for all cancers, the pooled OR was higher for studies conducted in Asia than studies conducted in Europe or North America. There was no evidence of publication bias. Conclusions: Our meta-analysis indicates a twofold increased risk of adverse outcomes (mortality, ICU admission, and severity of COVID-19) in unvaccinated COVID-19 patients with cancer compared to COVID-19 patients without cancer. These results should be compared with studies conducted in vaccinated patients; nonetheless, they argue for special effort to prevent SARS-CoV-2 infection in patients with cancer. Funding: No external funding was obtained.
Prepare for Ludicrous Speed: Marker-based Instantaneous Binocular Rolling Shutter Localization

— We propose a marker-based geometric framework for the high-frequency absolute 3D pose estimation of a binocular camera system by using the data captured during the exposure of a single rolling shutter scanline. In contrast to existing approaches enforcing temporal or motion models among scanlines (e.g. linear motion, constant velocity or small motion assumptions), we strive to determine the pose from instantaneous binocular capture (i.e. without using data from previous scanlines) and achieve drift-free pose estimation. We leverage the projective invariants of a novel rigid planar pattern, to both define a geometric reference as well as to determine 2D-3D correspondences from raw edge detection measurements from individual scanlines. Moreover, to tackle the ensuing multi-view estimation problem, achieve real-time operation, and minimize latency, we develop a pair of custom solvers leveraging our geometric setup. To mitigate sensitivity to noise, we propose a geometrically consistent measurement refinement mechanism. We verify the quality of our solvers by comparing with state of the art general solvers for absolute pose estimation of generalized cameras. Finally, we demonstrate the effectiveness of our proposed approach with an FPGA-based implementation which achieves a localization throughput of 129.6 KHz with a 1.5 µ s latency.
Minimum-Norm Estimation of TMS-Activated Motor Cortical Sites in Realistic Head and Brain Geometry

Navigated transcranial magnetic stimulation (nTMS) is a widely used tool for motor cortex mapping. However, the full details of the activated cortical area during the mapping remain unknown due to the spread of the stimulating electric field (E-field). Computational tools, which combine the E-field with physiological responses, have potential for revealing the activated source area. We applied the minimum-norm estimate (MNE) method in a realistic head geometry to estimate the activated cortical area in nTMS motor mappings of the leg and hand muscles. We calculated the MNE also in a spherical head geometry to assess the effect of the head model on the MNE maps. Finally, we determined optimized coil placements based on the MNE map maxima and compared these placements with the initial hotspot placement. The MNE maps generally agreed well with the original motor maps: in the realistic head geometry, the distance from the MNE map maximum to the motor map center of gravity (CoG) was 8.8 ± 4.6 mm in the leg motor area and 6.6 ± 2.5 mm in the hand motor area. The head model did not have a significant effect on these distances; however, it had a significant effect on the distance between the MNE CoG and the motor map ( ${p} < 0.05$ ). The optimized coil locations were < 1 cm from the initial hotspot in 7/10 subjects. Further research is required to determine the level of anatomical detail and the optimal mapping parameters required for robust and accurate localization.
Early Childhood Sleep Trajectories and Association with Maternal Depression: A Prospective Cohort Study.

STUDY OBJECTIVES To investigate trajectories of early childhood sleep in the first three years and association with maternal depressive symptoms. METHODS Data was from 243 Chinese mother-child dyads. Children's sleep duration and night-waking were assessed using the Brief Infant Sleep Questionnaire (BISQ) at 42 days, 3, 6, 9, 12, 18, 24, and 36 months postpartum. The Center for Epidemiological Survey-Depression Scale (CES-D), Edinburgh Postnatal Depression Scale (EPDS), and Profile of Mood States (POMS) were used to assess maternal depressive symptoms at late pregnancy, 42 days, and 36 months postpartum, respectively. Early childhood sleep trajectories were estimated with group-based trajectory models. The association between early childhood sleep trajectories and maternal depressive symptoms were examined with binary and multinomial logistic regression models and linear regression models. RESULTS Three trajectories of daytime sleep duration ("short", 14.4%; "medium", 60.4%; "long", 25.2%), nighttime sleep duration ("increasing", 17.6%; "stable",76.3%; "decreasing",6.1%), and total sleep duration ("short", 21.5%; "medium", 59.9%; "long",18.6%), and two trajectories of night-waking ("resolving", 22.9%; "persistent", 77.1%) were identified. Controlling for confounding factors, maternal depression at 42 days postpartum was associated with higher risks for short daytime sleep duration and persistent night-waking in children. Persistent night-waking in children was associated with increased maternal depressive symptoms at 36 months postpartum. CONCLUSION Early childhood sleep follows distinct trajectories in the first three years of life. The trajectories of short daytime sleep duration and persistent night-waking are associated with maternal depression. The findings indicate tailored interventions should target both unfavorable early childhood sleep trajectories and maternal depression.
The utility of a standardised breath sampler in school age children within a real-world prospective study

Clinical assessment of children with asthma is problematic, and non-invasive biomarkers are needed urgently. Monitoring exhaled volatile organic compounds (VOCs) is an attractive alternative to invasive tests (blood and sputum) and may be used as frequently as required. Standardised reproducible breath-sampling is essential for exhaled-VOC analysis, and although the ReCIVA (Owlstone Medical Limited) breath-sampler was designed to satisfy this requirement, paediatric use was not in the original design brief. The efficacy of the ReCIVA at sampling breath from children has been studied, and 90 breath-samples from 64 children (5–15 years) with, and without asthma (controls), were collected with two different ReCIVA units. Seventy samples (77.8%) contained the specified 1 l of sampled-breath. Median sampling times were longer in children with acute asthma (770.2 s, range: 532.2–900.1 s) compared to stable asthma (690.6 s, range: 477.5–900.1 s; p = 0.01). The ReCIVA successfully detected operational faults, in 21 samples. A leak, caused by a poor fit of the face mask seal was the most common (15); the others were USB communication-faults (5); and, a single instance of a file-creation error. Paediatric breath-profiles were reliably monitored, however synchronisation of sampling to breathing-phases was sometimes lost, causing some breaths not to be sampled, and some to be sampled continuously. This occurred in 60 (66.7%) of the samples and was a source of variability. Importantly, multi-variate modelling of untargeted VOC analysis indicated the absence of significant batch effects for eight operational variables. The ReCIVA appears suitable for paediatric breath-sampling. Post-processing of breath-sample meta-data is recommended to assess the quality of sample-acquisition. Further, future studies should explore the effect of pump-synchronisation faults on recovered VOC profiles, and mask sizes to fit all ages will reduce the potential for leaks and importantly, provide higher levels of comfort to children with asthma.