Miracle-dz/UniFAR-FTUs huggingface dataset:
Machine-Learning-Assisted De Novo Design of Organic Molecules and Polymers: Opportunities and Challenges

Organic molecules and polymers have a broad range of applications in biomedical, chemical, and materials science fields. Traditional design approaches for organic molecules and polymers are mainly experimentally-driven, guided by experience, intuition, and conceptual insights. Though they have been successfully applied to discover many important materials, these methods are facing significant challenges due to the tremendous demand of new materials and vast design space of organic molecules and polymers. Accelerated and inverse materials design is an ideal solution to these challenges. With advancements in high-throughput computation, artificial intelligence (especially machining learning, ML), and the growth of materials databases, ML-assisted materials design is emerging as a promising tool to flourish breakthroughs in many areas of materials science and engineering. To date, using ML-assisted approaches, the quantitative structure property/activity relation for material property prediction can be established more accurately and efficiently. In addition, materials design can be revolutionized and accelerated much faster than ever, through ML-enabled molecular generation and inverse molecular design. In this perspective, we review the recent progresses in ML-guided design of organic molecules and polymers, highlight several successful examples, and examine future opportunities in biomedical, chemical, and materials science fields. We further discuss the relevant challenges to solve in order to fully realize the potential of ML-assisted materials design for organic molecules and polymers. In particular, this study summarizes publicly available materials databases, feature representations for organic molecules, open-source tools for feature generation, methods for molecular generation, and ML models for prediction of material properties, which serve as a tutorial for researchers who have little experience with ML before and want to apply ML for various applications. Last but not least, it draws insights into the current limitations of ML-guided design of organic molecules and polymers. We anticipate that ML-assisted materials design for organic molecules and polymers will be the driving force in the near future, to meet the tremendous demand of new materials with tailored properties in different fields.
Structural and Biophysical Analyses of Human N-Myc Downstream-Regulated Gene 3 (NDRG3) Protein

The N-Myc downstream-regulated gene (NDRG) family belongs to the α/β-hydrolase fold and is known to exert various physiologic functions in cell proliferation, differentiation, and hypoxia-induced cancer metabolism. In particular, NDRG3 is closely related to proliferation and migration of prostate cancer cells, and recent studies reported its implication in lactate-triggered hypoxia responses or tumorigenesis. However, the underlying mechanism for the functions of NDRG3 remains unclear. Here, we report the crystal structure of human NDRG3 at 2.2 Å resolution, with six molecules in an asymmetric unit. While NDRG3 adopts the α/β-hydrolase fold, complete substitution of the canonical catalytic triad residues to non-reactive residues and steric hindrance around the pseudo-active site seem to disable the α/β-hydrolase activity. While NDRG3 shares a high similarity to NDRG2 in terms of amino acid sequence and structure, NDRG3 exhibited remarkable structural differences in a flexible loop corresponding to helix α6 of NDRG2 that is responsible for tumor suppression. Thus, this flexible loop region seems to play a distinct role in oncogenic progression induced by NDRG3. Collectively, our studies could provide structural and biophysical insights into the molecular characteristics of NDRG3.
Time for Epinephrine Reboot or Give It the Boot: What Is Learned From This Meta-Analysis.

266 www.ccmjournal. org February 2020 • Volume 48 • Number 2 8. Colman E, Yin EB, Laine G, et al: Evaluation of a heparin monitoring protocol for extracorporeal membrane oxygenation and review of the literature. J Thorac Dis 2019; 11:3325–3335 9. Mazzeffi M, Greenwood J, Tanaka K, et al: Bleeding, transfusion, and mortality on extracorporeal life support: ECLS Working Group on thrombosis and hemostasis. Ann Thorac Surg 2016; 101:682–689 10. Lockie CJA, Gillon SA, Barrett NA, et al: Severe respiratory failure, extracorporeal membrane oxygenation, and intracranial hemorrhage. Crit Care Med 2017; 45:1642–1649 11. Cooper E, Burns J, Retter A, et al: Prevalence of venous thrombosis following venovenous extracorporeal membrane oxygenation in patients with severe respiratory failure. Crit Care Med 2015; 43:e581–e584 12. Rehder KJ, Turner DA, Hartwig MG, et al: Active rehabilitation during extracorporeal membrane oxygenation as a bridge to lung transplantation. Respir Care 2013; 58:1291–1298 13. Parzy G, Daviet F, Persico N, et al: Prevalence and Risk Factors for Thrombotic Complications Following Venovenous Extracorporeal Membrane Oxygenation: A CT Scan Study. Crit Care Med 2020; 48:192–199 14. Menaker J, Tabatabai A, Rector R, et al: incidence of cannula-associated deep vein thrombosis after veno-venous extracorporeal membrane oxygenation. ASAIO J 2017; 63:588–591 15. Ontaneda A, Annich GM: Novel surfaces in extracorporeal membrane oxygenation circuits. Front Med (Lausanne) 2018; 5:321
Synthesis and Thermal Investigations of Eleven-Membered Ring Systems Containing One of the Heavier Group 14 Element Atoms Si, Ge, and Sn

