Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of Highly Optimized Antibody–Drug Conjugates against CD33 and CD123 for Acute Myeloid Leukemia

Purpose: Mortality due to acute myeloid leukemia (AML) remains high, and the management of relapsed or refractory AML continues to be therapeutically challenging. The reapproval of Mylotarg, an anti-CD33–calicheamicin antibody–drug conjugate (ADC), has provided a proof of concept for an ADC-based therapeutic for AML. Several other ADCs have since entered clinical development of AML, but have met with limited success. We sought to develop a next-generation ADC for AML with a wide therapeutic index (TI) that overcomes the shortcomings of previous generations of ADCs. Experimental Design: We compared the TI of our novel CD33-targeted ADC platform with other currently available CD33-targeted ADCs in preclinical models of AML. Next, using this next-generation ADC platform, we performed a head-to-head comparison of two attractive AML antigens, CD33 and CD123. Results: Our novel ADC platform offered improved safety and TI when compared with certain currently available ADC platforms in preclinical models of AML. Differentiation between the CD33- and CD123-targeted ADCs was observed in safety studies conducted in cynomolgus monkeys. The CD33-targeted ADC produced severe hematologic toxicity, whereas minimal hematologic toxicity was observed with the CD123-targeted ADC at the same doses and exposures. The improved toxicity profile of an ADC targeting CD123 over CD33 was consistent with the more restricted expression of CD123 in normal tissues. Conclusions: We optimized all components of ADC design (i.e., leukemia antigen, antibody, and linker-payload) to develop an ADC that has the potential to translate into an effective new therapy against AML.
Seizure Prediction Using Directed Transfer Function and Convolution Neural Network on Intracranial EEG

Automatic seizure prediction promotes the development of closed-loop treatment system on intractable epilepsy. In this study, by considering the specific information exchange between EEG channels from the perspective of whole brain activities, the convolution neural network (CNN) and the directed transfer function (DTF) were merged to present a novel method for patient-specific seizure prediction. Firstly, the intracranial electroencephalogram (iEEG) signals were segmented and the information flow features of iEEG signals were calculated by using the DTF algorithm. Then, these features were reconstructed as the channel-frequency maps according to channel pairs and the frequency of information flow. Finally, these maps were fed into the CNN model and the outputs were post-processed by the moving average approach to predict the epileptic seizures. By the evaluation of cross-validation method, the proposed algorithm achieved the averaged sensitivity of 90.8%, the averaged false prediction rate of 0.08 per hour. Compared to the random predictor and other existing algorithms tested on the Freiburg EEG dataset, our proposed method achieved better performance for seizure prediction in all patients. These results demonstrated that the proposed algorithm could provide an robust seizure prediction solution by using deep learning to capture the brain network changes of iEEG signals from epileptic patients.
ANME-2d anaerobic methanotrophic archaea differ from other ANME archaea in lipid composition and carbon source

The anaerobic oxidation of methane (AOM) is a microbial process present in marine and freshwater environments. AOM is important for reducing the emission of the second most important greenhouse gas methane. In marine environments anaerobic methanotrophic archaea (ANME) are involved in sulfate-reducing AOM. In contrast, Ca. Methanoperedens of the ANME-2d cluster carries out nitrate AOM in freshwater ecosystems. Despite the importance of those organisms for AOM in non-marine environments not much is known about their lipid composition or carbon sources. To close this gap, we analyzed the lipid composition of ANME-2d archaea and found that they mainly synthesize archaeol and hydroxyarchaeol as well as different (hydroxy-) glycerol dialkyl glycerol tetraethers, albeit in much lower amounts. Abundant lipid headgroups were dihexose, monomethyl-phosphatidyl ethanolamine and phosphatidyl hexose. Moreover, a monopentose was detected as a lipid headgroup which is rare among microorganisms. Batch incubations with 13C labelled bicarbonate and methane showed that methane is the main carbon source of ANME-2d archaea varying from ANME-1 archaea which primarily assimilate dissolved inorganic carbon (DIC). ANME-2d archaea also assimilate DIC, but to a lower extent than methane. The lipid characterization and analysis of the carbon source of Ca. Methanoperedens facilitates distinction between ANME-2d and other ANMEs.
Alterations in the lactate dehydrogenase activity of the desert locust Schistocerca gregaria by the wild plant Fagonia bruguieri (Zygophyllaceae).

