Miracle-dz/UniFAR-FTUs huggingface dataset:
Cost-effectiveness analysis of patent foramen ovale closure versus medical therapy alone after cryptogenic stroke

Background Closure of a patent foramen ovale reduces the risk of recurrent stroke compared with medical therapy alone in young patients with cryptogenic strokes revealed by randomized control trials. Some cost-effectiveness analyses outside Japan have shown that patent foramen ovale closure is cost-effective, but no studies have examined cost-effectiveness in Japan. The objective of this study is to assess cost-effectiveness, from the perspective of a Japanese healthcare payer, of patent foramen ovale closure versus medical therapy alone for the patients with patent foramen ovale related cryptogenic strokes. Methods A cost-effectiveness study was conducted by developing a decision tree and a Markov model. Probabilities and a 5.9-year time horizon followed the RESPECT study. Utilities and costs were based upon published studies and assumptions. The model cycle was one month. All assumptions were assessed by experts, including a cardiologist and a statistical expert. The target population comprised patients with cryptogenic stroke and patent foramen ovale, aged 60 years or younger. Incremental cost-effectiveness ratio was evaluated. Then one-way sensitivity analyses and probabilistic sensitivity analyses were conducted to assess robustness. Results Incremental cost-effectiveness ratio of patent foramen ovale closure compared with medical therapy was estimated at 3,318,152 yen per quality-adjusted life years gained. One-way sensitivity analysis showed that the stable state utility score difference between patent foramen ovale closure and medical therapy had the largest impact on incremental cost-effectiveness ratio. Patent foramen ovale closure is cost-effective at a stable state utility score difference of >0.051, compared with medical therapy. Probabilistic sensitivity analyses demonstrated that patent foramen ovale closure was 50.3% cost-effective with a willingness-to-pay threshold of 5,000,000 yen / quality-adjusted life years. Conclusions From a healthcare payer perspective, patent foramen ovale closure may be cost-effective compared with medical therapy for Japanese patients with cryptogenic stroke who were under 60 years.
Wireless, Battery-Free, and Fully Implantable Micro-Coil System for 7 T Brain MRI

An elegant solution for the concurrent transmission of data and power is essential for implantable wireless magnetic resonance imaging (MRI). This paper presents a self-tuned open interior microcoil (MC) antenna with three useful operating bands of 300 (7 T), 400, and 920 MHz, for blood vessel imaging, data telemetry, and efficient wireless transmission of power, respectively. The proposed open interior MC antenna contains two mirrorlike arms with diameters and lengths of 2.4 mm and 9.8 mm, respectively, to avoid blood flow blockage. To wirelessly show LED glow on a saline based phantom, the MC was fabricated on a flexible polyimide material and combined with a miniaturized rectifier and a micro-LED. Using a path gain, the power transfer efficiency (PTE) of the MC rotation was also analyzed. Additionally, the PTE was calculated for a range of distances between 25 and 60 mm, and a −27.1 dB PTE attained at a distance of of 30 mm. Based on the recommendations of the International Commission on Non-Ionizing Radiation Protection for human brain safety when exposed to radio-frequencies from external transmitter, a specific absorption rate analysis was analyzed. Measurements of the s-parameters were noted using a saline solution and blood vessel model to imitate a realistic human head. They were found to correlate reasonably with the simulated results.
Efficacy and safety of FOLFIRI/aflibercept (FA) in an elderly population with metastatic colorectal cancer (mCRC) after failure of an oxaliplatin-based regimen