Unique eleven-membered rings containing silicon, germanium, and tin were synthesized in good yields by the reactions of the corresponding 1,2-bis((2-bromothiophen-3-yl)methoxy)benzenes with (C6H5)2ECl2 where E = Sn, Ge, Si. The Sn and Ge congeners were crystallized, but the conformers that these rings crystallized in, were quite different. As confirmed by Density Functional Theory (DFT) calculations, (C28H22O2S2Sn) assumes a unique crystal structure that leaves more room around the tetrel atom as compared to the crystal structure of the corresponding Ge compound. In the latter, the central cavity is quite open, whereas in the former, one of the methylene groups can fold inwards. Another consequence is the influence on the planes of the aromatic rings flanking the heterocycle. In the Ge case, the benzene ring is folded away from the central cavity, whereas in the Sn case, it is almost parallel to the imaginary axis through the center of the ring. Thermal analysis investigations (TGA and DSC methods) of these eleven-membered rings suggested the loss of a phenyl group in the first decomposition step. The decomposition temperature decreased from the Si containing heterocycle to Ge and was lowest for the Sn containing heterocycle.
Prevalence, Prevention and Treatment of Saddle Sores among Female Competitive Cyclists: A Scoping Review Protocol

Female cyclists are prone to a variety of injuries and illnesses that occur as a result of prolonged contact with a bicycle saddle. Saddle sores are a range of skin ailments on the buttocks, genitals and inner thigh that result from a combination of friction, heat, pressure, moisture and bacteria in the saddle area. Whilst saddle sores are reportedly common, for some cyclists, the condition may cause only mild discomfort. However, for female competitive cyclists, the condition can be an ongoing source of pain and illness affecting participation and performance in the sport. Despite many online sources for health information and products for saddle sores, it is unknown what empirical evidence exists for the prevalence and severity of saddle sores, and for the effectiveness of prevention and treatment methods. This paper outlines the protocol for a scoping review, which aims to describe the empirical evidence for the prevalence, prevention and treatment of saddle sores among female competitive cyclists. Ethics approval has been obtained for this study from Curtin University’s Human Research Ethics Committee no: HRE2019-0120. The findings from this study will contribute to the literature for injury in female sport.
Molecular Detection of Gamma Coronaviruses in Bird Parks of Iran.

Gamma Coronaviruses (GCoVs) are distributed worldwide, affecting a wide range of bird species, the beluga whale, and bottlenose dolphins. Because of the limited proofreading capability in the viral encoded polymerase, they emerge genetically diverse. There has been no molecular surveillance data to describe the epidemiology of GCOVs in avian species. The present study was conducted to detect GCOVs in Tehran birds’ parks, 2015. Cloacal swabs (267 samples) from eight different bird species ((Chickens (Gallus gallus), Pheasant (Phasianus colchicus), Turkey (Meleagris gallopavo), Partridge (Perdix perdix), Quail (Coturnix coturnix), Duck (Anas platyrhynchos), Goose (Anserini),and Guinea fowl (Numididae)) were collected, the viral RNA was extracted, the RT-PCR was performed using QIAGEN one step RT-PCR kit and the primers targeting “3'-UTR” and “Nucleocapsid” genes. The detection rate was approximately 8.99%. GCOVs were detected in the chicken, quail, pheasant, turkey, and the partridge with different prevalence rates. Phylogenetic tree based on partial nucleotide sequences of the N gene clustered the samples into two groups. It is the first report of GCOVs in non-commercial birds in Iran. According to our results, GCOVs are circulating in different avian species, and further studies are needed to isolate these viruses and evaluate their pathogenesis.
In Vitro, In Vivo, and In Silico Methods for Assessment of Muscle Size and Muscle Growth Regulation