The wild plant F. bruguieri extracts caused some alterations in the lactate dehydrogenase activity in haemolymph and fat body of the last instar nymphs and newly emerged adults of the desert locust S. gregaria. Each of two concentration levels of methanolic (7.5 and 3.7%), petroleum ether (30.0 and 15.0%) or n-butanolic extract (30.0 and 15.0%) was applied against the penultimate instar nymphs through the fresh clover leaves, Medicago sativa, as a food. Unexceptionally, all F. bruguieri extracts induced the LDH activity in the haemolymph along the nymphal instar, irrespective of the solvent or concentration level. The strongest inducing effect was exhibited in the mid-aged nymphs (62601.3±467.4 U/L in comparison with 53696.8±467.4 U/L of control congeners) after treatment with the higher concentration level of methanolic extract. On the contrary, the LDH activity was significantly prohibited in the newly emerged adults. The most drastically inhibited enzyme activity was determined (57744.3±467.4 U/L, compared to 62871.2±934.7 U/L of control congeners) after nymphal treatment with higher concentration level of n-butanolic extract. With regard to the fat body, all F. bruguieri extracts prohibited LDH activity along the nymphs instar, irrespective of the concentration level. The most dramatically reduced activity was expressed in (9166.4±119.0 U/L vs. 22839.5±289.1 U/L of control congeners) after treatment with the lower concentration level of nbutanolic extract. In contrast, the plant extracts pronouncedly enhanced the enzyme activity in the fat body of adults, regardless to the extract. The most stimulatory effect was exhibited after treatment of the nymphs with the lower concentration level of nbutanolic extract.
Green Infrastructure Offset the Negative Ecological Effects of Urbanization and Storing Water in the Three Gorges Reservoir Area, China

Land use planning usually increases the uncertainties of the ecosystem structures and functions because various human demands usually bring both positive and negative ecological effects. It is critical for estimating various land use changes and their ecological effects, but the previous studies have failed to decouple the respective and the combined effects of different land use changes on ecosystem services. Net primary productivity (NPP) could be used to indicate many ecosystem services such as carbon sequestration and storage. Here, we employed a light use efficiency model to estimate the spatial and temporal dynamics of NPP in the Three Gorges Reservoir (TGR) area from 2000 to 2015, and designed four scenarios to analyze the relative roles of afforestation, urbanization and storing water on NPP dynamics. Our results documented that terrestrial NPP of the TGR area increased from 547.40 gC•m−2 to 629.96 gC•m−2, and carbon sequestration capacities were 31.66 TgC (1Tg = 1012g) and 36.79 TgC in 2000 and 2015, respectively. Climate change and land use change both could contribute to carbon sequestration with 4.08 TgC and 1.05 TgC. Among these land use changes, only afforestation could sequester carbon with 2.04 TgC, while urbanization-induced and impoundment-induced emissions were 0.12 TgC and 0.32 TgC, respectively, and other land use changes also could release 0.55 TgC of carbon. This finding suggested that although positive and negative environmental effects happened simultaneously over the past decades, green infrastructure could effectively offset the carbon emissions from urbanization and storing water in the TGR area, which provides some fundamental supports for further ecological restoration and contributes to empowering land use policies towards carbon sequestration and storage at the regional scale.
Effects of dopamine on reinforcement learning in Parkinson’s disease depend on motor phenotype

See Manohar (doi:10.1093/brain/awaa363) for a scientific commentary on this article. Parkinson’s disease is complicated by great variability in symptoms. Van Nuland et al. report that the well-established effects of levodopa on reinforcement learning apply only to patients without tremor symptoms, suggesting a need to revisit neurocognitive models of dopaminergic function in Parkinson’s disease.
Patterns of RNA Editing in Newcastle Disease Virus Infections

