Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-Term Outcomes of Previously Treated Adult and Adolescent Patients with Severe Hemophilia A Receiving Prophylaxis with Extended Half-Life FVIII Treatments: An Economic Analysis from a United Kingdom Perspective

Background The standard of care for patients with hemophilia A is prophylaxis with factor VIII (FVIII) therapies. Extended half-life (EHL) FVIII products offer a reduced infusion burden compared with standard FVIII treatments. However, comparative evidence between EHLs is lacking. Objective To develop a pharmacodynamic–pharmacokinetic decision model to predict comparative bleed outcomes of adolescents and adults with hemophilia A receiving treatment with various EHL FVIII therapies, capturing differences in cumulative bleeding episodes, breakthrough bleed resolution and resource costs, as well as quality-adjusted life years (QALYs). Methods The patient population from the pathfinder 2 Phase III clinical trial was used to understand the link between FVIII levels and annual bleeding rates (ABRs). Pharmacokinetic/pharmacodynamic modeling was subsequently applied to estimate FVIII levels for four EHL FVIII treatments (turoctocog alfa pegol [Esperoct®], rurioctocog alfa pegol [Adynovi®], efmoroctocog alfa [Elocta®], and damoctocog alfa pegol [Jivi®]) to predict comparative ABRs. FVIII consumption costs (due to prophylactic treatment and breakthrough bleed resolution) and resource costs, as well as QALYs, were subsequently estimated from a UK NHS perspective over a 70-year time horizon. Results Turoctocog alfa pegol prophylaxis resulted in 8–19% fewer cumulative bleeding episodes versus comparators in the base case scenario. Assuming parity in annual prophylaxis costs, turoctocog alfa pegol prophylaxis reduced the cost of product and resource use to resolve a breakthrough bleed by 9–25% versus comparators. Prophylaxis with turoctocog alfa pegol was also associated with the most QALYs, representing a discounted QALY gain of 0.35–1.05 compared with the other treatments. Conclusion Using a pharmacodynamic–pharmacokinetic decision model, turoctocog alfa pegol prophylaxis was associated with fewer cumulative bleeds, as well as lower product and resource costs related to resolving a breakthrough bleed and most QALYs versus comparators.
PD-1 Expression in Pre-Treatment Follicular Lymphoma Predicts the Risk of Subsequent High-Grade Transformation

Purpose Follicular lymphoma (FL) is an indolent, yet generally incurable neoplasia with a median survival exceeding 10 years. However, a subset of FL patients experiences histological transformation (HT) to a more aggressive lymphoma, in the majority of cases to diffuse large B-cell lymphoma (DLBCL). This affects both the clinical course and the prognostic outcome, resulting in a markedly reduced survival after transformation. Thus, early risk stratification and prediction of patients at risk of HT would be highly valuable in the clinical setting. Here, we investigated the potential of the immune inhibitory programmed death 1 (PD-1) receptor as a biomarker predictive of HT. Patients and Methods Immunohistochemical staining and quantification by digital image analysis of PD-1 was performed on diagnostic tumor-tissue samples from FL patients with and without subsequent transformation (n=34 and n=46, respectively), and on paired samples from the transformed lymphoma (n=34). Results At the time of initial FL diagnosis, samples from patients with subsequent HT had significantly higher tumor-tissue expression of PD-1 compared with diagnostic FL samples from patients without subsequent HT (p=0.010). At the time of transformation, PD-1 expression was significantly reduced (p<0.001). No difference was observed in intra-follicular PD-1 expression at FL diagnosis between samples from patients with or without HT; however, high intra-follicular levels of PD-1 were associated with significantly shorter transformation-free survival times (p<0.043). Conclusion Our data suggest that pre-treatment tumor-tissue PD-1 expression already predicts the risk of subsequent transformation to DLBCL, as early as the time of FL diagnosis.
Nodding syndrome, many questions remain but we can prevent it by eliminating onchocerciasis