Background The VELOUR study showed the benefit of FOLFIRI-Aflibercept (FA) versus FOLFIRI in patients with metastatic colorectal cancer (mCRC) in second-line treatment. However, only 36% of the included patients were ≥65 years. Thus, we seek to evaluate the efficacy and safety of FA in the elderly population in the context of routine practice. Materials and methods We conducted an observational, retrospective, multicenter, observational study of patients ≥70 years with mCRC treated with FA after progression to oxaliplatin chemotherapy in routine clinical practice in 9 hospitals of the GITuD group. Results Of 388 patients treated with FA between June 2013 and November 2018, 75 patients ≥70 years were included. The median number of cycles was 10 and the objective response (ORR) and disease control rates (DCR) were 33.8% and 72.0%, respectively. With a median follow-up of 27.1 months, median Progression-free survival (PFS) was 6.6 months and median Overall Survival (OS) was 15.1 months. One third fewer metastasectomies were performed in the ≥75 years’ subgroup (24 vs. 52%, p = 0.024) and more initial FOLFIRI dose reductions (68 vs. 36%, p = 0.014). ORR (23.8% vs. 38.3%), DCR (42.8% vs. 85.1%), and PFS (4 vs. 7.8 months; p = 0.017) were significantly less, without difference in OS (9.9 vs. 17.1 months; p = 0.129). The presence of prior hypertension (HT) (PFS 7.9 vs. 5.7 months, p = 0.049) and HT ≥ grade 3 during treatment (PFS 7.6 vs. 6.6 months, p = 0.024) were associated with longer PFS. The most frequent grade 3/4 adverse events were: asthenia (21.3%), neutropenia (14.7%), and diarrhea (14.7%). 57.3% required FOLFIRI dose reduction; 34.7% of aflibercept, including discontinuation (5.3% and 18.7%, respectively). Conclusions FA combination is effective in patients ≥70 years. The occurrence of HT is predictive of efficacy. Close monitoring of toxicity and initial dose adjustment is recommended.
Continuous surveillance of drug-resistant TB burden in Rwanda: a retrospective cross-sectional study

Abstract Background Since the roll-out of the Xpert MTB/RIF assay, continuous surveillance can provide an estimate of rifampicin-resistant TB (RR-TB) prevalence, provided high drug susceptibility testing (DST) coverage is achieved. We use national data from Rwanda to describe rifampicin DST coverage, estimate the prevalence of RR-TB and assess its predictors. Methods Routinely collected DST data were entered into an electronic TB case-based surveillance system. DST coverage was calculated among all bacteriologically confirmed pulmonary TB patients notified from 1 July 2019 to 30 June 2020 in Rwanda. The prevalence of RR-TB was estimated among those with DST results. Univariable and multivariable analysis was performed to explore predictors for RR TB. Results Among 4066 patients with bacteriologically confirmed pulmonary TB, rifampicin DST coverage was 95.6% (4066/4251). RR-TB was diagnosed in 73 patients. The prevalence of RR-TB was 1.4% (53/3659; 95% CI 1.09 to 1.89%) and 4.9% (20/406; 95% CI 3.03 to 7.51%) in new and previously treated TB cases, respectively. Predictors of RR-TB were: (1) living in Kigali City (adjusted OR [aOR] 1.65, 95% CI 1.03 to 2.65); (2) previous TB treatment (aOR 3.64, 95% CI 2.14 to 6.19); and (3) close contact with a known RR-TB patient (aOR 11.37, 95% CI 4.19 to 30.82). Conclusions High rifampicin DST coverage for routine reporting allowed Rwanda to estimate the RR-TB prevalence among new and previously treated patients.
Metabolic activity diffusion imaging (MADI): II. Noninvasive, high‐resolution human brain mapping of sodium pump flux and cell metrics

We introduce a new 1H2O magnetic resonance approach: metabolic activity diffusion imaging (MADI). Numerical diffusion‐weighted imaging decay simulations characterized by the mean cellular water efflux (unidirectional) rate constant (kio), mean cell volume (V), and cell number density (ρ) are produced from Monte Carlo random walks in virtual stochastically sized/shaped cell ensembles. Because of active steady‐state trans‐membrane water cycling (AWC), kio reflects the cytolemmal Na+, K+ATPase (NKA) homeostatic cellular metabolic rate (cMRNKA). A digital 3D “library” contains thousands of simulated single diffusion‐encoded (SDE) decays. Library entries match well with disparate, animal, and human experimental SDE decays. The V and ρ values are consistent with estimates from pertinent in vitro cytometric and ex vivo histopathological literature: in vivo V and ρ values were previously unavailable.
PLGA-based microspheres containing ropivacaine and betamethasone for sciatic nerve block in mice