The expression of accessory non-structural proteins V and W in Newcastle disease virus (NDV) infections depends on RNA editing. These proteins are derived from frameshifts of the sequence coding for the P protein via co-transcriptional insertion of one or two guanines in the mRNA. However, a larger number of guanines can be inserted with lower frequencies. We analysed data from deep RNA sequencing of samples from in vitro and in vivo NDV infections to uncover the patterns of mRNA editing in NDV. The distribution of insertions is well described by a simple Markov model of polymerase stuttering, providing strong quantitative confirmation of the molecular process hypothesised by Kolakofsky and collaborators three decades ago. Our results suggest that the probability that the NDV polymerase would stutter is about 0.45 initially, and 0.3 for further subsequent insertions. The latter probability is approximately independent of the number of previous insertions, the host cell, and viral strain. However, in LaSota infections, we also observe deviations from the predicted V/W ratio of about 3:1 according to this model, which could be attributed to deviations from this stuttering model or to further mechanisms downregulating the abundance of W protein.
Regulation of the regenerative activity of dental pulp stem cells from exfoliated deciduous teeth (SHED) of children by TGF-β1 is associated with ALK5/Smad2, TAK1, p38 and MEK/ERK signaling

Transforming growth factor-β1 (TGF-β1) regulates wound healing/regeneration and aging processes. Dental pulp stem cells from human exfoliated deciduous teeth (SHED) are cell sources for treatment of age-related disorders. We studied the effect of TGF-β1 on SHED and related signaling. SHED were treated with TGF-β1 with/without pretreatment/co-incubation by SB431542, U0126, 5Z-7-oxozeaenol or SB203580. Sircol collagen assay, 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) assay, alkaline phosphatase (ALP) assay, RT-PCR, western blotting and PathScan phospho-ELISA were used to measure the effects. We found that SHED expressed ALK1, ALK3, ALK5, TGF-RII, betaglycan and endoglin mRNA. TGF-β1 stimulated p-Smad2, p-TAK1, p-ERK, p-p38 and cyclooxygenase-2 (COX-2) protein expression. It enhanced proliferation and collagen content of SHED that were attenuated by SB431542, 5Z-7-oxozeaenol and SB203580, but not U0126. TGF-β1 (0.5-1 ng/ml) stimulated ALP of SHED, whereas 5-10 ng/ml TGF-β1 suppressed ALP. SB431542 reversed the effects of TGF-β1. However, 5Z-7-oxozeaenol, SB203580 and U0126 only reversed the stimulatory effect of TGF-β1 on ALP. Four inhibitors attenuated TGF-β1-induced COX-2 expression. TGF-β1-stimulated TIMP-1 and N-cadherin was inhibited by SB431542 and 5Z-7-oxozeaenol. These results indicate that TGF-β1 affects SHED by differential regulation of ALK5/Smad2/3, TAK1, p38 and MEK/ERK. TGF-β1 and SHED could potentially be used for tissue engineering/regeneration and treatment of age-related diseases.
Unstructured Socializing with Peers, Low Self-Control, and Substance Use

Research consistently finds that unstructured socializing with peers and low self-control are both positively associated with substance use among adolescents. However, largely absent from the literature is a consideration of whether unstructured socializing with peers and low self-control have differential and interactive effects when predicting usage of different classifications of drugs. The current study addresses these issues using data collected on a statewide sample of middle school and high school students who participated in the 2017 Florida Youth Substance Abuse Survey. Results indicate that (1) unstructured socializing with peers is a stronger predictor of soft drug use than low self-control, (2) low self-control is a stronger predictor of hard drug use than unstructured socializing with peers, and (3) the effect of unstructured socializing on both soft and hard drug use is diminished among adolescents who are lower in self-control.
Identification of prognostic immune genes in laryngeal cancer