In their concise review about nodding syndrome, the authors discussed several potential aetiological factors and concluded that the cause is still unknown (Olum et al., 2020). We agree that the pathogenesis of this syndrome remains to be elucidated. However, recent research, not mentioned in the review, showed that nodding syndrome appears in regions with high Onchocerca volvulus transmission and disappears when onchocerciasis is eliminated from those areas. This was evidently demonstrated by two recent studies in Uganda. The first study was conducted in an onchocerciasis endemic region in northern Uganda, in the districts Kitgum and Pader. In the early 2000s, these districts experienced a nodding syndrome epidemic in addition to an overall increase of epilepsy. Based on the results of an epilepsy survey performed in 2012 and another in 2017, we showed that new cases of nodding syndrome stopped appearing after consistent implementation of biannual ivermectin distribution and ground larviciding of rivers (Gumisiriza et al., 2020b). The second study was performed in Kabende, in western Uganda. In 1991, a high prevalence of epilepsy and cases of nodding syndrome had been reported in this onchocerciasis endemic region (Kaiser et al., 1996). In 2018, during an epilepsy survey in the same area, it was found that nodding syndrome had stopped to appear and that the overall prevalence and incidence of epilepsy also had dropped significantly after the elimination of onchocerciasis in 2004 (Gumisiriza et al., 2020a). It is important to mention that nodding syndrome has now been reported in many other onchocerciasis-endemic areas besides the three countries (Tanzania, South Sudan, and Uganda) where nodding syndrome was initially described. These other countries include Cameroon (Siewe et al., 2019), the Democratic Republic of Congo (Colebunders et al., 2016) and Liberia (Siewe Fodjo et al., 2020). It is common for persons with nodding syndrome to have siblings correspondingly suffering other forms of epilepsy within the household. This is especially observed among families living near the breeding sites of the blackflies (the vectors of onchocerciasis) (Colebunders et al., 2016). Therefore, nodding syndrome should be considered as one of the phenotypic manifestations of onchocerciasis-associated epilepsy (Colebunders et al., 2019). The association between onchocerciasis and epilepsy was already reported in 1938 by Casis (1938) in Mexico. The magnitude of the disease burden caused by onchocerciasis-associated epilepsy needs to be internationally recognized. A delay in the implementation of adequate onchocerciasis elimination in hotspot areas will result in the continued development of nodding syndrome and other forms of epilepsy among children.
FFU-Net: Feature Fusion U-Net for Lesion Segmentation of Diabetic Retinopathy

Diabetic retinopathy is one of the main causes of blindness in human eyes, and lesion segmentation is an important basic work for the diagnosis of diabetic retinopathy. Due to the small lesion areas scattered in fundus images, it is laborious to segment the lesion of diabetic retinopathy effectively with the existing U-Net model. In this paper, we proposed a new lesion segmentation model named FFU-Net (Feature Fusion U-Net) that enhances U-Net from the following points. Firstly, the pooling layer in the network is replaced with a convolutional layer to reduce spatial loss of the fundus image. Then, we integrate multiscale feature fusion (MSFF) block into the encoders which helps the network to learn multiscale features efficiently and enrich the information carried with skip connection and lower-resolution decoder by fusing contextual channel attention (CCA) models. Finally, in order to solve the problems of data imbalance and misclassification, we present a Balanced Focal Loss function. In the experiments on benchmark dataset IDRID, we make an ablation study to verify the effectiveness of each component and compare FFU-Net against several state-of-the-art models. In comparison with baseline U-Net, FFU-Net improves the segmentation performance by 11.97%, 10.68%, and 5.79% on metrics SEN, IOU, and DICE, respectively. The quantitative and qualitative results demonstrate the superiority of our FFU-Net in the task of lesion segmentation of diabetic retinopathy.
Αlpha 5 subunit-containing GABAA receptors in temporal lobe epilepsy with normal MRI