Abstract The aim of the present study was to develop Poly (lactic-co-glycolic acid) (PLGA)-based microspheres containing ropivacaine and betamethasone (RPC/BTM PLGA MS) by emulsion-solvent evaporation method. RPC/BTM PLGA MS were characterized by physical properties, such as morphology and particle size, and in vitro drug release. In addition, in vivo pharmacokinetics and pharmacodynamics of RPC/BTM PLGA MS were also investigated. The prepared RPC/BTM PLGA MS was suitable for local injection with a well-dispersed spherical shape, high stability, and high encapsulation efficiency. The mean diameter was 14.8 ± 1.2 µm and the polydispersity index (PDI) was 0.32 ± 0.04. In an in vitro study of drug release, it can be concluded that the RPC/BTM PLGA MS exhibited sustained and long-term release properties for 16 days. Furthermore, the result of an in vivo study indicated that the RPC/BTM PLGA MS had sustained release effect and the pharmacodynamics result showed that preparing RPC/BTM PLGA MS as microsphere preparation could not only extend the drug effect time but also prolong the duration of local anesthetics compared with the common RPC PLGA MS.
Structural and biophysical characterization of the multidomain xylanase Xyl

The depletion of fossil fuels, associated pollution, and resulting health hazards are of concern worldwide. Woody biomass constitutes an alternative source of cleaner and renewable energy. The efficient use of woody biomass depends on xylan depolymerisation as the endo-β-1,4-xylopyranosyl homopolymer is the main component of hemicellulose, the second most abundant component of wood. Xylan depolymerisation is achieved by hemicellulolytic xylanases of glycoside hydrolase (GH) families 5, 8, 10, 11, 30 and 43 of the CAZY database. We analysed a multidomain xylanase (Xyl) from the hindgut metagenome of the snouted harvester termite Trinervitermes trinervoides that releases xylobiose and xylotriose from beech and birch xylan and wheat arabinoxylan. The four domains of Xyl include an N-terminal GH11 xylanase domain, two family 36-like carbohydrate-binding domains CBM36-1 and 2, and a C-terminal CE4 esterase domain. Previous analyses indicated that CBM36-1 deletion slightly increased GH11 catalysis at low pH whereas removal of both CBMs decreased xylanase activity at 60°C from 90 to 56%. Possible cooperativity between the domains suggested by these observations was explored. A crystal structure of the two-domain construct, GH11-CBM36-1, confirmed the structure of the GH11 domain whereas the CBM36-1 domain lacked electron density, possibly indicating a random orientation of the CBM36-1 domain around the GH11 domain. Isothermal titration calorimetry (ITC) experiments similarly did not indicate specific interactions between the individual domains of Xyl supporting a “beads-on-a-string” model for Xyl domains.
EEG-based vibrotactile evoked brain-computer interfaces system: A systematic review

Recently, a novel electroencephalogram-based brain-computer interface (EVE-BCI) using the vibrotactile stimulus shows great potential for an alternative to other typical motor imagery and visual-based ones. (i) Objective: in this review, crucial aspects of EVE-BCI are extracted from the literature to summarize its key factors, investigate the synthetic evidence of feasibility, and generate recommendations for further studies. (ii) Method: five major databases were searched for relevant publications. Multiple key concepts of EVE-BCI, including data collection, stimulation paradigm, vibrotactile control, EEG signal processing, and reported performance, were derived from each eligible article. We then analyzed these concepts to reach our objective. (iii) Results: (a) seventy-nine studies are eligible for inclusion; (b) EEG data are mostly collected among healthy people with an embodiment of EEG cap in EVE-BCI development; (c) P300 and Steady-State Somatosensory Evoked Potential are the two most popular paradigms; (d) only locations of vibration are heavily explored by previous researchers, while other vibrating factors draw little interest. (e) temporal features of EEG signal are usually extracted and used as the input to linear predictive models for EVE-BCI setup; (f) subject-dependent and offline evaluations remain popular assessments of EVE-BCI performance; (g) accuracies of EVE-BCI are significantly higher than chance levels among different populations. (iv) Significance: we summarize trends and gaps in the current EVE-BCI by identifying influential factors. A comprehensive overview of EVE-BCI can be quickly gained by reading this review. We also provide recommendations for the EVE-BCI design and formulate a checklist for a clear presentation of the research work. They are useful references for researchers to develop a more sophisticated and practical EVE-BCI in future studies.
Future directions for precision oncology in prostate cancer