Objective In this study, we aimed to identify prognostic immune-related genes and establish a prognostic model for laryngeal cancer based on these genes. Methods Transcriptome profiles and clinical data of patients with laryngeal cancer were downloaded from The Cancer Genome Atlas database. Integrated bioinformatics analyses were performed to identify genes associated with prognosis. Results Thirty prognostic immune-related genes for laryngeal cancer were identified. We constructed a regulatory network of prognosis comprising transcription factors and immune-related genes. Multivariate Cox regression analyses identified 15 immune-related genes in the network that were used to establish the prognostic model. The model exhibited excellent prognostic prediction ability with a high area under the curve value (0.916). The calculated risk score based on expression of the 15 immune-related genes was shown to be an independent prognostic factor for laryngeal cancer. Conclusion We identified prognostic immune-related genes and established a prognostic model for laryngeal cancer, which might help identify novel predictive biomarkers and therapeutic targets of laryngeal cancer.
PHYSICO-MECHANICAL PROPERTIES AND DIMENSIONAL STABILITY OF NATURAL FIBRE COMPOSITES FABRICATED FROM POLYETHYLENE WASTE AND WALNUT SHELLS

Within the framework of the study, a series of composites were produced with different shares of finely ground walnut shells (10%, 25% and 40% mass). Polyethylene obtained from selective packaging waste collection was used as a matrix, and the preparation process was in two stages – mixed and injection. The produced materials were analyzed for their physical properties (density, moisture content), mechanical properties (hardness, Young’s modulus, DMA), and resistance to environmental factors (swelling and water absorption, TGA). The particle size distribution of the filler and morphological properties of the composites (SEM) was also investigated. The addition of the plant filler increases the hardness and considerably improves the stiffness of the composite. The absorptivity of the described NFCs is comparable to that of natural-filled composites containing additives that slow down the swelling process.
An Estimation of the Impact of Financial Intermediation on the Economic Growth of Ghana; With Emphasis on the Private Sector

DOI: http://dx.doi. org/10.24018/ejbmr.2020. 5.5. 529 Vol 5 | Issue 5 | October 2020 1 Abstract — It is an undeniable and acceptable fact that all economic agents namely; individuals, corporations and governments require money to meet their specific needs which may differ from one economic agent to another. The monetary activities of these economic agents which have to be financed by someone else exert an overall effect on the entire economy. The challenge here, therefore, is about the availability of banks’ credit and its allocation to the various economic agents as well as the economic results they deliver to Ghana’s economy. Thus, the basic issue which the study sought to dwell on is ‘how commercial banks’ credit allocated to the private sector impacts on the growth of the entire economy of Ghana’. The study conducted is exploratory in nature and the approach was purely quantitative making use of secondary data relating to financial intermediation and economic growth spanning from 1993 to 2018. Purposive sampling technique was used in selecting data and its source. To estimate the parameters in the econometric model stated in the study using times series data, AutoRegressive Distributive Lag (ARDL) bounds testing approach to co-integration developed by Pesaran et al. was employed. Overall, the empirical evidence obtained indicates that there is a negative long-run relationship between domestic banks credit to the private sector and Ghana’s economic growth, though statistically insignificant at 5% significance level. In the shortrun however, the negative relationship between the two variables is statistically significant at the same significance level.
Effectiveness of Continuous Positive Airway Pressure Versus Mandibular Advancement Device in Severe Obstructive Sleep Apnea Patients With Mandibular Retrognathia: A Prospective Clinical Trial

Aim: Some obstructive sleep apnea (OSA) patients may have mandibular retrognathia (ANB > 4.7° and SNB < 76.2°). Currently, there are no studies that have compared the effectiveness of continuous positive airway pressure (CPAP) versus mandibular advancement device (MAD) in severe OSA patients with mandibular retrognathia. We explored the efficacy of CPAP versus MAD for the treatment of severe OSA patients with mandibular retrognathia. Methods: A total of 105 patients were enrolled. Outcomes were assessed by using polysomnography, Epworth Sleepiness Scale (ESS), Snore Scale (SS), Self-rating Anxiety Scale (SAS), and compliance, before treatment and after 6 and 12 months of treatment. Results: Continuous positive airway pressure was superior to MAD in improving polysomnographic outcomes and SS score, but reported compliance was higher on MAD. There is no significant difference between the 2 treatments in terms of ESS score and SAS score. Obstructive sleep apnea patients with mandibular retrognathia showed greater improvement than those without mandibular retrognathia in terms of apnea-hypopnea index and oxygen desaturation index after MAD. Conclusion: Continuous positive airway pressure and MAD are both effective in treating severe OSA patients with mandibular retrognathia. Mandibular advancement device is a good alternative to CPAP in severe OSA patients with mandibular retrognathia. Mandibular advancement device is more effective in treating OSA patients with mandibular retrognathia than those without. Trial registration: ChiCTR2000032541.
Oral Testofen, L-Citrulline, Resveratrol, and Caffeine Supplement Drink Improves Sexual Function in Men with Phosphodiesterase 5 Inhibitors: Randomized, Double-Blind, Placebo-Controlled Crossover Pilot Study