Abstract GABAA receptors containing the α5 subunit mediate tonic inhibition and are widely expressed in the limbic system. In animals, activation of α5-containing receptors impairs hippocampus-dependent memory. Temporal lobe epilepsy is associated with memory impairments related to neuron loss and other changes. The less selective PET ligand [11C]flumazenil has revealed reductions in GABAA receptors. The hypothesis that α5 subunit receptor alterations are present in temporal lobe epilepsy and could contribute to impaired memory is untested. We compared α5 subunit availability between individuals with temporal lobe epilepsy and normal structural MRI (‘MRI-negative’) and healthy controls, and interrogated the relationship between α5 subunit availability and episodic memory performance, in a cross-sectional study. Twenty-three healthy male controls (median ± interquartile age 49 ± 13 years) and 11 individuals with MRI-negative temporal lobe epilepsy (seven males; 40 ± 8) had a 90-min PET scan after bolus injection of [11C]Ro15-4513, with arterial blood sampling and metabolite correction. All those with epilepsy and six controls completed the Adult Memory and Information Processing Battery on the scanning day. ‘Bandpass’ exponential spectral analyses were used to calculate volumes of distribution separately for the fast component [VF; dominated by signal from α1 (α2, α3)-containing receptors] and the slow component (VS; dominated by signal from α5-containing receptors). We made voxel-by-voxel comparisons between: the epilepsy and control groups; each individual case versus the controls. We obtained parametric maps of VF and VS measures from a single bolus injection of [11C]Ro15-4513. The epilepsy group had higher VS in anterior medial and lateral aspects of the temporal lobes, the anterior cingulate gyri, the presumed area tempestas (piriform cortex) and the insulae, in addition to increases of ∼24% and ∼26% in the ipsilateral and contralateral hippocampal areas (P < 0.004). This was associated with reduced VF:VS ratios within the same areas (P < 0.009). Comparisons of VS for each individual with epilepsy versus controls did not consistently lateralize the epileptogenic lobe. Memory scores were significantly lower in the epilepsy group than in controls (mean ± standard deviation −0.4 ± 1.0 versus 0.7 ± 0.3; P = 0.02). In individuals with epilepsy, hippocampal VS did not correlate with memory performance on the Adult Memory and Information Processing Battery. They had reduced VF in the hippocampal area, which was significant ipsilaterally (P = 0.03), as expected from [11C]flumazenil studies. We found increased tonic inhibitory neurotransmission in our cohort of MRI-negative temporal lobe epilepsy who also had co-morbid memory impairments. Our findings are consistent with a subunit shift from α1/2/3 to α5 in MRI-negative temporal lobe epilepsy.
Corporate Social Responsibility and the Reciprocity Between Employee Perception, Perceived External Prestige, and Employees’ Emotional Labor

Background Corporate social responsibility (CSR) is emerging as a relevant subject in the business world and in the field of management research. Therefore, the current study incorporates classifications often used in organizational level CSR research that distinguish social responsibility relevant to its focus (internal and external), in proposing diverse routes that link various CSR practices (ie, internal and external) to employees’ choice of emotional labor strategy (ie, via perceived organizational support and perceived external prestige). Methods Data were collected from front-line employees of banks operating in Pakistan. Due to the study’s focus on front-line employees, other personnel were excluded for data collection. We collected data through a self-administered questionnaire. The structural equation model (SEM) was employed on 376 valid responses using Smart-PLS3 to test the study hypotheses. Results After the analysis, we found satisfactory results for the fitness of both measurement and satisfactory models. Moreover, the results strongly support our proposed theoretical framework, and all proposed hypotheses were accepted. Discussion This study confirms that the perception of external prestige is a strong predictor of employees’ emotions and relevant behaviors. Moreover, this study discusses under the light of social exchange theory that perceived organizational support strongly predicts employees’ emotional labor, which diminishes the myth that prestige is the only factor to influence employees’ emotions in the workplace. Moreover, this study negates the findings of Anwar et al that perceived external prestige does not have a significant negative effect on surface acting. It provides an insight not only for managers and researchers but also for society, especially in an Eastern workplace setting like Pakistan’s banking sector.
Education of Infectious Diseases Fellows During the COVID-19 Pandemic Crisis: Challenges and Opportunities