ABSTRACT Trauma, burn injury, sepsis, and ischemia lead to acute and chronic loss of skeletal muscle mass and function. Healthy muscle is essential for eating, posture, respiration, reproduction, and mobility, as well as for appropriate function of the senses including taste, vision, and hearing. Beyond providing support and contraction, skeletal muscle also exerts essential roles in temperature regulation, metabolism, and overall health. As the primary reservoir for amino acids, skeletal muscle regulates whole-body protein and glucose metabolism by providing substrate for protein synthesis and supporting hepatic gluconeogenesis during illness and starvation. Overall, greater muscle mass is linked to greater insulin sensitivity and glucose disposal, strength, power, and longevity. In contrast, low muscle mass correlates with dysmetabolism, dysmobility, and poor survival. Muscle mass is highly plastic, appropriate to its role as reservoir, and subject to striking genetic control. Defining mechanisms of muscle growth regulation holds significant promise to find interventions that promote health and diminish morbidity and mortality after trauma, sepsis, inflammation, and other systemic insults. In this invited review, we summarize techniques and methods to assess and manipulate muscle size and muscle mass in experimental systems, including cell culture and rodent models. These approaches have utility for studies of myopenia, sarcopenia, cachexia, and acute muscle growth or atrophy in the setting of health or injury.
Cluster of specified microRNAs in tissues and serum as biomarkers for early diagnosis of hepatocellular carcinoma.

OBJECTIVE Hepatocellular carcinoma (HCC) is a global public health concern that lacks efficient methods for early diagnosis. Accumulated evidence has revealed great potential using microRNAs (miRNAs) as noninvasive biomarkers in HCC detection. METHODS Serum miRNAs (miR21, miR122, miR-214, miR15b, and let-7f) were detected in 75 patients with HCC and 80 healthy controls (HC). In addition, 75 HCC tissues and paired normal adjacent tissues were also analyzed for comparison. Quantified by real-time quantitative RT-PCR was used to evaluate the expression of miRNAs. RESULTS We discovered significant up-regulation of miR-21 (P < 0.001) and miR-15b (P < 0.001) as well as a down-regulation of miR-122 (P = 0.01) in HCC tissues compared to adjacent non-tumor tissues. Additionally, miR-21 (P < 0.001) and miR-15b (P < 0.001) levels were upregulated in serum and miR-214 (P = 0.01) was decreased in HCC patients compared to that in healthy controls. Multivariate logistic regression analysis showed that serum miR-21 (OR = 1.68, P = 0.012) and miR-15b (OR = 1.736, P = 0.012) were independently associated with HCC whereas miR-214 (OR = 0.631, P = 0.006) was associated with a decreased risk of HCC. When we employed miR-(21 + 122 + 15b) classifier as biomarkers, we could discriminate HCC tissues from adjacent non-tumor tissues with an AUC of 0.885 (specificity: 89.7%; sensitivity: 73.1%). In serum, the cluster of miR-(21 + 214 + 15b) classifier (AUC = 0.887) had a sensitivity of 80.3% and a specificity of 87.0% for HCC diagnosis. CONCLUSION Our results suggest that these serum miRNAs may be useful markers for discriminating HCC patients from healthy controls. Combined determination of circulating miR-21, miR-122, miR-214, and miR-15b has great potential to serve as an accurate and noninvasive biomarker for the early HCC preliminary screening.
Capsular glycan recognition provides antibody-mediated immunity against tuberculosis.