Purpose Sexuality is very important for men's health. Currently, phosphodiesterase type 5 inhibitors (PDE5i) remain the first-line therapy for erectile dysfunction, and no other oral drugs or drinks are approved and used clinically to treat male libido or orgasm dysfunction. In reference to a pharmaceutical dosage document, growing health consciousness is said to have boosted yearly sales of supplement drinks to more than 170 billion yen (1.58 billion US dollars) in Japan. We have created a supplement drink comprised of testofen, L-citrulline, resveratrol, and caffeine. We hypothesized that our supplement drink would be effective for men with sexual dysfunction, and especially libido dysfunction. Materials and Methods In this study, men with sexual dysfunction received a placebo drink for 14 days or our supplement drink (testofen, 600 mg/d; L-citrulline, 800 mg/d; resveratrol, 300 mg/d; and caffeine, 40 mg/d) for another 14 days separated by a 7-day washout period. Patients continued on-demand use of PDE5i. The International Index of Erectile Function (IIEF) score and adverse events were assessed. Results Twenty patients aged 30–7 years old were enrolled in and concluded the study with no adverse events experienced. The IIEF domains of desire frequency, erection frequency, erection firmness, erection confidence, intercourse satisfaction, ejaculation frequency, orgasm frequency, and overall satisfaction were significantly improved with our supplement drink. Conclusions This is the first study to show that our supplement drink may not only be effective for erection but also for libido, orgasm, and ejaculation.
SEIPIN: A Key Factor for Nuclear Lipid Droplet Generation and Lipid Homeostasis

Lipid homeostasis is essential for normal cell physiology. Generally, lipids are stored in a lipid droplet (LD), a ubiquitous organelle consisting of a neutral lipid core and a single layer of phospholipid membrane. It is thought that LDs are generated from the endoplasmic reticulum and then released into the cytosol. Recent studies indicate that LDs can exist in the nucleus, where they play an important role in the maintenance of cell phospholipid homeostasis. However, the details of nuclear lipid droplet (nLD) generation have not yet been clearly characterized. SEIPIN is a nonenzymatic protein encoded by the Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) gene. It is associated with lipodystrophy diseases. Many recent studies have indicated that SEIPIN is essential for LDs generation. Here, we review much of this research in an attempt to explain the role of SEIPIN in nLD generation. From an integrative perspective, we conclude by proposing a theoretical model to explain how SEIPIN might participate in maintaining homeostasis of lipid metabolism.
Are you really doing ‘codesign’? Critical reflections when working with vulnerable populations

‘Codesign’ and associated terms such as ‘coproduction’ or ‘patient engagement’, are increasingly common in the health research literature, due to an increased emphasis on the importance of ensuring that research related to service/systems development is meaningful to end-users. However, there continues to be a lack of clarity regarding the key principles and practices of codesign, and wide variation in the extent to which service users are meaningfully engaged in the process. These issues are particularly acute when end-users include populations who have significant health and healthcare disparities that are linked to a range of intersecting vulnerabilities (eg, poverty, language barriers, age, disability, minority status, stigmatised conditions). The purpose of this paper is to prompt critical reflection on the nature of codesign research with vulnerable populations, including key issues to consider in the initial planning phases, the implementation process, and final outputs. Risks and tensions will be identified in each phase of the process, followed by a tool to foster reflexivity in codesign processes to address these issues.