Clinical genomic testing is becoming routine in prostate cancer, as biomarker‐driven therapies such as poly‐ADP ribose polymerase (PARP) inhibitors and anti‐PD1 immunotherapy are now approved for select men with castration‐resistant prostate cancer harboring alterations in DNA repair genes. Challenges for precision medicine in prostate cancer include an overall low prevalence of actionable genomic alterations and a still limited understanding of the impact of tumor heterogeneity and co‐occurring alterations on treatment response and outcomes across diverse patient populations. Expanded tissue‐based technologies such as whole‐genome sequencing, transcriptome analysis, epigenetic analysis, and single‐cell RNA sequencing have not yet entered the clinical realm and could potentially improve upon our understanding of how molecular features of tumors, intratumoral heterogeneity, and the tumor microenvironment impact therapy response and resistance. Blood‐based technologies including cell‐free DNA, circulating tumor cells (CTCs), and extracellular vesicles (EVs) are less invasive molecular profiling resources that could also help capture intraindividual tumor heterogeneity and track dynamic changes that occur in the context of specific therapies. Furthermore, molecular imaging is an important biomarker tool within the framework of prostate cancer precision medicine with a capability to detect heterogeneity across metastases and potential therapeutic targets less invasively. Here, we review recent technological advances that may help promote the future implementation and value of precision oncology testing for patients with advanced prostate cancer.
A meta-analysis of the Masquelet technique and the Ilizarov bone transport method for the treatment of infected bone defects in the lower extremities

Purpose:To compare the clinical outcomes of the Masquelet technique and Ilizarov bone transport method for the treatment of patients with infected bone defects in the lower extremities. Methods: Eligible studies were searched from six databases until 12 April 2021. Data extraction was independently conducted by two investigators, which was followed by a quality assessment. Weighted mean difference (WMD) and 95% confidence interval (CI) were used to analyze continuous variables, while odds ratio (OR) and 95% CI were used to analyze categorical variables. All statistical analyses were conducted using RevMan 5.3 and Stata 12.0. Results: Thirteen articles were included in this meta-analysis. There was a significant difference observed in hospitalization costs (WMD [95% CI] = −1.75 [−2.50, −0.99] thousand US dollar, p < 0.00,001), final union time (WMD [95% CI] = −4.54 [−6.91, −2.17] months, p = 0.0002), time to full weight bearing (WMD [95% CI] = −1.73 [−3.36, −0.10] months, p = 0.04), quality of life (WMD [95% CI] = 7.70 [4.74, 10.67], p < 0.00,001), and the risk of complications (OR [95%CI] = 0.39 [0.19, 0.79], p = 0.009) between the Masquelet and Ilizarov groups. No significant differences in other outcomes were observed between the two groups. Conclusion: Masquelet technique exhibited the advantages in the lower hospitalization cost, shorter final union time, shorter time to full weight bearing, lower rate of complications, and better post-operative quality of life, compared with Ilizarov bone transport method. However, this finding should be confirmed in large-scale clinical samples.
Mirror visual feedback during unilateral finger movements is related to the desynchronization of cortical electroencephalographic somatomotor alpha rhythms

Abstract Using a mirror adequately oriented, the motion of just one hand induces the illusion of the movement with the other hand. Here, we tested the hypothesis that such a mirror phenomenon may be underpinned by an electroencephalographic (EEG) event‐related desynchronization/synchronization (ERD/ERS) of central alpha rhythms (around 10 Hz) as a neurophysiological measure of the interactions among cerebral cortex, basal ganglia, and thalamus during movement preparation and execution. Eighteen healthy right‐handed male participants performed standard auditory‐triggered unilateral (right) or bilateral finger movements in the No Mirror (M−) conditions. In the Mirror (M+) condition, the unilateral right finger movements were performed in front of a mirror oriented to induce the illusion of simultaneous left finger movements. EEG activity was recorded from 64 scalp electrodes, and the artifact‐free event‐related EEG epochs were used to compute alpha ERD. In the M− conditions, a bilateral prominent central alpha ERD was observed during the bilateral movements, while left central alpha ERD and right alpha ERS were seen during unilateral right movements. In contrast, the M+ condition showed significant bilateral and widespread alpha ERD during the unilateral right movements. These results suggest that the above illusion of the left movements may be related to alpha ERD measures reflecting excitatory desynchronizing signals in right lateral premotor and primary somatomotor areas possibly in relation to basal ganglia‐thalamic loops.
Maternal type 1 diabetes, pre-term birth and risk of autism spectrum disorder–a prospective cohort study