Abstract One of the many challenges that has befallen the Infectious Diseases and Graduate Medical Education communities during the coronavirus disease 2019 (COVID-19) pandemic is the maintenance of continued effective education and training of the future leaders of our field. With the remarkable speed and innovation that has characterized the responses to this pandemic, educators everywhere have adapted existing robust and safe learning environments to meet the needs of our learners. This paper will review distinct aspects of education and training of the Infectious Diseases fellows we believe the COVID-19 pandemic has impacted most, including mentoring, didactics, and wellness. We anticipate that several strategies developed in this context and described herein will help to inform training and best practices during the pandemic and beyond.
The Role of Cost in the Integration of Security Features in Integrated Circuits for Smart Cards

This essay investigates the role of cost in the development and production of secure integrated circuits. Initially, I make a small introduction on hardware attacks on smart cards and some of the reasons behind them. Subsequently, I introduce the production phases of chips that are integrated to smart cards and try to identify the costs affecting each one of them. I proceed to identify how adding security features on such integrated circuits may affect the costs of their development and production. I then make a more thorough investigation on the costs of developing a hardware attack for such chips and try to estimate the potential damages and losses of such an attack. I also go on to examine potential ways of reducing the cost of production for secure chips, while identifying the difficulties in adopting them. This essay ends with the conclusion that adding security features to chips meant to be used for secure applications is well worth it, because the costs of developing attacks are of comparable amounts to the costs of developing and producing a chip and the potential damages and losses caused by such attacks can be way higher than these costs. Therefore, although the production and development of integrated circuits come at a certain cost and security introduces further additional costs, security is inherently unavoidable in such chips. Finally, I additionally identify that security is an evolving concept and does not aim to make a chip totally impenetrable, as this may be impossible, but to lower the potential risks, including that of being compromised, to acceptable levels. Thus, a balance needs be found between the level of security and the levels of cost and risk.
Glaucoma as Neurodegeneration in the Brain

Abstract Glaucoma, a group of diseases characterized by progressive optic nerve degeneration that results in irreversible blindness, can be considered a neurodegenerative disorder of both the eye and the brain. Increasing evidence from human and animal studies have shown that glaucoma shares some common neurodegenerative pathways with Alzheimer’s disease (AD) and other tauopathies, such as chronic traumatic encephalopathy (CTE) and frontotemporal dementia. This hypothesis is based on the focal adhesion pathway hypothesis and the spreading hypothesis of tau. Not only has the Apolipoprotein E (APOE) gene been shown to be associated with AD, but also with primary open angle glaucoma (POAG). This review will highlight the relevant literature in the past 20 years from PubMed that show the pathogenic overlap between POAG and AD. Neurodegenerative pathways that contribute to transsynaptic neurodegeneration in AD and other tauopathies might also be similar to those in glaucomatous neurodegeneration.
The use of high-frequency ultrasonography for the diagnosis of palpable nodules after the administration of dermal fillers

Abstract Introduction: Esthetic medicine is a buoyant field of medicine. As the number of performed procedures – mainly injections of botulin toxin and dermal fillers – is increasing, the number of complications is rising as well. The most popular dermal filler is hyaluronic acid. Injection of hyaluronic acid dermal fillers is considered a minimally invasive procedure, but complications in the form of skin nodules and lumps are being encountered more and frequently. Esthetic medicine does not currently offer its own diagnostic methods that would allow one to diagnose complications. In these circumstances, the implementation of objective diagnostic methods from other fields of medicine becomes significant. High-frequency ultrasound is one of such methods. Aim of the study: The aim of this study was to implement high-frequency ultrasound for the diagnosis of palpable nodules after the administration of dermal fillers. Material and method: The study group included 15 women who developed palpable nodules in the region of hyaluronic acid injection. The study includes both early and late complications. An EPIQ 5 (Philips, Bothell, USA) ultrasound machine and a L5–18 transducer were used to examine the nodules. Ultrasound images were evaluated qualitatively by 2 independent investigators. Results: Ultrasound enabled the diagnosis of hyaluronic acid deposition in 9 women, granulomas in 3 women, fibrosis in 2 women and a deposition with inflammation in 1 case. Each of the diagnosed structures presented a typical ultrasound appearance. Conclusions: High-frequency ultrasound is a useful diagnostic method that has a chance to become a widespread tool to diagnose and treat complications. Because of a low number of study reports in this area, continued research is warranted.
Rapid processing of perovskite solar cells in under 2.5 seconds