A better understanding of all immune components involved in protecting against M. tuberculosis infection is urgently needed to inform strategies for novel immunotherapy and tuberculosis (TB) vaccine development. While cell-mediated immunity is critical, increasing evidence supports that antibodies also have a protective role against TB. Yet, knowledge of protective antigens is limited. Analyzing sera from 97 US immigrants at various states of M. tuberculosis infection, we showed protective in vitro and in vivo efficacy of polyclonal IgG to the M. tuberculosis capsular polysaccharide arabinomannan (AM). Using recently developed glycan arrays, we established that anti-AM IgG induced in natural infection is highly heterogeneous in its binding specificity and differs in both its reactivity to oligosaccharide motifs within AM and its functions between BCG vaccination and/or controlled (latent) versus uncontrolled (TB) M. tuberculosis infection. We showed that anti-AM IgG from asymptomatic but not diseased individuals was protective, and provided data suggesting a potential role of IgG2 and specific AM oligosaccharides. Filling a gap in the current knowledge of protective antigens in humans, our data support the key role of the M. tuberculosis surface glycan AM and suggest the importance of targeting specific glycan epitopes within AM in antibody-mediated immunity against TB.
Association between clinical risk factors and severity of dysphagia after extubation based on a videofluoroscopic swallowing study

Background/Aims This study aimed to evaluate the correlation between clinical risk factors of post-extubation dysphagia (PED) and the severity of impaired pharyngeal swallowing function assessed via videofluoroscopic swallowing studies (VFSSs). Methods This study was a retrospective review of medical records. Of 116 patients who were admitted to the intensive care unit and underwent VFSS, 32 who had non-neurologic disorders and experienced prolonged intubation (for more than 48 hours) were diagnosed with PED. The severity of PED was evaluated by using a functional dysphagia scale (FDS) and a penetration aspiration scale (PAS), on the basis of VFSS. Results The Simplified Acute Physiology Score 3 and total FDS score were positively correlated (r = 0.40, p = 0.02). Intubation duration was positively correlated with total PAS and FDS scores (r = 0.62, p < 0.001; r = 0.65, p < 0.001, respectively). The amounts of residue in the valleculae (RV) and pyriform sinuses (RP) were associated with intubation duration (r = 0.58, p < 0.001; r = 0.57, p < 0.001, respectively). Multivariate regression analysis revealed that intubation duration was significantly associated with the total FDS score, RV and RP subscales of the FDS, and total PAS score. Conclusions The severity of impaired swallowing function, particularly the amount of residue in the pharyngeal recesses assessed via VFSS, was strongly associated with both severity of medical illness and intubation duration. Intubation duration could be a prognostic factor for assessing impaired swallowing function on the basis of VFSS.
Cyclic AMP Regulates Key Features of Macrophages via PKA: Recruitment, Reprogramming and Efferocytosis

Macrophages are central to inflammation resolution, an active process aimed at restoring tissue homeostasis following an inflammatory response. Here, the effects of db-cAMP on macrophage phenotype and function were investigated. Injection of db-cAMP into the pleural cavity of mice induced monocytes recruitment in a manner dependent on PKA and CCR2/CCL2 pathways. Furthermore, db-cAMP promoted reprogramming of bone-marrow-derived macrophages to a M2 phenotype as seen by increased Arg-1/CD206/Ym-1 expression and IL-10 levels (M2 markers). Db-cAMP also showed a synergistic effect with IL-4 in inducing STAT-3 phosphorylation and Arg-1 expression. Importantly, db-cAMP prevented IFN-γ/LPS-induced macrophage polarization to M1-like as shown by increased Arg-1 associated to lower levels of M1 cytokines (TNF-α/IL-6) and p-STAT1. In vivo, db-cAMP reduced the number of M1 macrophages induced by LPS injection without changes in M2 and Mres numbers. Moreover, db-cAMP enhanced efferocytosis of apoptotic neutrophils in a PKA-dependent manner and increased the expression of Annexin A1 and CD36, two molecules associated with efferocytosis. Finally, inhibition of endogenous PKA during LPS-induced pleurisy impaired the physiological resolution of inflammation. Taken together, the results suggest that cAMP is involved in the major functions of macrophages, such as nonphlogistic recruitment, reprogramming and efferocytosis, all key processes for inflammation resolution.
Development of a Mycoinsecticide Bait Formulation for the Control of House Flies, Musca domestica L.