Abstract Background It has been suggested that maternal type 1 diabetes (T1D) increases the risk of autism spectrum disorder (ASD) in the offspring. However, it is unclear whether this risk is mediated by pre-term birth, affecting around one-third of pregnancies with T1D, and whether maternal levels of glycated haemoglobin (HbA1c) impact the risk. Methods A cohort of 1.4 million Swedish children born between 1998 and 2015, and their parents. Maternal T1D and HbA1c before or in early pregnancy, gestational and ASD diagnoses were obtained from Swedish national registers. Relative risk (RR) and 95% CIs of ASD were estimated by hazard ratios (HRs) from Cox regression or RR from log-binomial regression. Results Of 1 406 650 children, 8003 (0.6%) were born to mothers with T1D, 24 941 (1.8%) were diagnosed with ASD and 81 915 (5.8%) were born pre-term. The risk of ASD was increased in offspring of mothers with T1D was HR = 1.40 (1.21–1.61). The RR for each +5-mmol/mol excess HbA1c was estimated at HR = 1.03 (0.97–1.10). The T1D effect on ASD mediated through pre-term birth was estimated at RR = 1.06 (1.05 to 1.08), corresponding to 22% (16% to 41%) of the total effect. T1D in pregnancy was associated with increased ASD risk in the offspring. Twenty percent of the total effect was accounted for by pre-term birth. HbA1c was not associated with ASD risk, beyond the risk associated by the T1D diagnosis itself. Conclusion Awareness of ASD in the offspring of mothers with T1D may be warranted, especially considering the additional effect of pre-term birth.
Impact of early use of long-acting injectable antipsychotics on functional outcome in first episode psychosis: a 3-year longitudinal study

Abstract Objectives To describe, in a naturalistic setting, the impact of the early use of LAI-AP on functional outcomes of early psychosis patients as compared to oral antipsychotics (OAP). Methods Longitudinal prospective 3-year naturalistic study of all consecutive admissions (n = 416) to two Early intervention services (EIS) for psychosis comparing baseline characteristics and the evolution of global functioning, occupation (work and studies), and living arrangements autonomy according to the route of administration of the antipsychotic medication. The cohort was divided into four groups: LAI-AP first (started on LAI-AP and later received OAP), OAP first, LAI-AP only, and OAP only. Results Global assessment of functioning (GAF) improved in all groups, but our mixed-effect model did not show any significant association between the route of administration and the GAF outcome. The LAI-AP only group was significantly less likely to have extreme residential instability at 3 years than the other groups despite its highest proportion of homeless youth and their poor prognostic factors at baseline. Conclusions Our naturalistic study suggests a significant protective effect of LAI-AP on extreme residential instability for the most vulnerable patients, but no impact of the first AP administration route on other functional outcomes was observed at 3 years of follow-up. Key points Long-acting injectable antipsychotics seem promising to avoid extreme residential instability in early psychosis. Global assessment of functioning (GAF) improved in all groups. There was no significant association between the first route of administration and global functionning.
Vomiting and Gastric Motility in Early Brain Damaged Children With Congenital Zika Syndrome

Objectives: This study investigated the occurrence of vomiting and gastric dysmotility in dysphagic children with congenital Zika syndrome (CZS) and assessed possible associations of these findings with the severity of dysphagia and the presence of tube feeding. Methods: Forty-six children with CZS were assessed for dysphagia, and the occurrence of vomiting, dietary volume tolerance <15 mL/kg, and feeding time per meal >30 minutes were evaluated. Gastric antrum ultrasonography was used to detect the frequency of contractions and measure antral areas (at fasting and 15 minutes postprandial), from which the gastric emptying rate (GER) was calculated. Antral ultrasonography findings were compared with those of ten healthy controls. Vomiting and gastric motility were compared between CZS patients according to the severity of dysphagia and the requirement for tube feeding. Results: Overall, 76% (35/46) of children with CZS had moderate-to-severe dysphagia (MSD), among whom 60% (21/35) were tube fed [MSD tube fed (MSDTF)]. Vomiting occurred in 54% (25/46) of children, whereas dietary volume intolerance and prolonged feeding time were observed in 59% (27/46) and 37% (17/46), respectively, most frequently in MSDTF patients. On ultrasound, 61% (28/46) of children with CZS had no antral contractions, whereas 90% (9/10) of controls did. Compared to healthy controls, GER was eight-fold lower in children with CZS and 60-fold lower in MSDTF children. Conclusions: In dysphagic children with CZS, vomiting, volume intolerance, and prolonged feeding time were frequent and possibly associated with impaired antral contraction and delayed gastric emptying, especially in cases of severe dysphagia and tube feeding.