A rapid annealing technique for CH3NH3PbI3 perovskite solar cells is presented. We report a co-deposited Al2O3–perovskite device annealed in under 2.5 seconds with a PCE of 10.0% compared to 10.9% for a 45 minute oven-annealed device.
Sintering Behaviour and Piezoelectric Properties of CuO-Added Lead-Free Bi(Na,K)TiO3 Ceramics

Effect of excess CuO on the sintering behaviour and piezoelectric properties of Bi0.5(Na82K0.18)0.5TiO3 ceramics was investigated. The addition of small amount of excess CuO as low as 0.01 mol was quite effective to lower the sintering temperature (Ts) of BNKT ceramics down to 975°C which is 200°C lower than the Ts of pure BNKT (1175°C) without significant degradation of their piezoelectric properties. From microstructure analysis, it was concluded that CuO promotes sintering via forming a liquid phase at 975°C and partly dissolves into Ti-sites during sintering.
Comparison of methods for estimation of the covariance matrix of measurement errors

Measurement errors normally present in measured process variables can mask the actual process conditions and lead to wrong operational decisions. This is due not only to the imprecise measured values but also to the propagation of the measurement error through process models used to perform control and optimization tasks. One possible alternative to deal with this problem is to characterize the measurement errors online and to incorporate the obtained information in the process operation. The present work analyzes the performances of different methods used for characterization of measurement errors in different scenarios commonly found in the industrial practice. Based on the obtained results, a method is proposed for direct evaluation of measurement errors at plant site.
Investigation of lipase-catalyzed ring-opening polymerizations of lactones with various ring sizes : kinetic evaluation

Lipase-catalyzed ring-opening polymerizations of lactones with various ring sizes (6- to 13- and the 16-membered ring) employing Novozym 435 demonstrate fascinating differences in their polymerization rates. These differences cannot be related to variations in physical properties such as the dipole moment of the lactones only. For example, 10-decanolactone, 11-undecanolactone, and 12-dodecanolactone show dipole moments of around 1.9 D, but the initial rate constant of their Novozym 435-catalyzed polymerization was found to be 0.10, 0.38, and 4.91 h-1, respectively. The Michaelis−Menten constants KM and Vmax were measured for all lactones, and this revealed that the KM was more or less independent of the ring size, suggesting similar affinities of the lipase for all lactones, while no obvious trend could be discerned for Vmax. However, conformational strain and transannular interactions present in medium ring lactones (ring size 8−12) affect the reactivity of these lactones in lipase catalysis in a similar.
Effect of Case Management on HIV Outcomes for Community Corrections Population: Results of an 18-Month Randomized Controlled Trial

Supplemental Digital Content is Available in the Text. Background: Evidence-based interventions that engage community-dwelling, justice-involved, people living with HIV (PLWH) in care are urgently needed. Project Bridge, an intensive case management intervention, has demonstrated efficacy for linking PLWH to care transitioning from prison to the community. We assessed whether a modified Project Bridge model was effective for increasing rates of HIV treatment engagement, antiretroviral therapy receipt, and adherence for community-dwelling individuals supervised on probation and parole. Setting: Baltimore, Maryland Methods: In this study, the 18-month outcomes of a randomized controlled trial in which PLWH were also on probation or parole received either Project Bridge (n = 50) or treatment as usual (n = 50) were assessed. HIV treatment engagement (primary outcome), antiretroviral therapy prescription, and adherence (secondary outcomes) are evaluated using the intent-to-treat approach. Results: There were no statistically significant differences in rates of HIV treatment engagement, antiretroviral therapy prescription receipt, or adherence between groups over the 18-month study period. Across groups, participants were 5.6 times more likely to receive HIV care, 5.8 times more likely to receive an antiretroviral therapy prescription, and 4 times more likely to report antiretroviral therapy adherence at each follow-up period. Conclusions: Future research is needed to identify potentially less-intensive interventions that target the unique needs of PLWH under community supervision.