The control of house flies, Musca domestica (L.), currently relies on the use of chemical insecticide spray and bait formulations. Entomopathogenic fungi, such as Metarhizium anisopliae, may provide an alternative to these products. This study aimed to develop and evaluate a mycoinsecticide bait formulation containing a virulent M. anisopliae isolate. Five M. anisopliae isolates were screened against M. domestica and isolate M16 was selected for bait development. Bait formulations containing a variety of additives, including (Z)-9-tricosene, were tested for their ability to increase fly visitation. A bait formulation containing M. anisopliae and skim milk powder was found to have the highest house fly visitation and was subsequently compared to a conventional chemical bait in an efficacy assay. The chemical bait (0.5% imidacloprid) caused faster mortality than the mycoinsecticide bait, however, similar levels of mortality were achieved by 4–5 days’ post exposure. These results suggest that M. anisopliae mycoinsecticide baits may offer an alternative to conventional chemical insecticides for the control of house flies in suitable areas.
Association of Total Flavonoid Intake with Hypo-HDL-Cholesterolemia among Korean Adults: Effect Modification by Polyunsaturated Fatty Acid Intake

The aim of this study was to examine the independent association between flavonoid intake and hypo-high-density lipoprotein (HDL)-cholesterolemia and the potential modifying effect of polyunsaturated fatty acid (PUFA) intake on this association among Korean adults. This cross-sectional analysis used data from 10,326 subjects who participated in the 2013–2016 Korean National Health and Nutrition Examination Survey. Multiple logistic regression analyses were used to assess the associations of flavonoid and PUFA intakes with hypo-HDL-cholesterolemia prevalence. Proanthocyanidins intake showed an inverse relationship with hypo-HDL-cholesterolemia only in men (Tertile (T) 3 vs. T1: odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.59–0.92, p-trend = 0.0330). Total flavonoid and PUFA intakes were not associated with hypo-HDL-cholesterolemia in both men and women. However, when stratified by PUFA intake, there was an inverse relationship between total flavonoid intake and hypo-HDL-cholesterolemia prevalence in men with a high n-3 PUFA intake (total flavonoid intakes T3 vs. T1: OR = 0.59, 95% CI = 0.42–0.82, p-trend = 0.0004) or a low n-6/n-3 PUFA intake ratio (T3 vs. T1: OR = 0.67, 95% CI = 0.48–0.93, p-trend = 0.0053), but not in those with a low n-3 PUFA intake (p-interaction = 0.0038) or a high n-6/n-3 PUFA intake ratio (p-interaction = 0.1772). In women, no association was found between total flavonoid intake and hypo-HDL-cholesterolemia, regardless of PUFA intake. These results imply that the intake of proanthocyanidins might have beneficial effects on the HDL-cholesterol level in Korean men. In addition, n-3 PUFA intake might modify the association of total flavonoid intake with the hypo-HDL-cholesterolemia among Korean men.
Multi-Terminal Transistor-Like Devices Based on Strongly Correlated Metallic Oxides for Neuromorphic Applications

Memristive devices are attracting a great attention for memory, logic, neural networks, and sensing applications due to their simple structure, high density integration, low-power consumption, and fast operation. In particular, multi-terminal structures controlled by active gates, able to process and manipulate information in parallel, would certainly provide novel concepts for neuromorphic systems. In this way, transistor-based synaptic devices may be designed, where the synaptic weight in the postsynaptic membrane is encoded in a source-drain channel and modified by presynaptic terminals (gates). In this work, we show the potential of reversible field-induced metal-insulator transition (MIT) in strongly correlated metallic oxides for the design of robust and flexible multi-terminal memristive transistor-like devices. We have studied different structures patterned on YBa2Cu3O7−δ films, which are able to display gate modulable non-volatile volume MIT, driven by field-induced oxygen diffusion within the system. The key advantage of these materials is the possibility to homogeneously tune the oxygen diffusion not only in a confined filament or interface, as observed in widely explored binary and complex oxides, but also in the whole material volume. Another important advantage of correlated oxides with respect to devices based on conducting filaments is the significant reduction of cycle-to-cycle and device-to-device variations. In this work, we show several device configurations in which the lateral conduction between a drain-source channel (synaptic weight) is effectively controlled by active gate-tunable volume resistance changes, thus providing the basis for the design of robust and flexible transistor-based artificial synapses.