Miracle-dz/UniFAR-FTUs huggingface dataset:
Turning sugar into oil: making photosynthesis blind to feedback inhibition

This article comments on: Beechey-Gradwell Z, Cooney L, Winichayakul S, Andrews M, Hea SY, Crowther T, Roberts N. 2020. Storing carbon in leaf lipid sinks enhanced perennial ryegrass carbon capture especially under high N and elevated CO2. Journal of Experimental Botany 71, 2351–2361.
Improving Protein-Peptide Docking Results via Pose-Clustering and Rescoring with a Combined Knowledge-Based and MM-GBSA Scoring Function

Protein-peptide docking, which predicts the complex structure between a protein and a peptide, is a valuable computational tool in peptide therapeutics development and mechanistic investigation of peptides involved cellular processes. Although current peptide docking approaches are often able to sample near-native peptide binding modes, correctly identifying those near-native modes from decoys is still challenging due to the extremely high complexity of peptide binding energy landscape. In this study, we have developed an efficient post-docking rescoring protocol using a combined scoring function of knowledge-based ITScorePP potentials and physics- based MM-GBSA energies. Tested on five benchmark/docking test sets, our post-docking strategy showed an overall significantly better performance in binding mode prediction and score-RMSD correlation than original docking approaches. Specifically, our post-docking protocol outperformed original docking approaches with the success rates of 15.8% vs. 10.5% for pepATTRACT on the Global 57 benchmark, 5.3% vs. 5.3% for CABS-dock on the Global 57 benchmark, 17.0% vs. 11.3% for FlexPepDock on the LEADS-PEP data set, 40.3% vs. 33.9% for HPEPDOCK on the Local 62 benchmark, and 64.2% vs. 52.8% for HPEPDOCK on the LEADS-PEP data set when the top prediction was considered. There results demonstrated the efficacy and robustness of our post-docking protocol.
Should chloroquine and hydroxychloroquine be used to treat COVID-19? A rapid review

Background On the 11 March 2020, the World Health Organization (WHO) declared that COVID-19 was a pandemic. To date, there are no medical treatments for COVID-19 with proven effectiveness. Novel treatments and/or vaccines will take time to be developed and distributed to patients. In light of this, there has been growing interest in the use of existing medications, such as chloroquine (CQ) and hydroxychloroquine (HCQ), as potential treatments of this disease. Aim To establish the current evidence for the effectiveness of CQ and HCQ in treating COVID-19. Design & setting A rapid review of the literature was conducted. Method Electronic searches in PubMed and Google Scholar were conducted on 21 March 2020. A further search was conducted in Google for relevant literature on 28 March 2020. Results There is limited evidence of in vitro activity of CQ/HCQ against SARS-CoV-2. A number of in vivo clinical trials are underway. The empirical data available from two of these trials reveal conflicting results. Both trials are characterised by small numbers of participants (n = 30 and n = 36) and suffer methodological limitations. No medium or long-term follow-up data is available. Conclusion At present, there is insufficient evidence to determine whether CQ/HCQ are safe and effective treatments for COVID-19. High quality, adequately powered randomised clinical trials in primary and secondary care settings are urgently required to guide policymakers and clinicians. These studies should report medium- and long-term follow-up results, and safety data.
Association of Peripheral Blood RASSF1A and CDKN2A Methylation Status with Smoking Behaviour in Nasopharyngeal Carcinoma

BACKGROUND: Hypermethylation of RASSF1A and CDKN2A is one of epigenetic factor underlies nasopharyngeal carcinoma (NPC) development. Smoking behavior as an NPC’s risk factor causes aberrant DNA methylation. RASSF1A and CDKN2A promoter hypermethylation from peripheral blood cells correlates with smoking behavior. The use of body fluids including peripheral blood as a specimen for DNA methylation analyzes are widely developed, as less invasive method compared to the use of tissue biopsy. This study aims to observe the association between RASSF1A and CDKN2A methylation in peripheral blood and smoking behavioramong NPC patients.METHODS: Newly diagnosed NPC subjects were recruited from ear-nose-throat (ENT) outpatient clinic of Dr. Sardjito Hospital, Yogyakarta. DNA from buffycoat of 19 smokers and 20 non-smokers NPC’s patients were isolated. Bisulphite modification was applied to 500 ng of the isolated DNA. The methylation status was detected by MSP (methylation-specific polymerase chain reaction (PCR)). The association between smoking status and promoter hypermethylation was analysis using Chi-Square test.RESULTS: MSP analysis of RASSF1A showed that 68.42% smoker and 75% non-smoker NPC’s patients were methylated. MSP analysis of CDKN2A showed that 21.05% smoker and 25% non-smoker NPC’s patients were methylated. There was no association between smoking behavior with RASSF1A and CDKN2A methylation (p>0.05). CONCLUSION: Statistical analysis showed that smoking behavior is not associated with methylation of RASSF1A and CDKN2A among NPC’s patients.KEYWORDS: DNA methylation, CDKN2A, RASSF1A, Nasopharyngeal carcinoma, Smoking
Activated monocytes and markers of inflammation in newly diagnosed multiple sclerosis

Abstract In multiple sclerosis (MS), the inflammation and demyelination of the central nervous system (CNS) develop in distinct ways. This makes diagnosing patients difficult, imperative to initiating early and proper treatment. Several common features exist, among them a profound infiltration of monocytes into the CNS mediating demyelination and tissue destruction. In the periphery, monocytes are divided into three subsets depending on expression of CD14 and CD16, representing different stages of activation and differentiation. To investigate their involvement in MS, peripheral blood mononuclear cells (PBMCs) from 61 patients with incipient, untreated MS and 22 symptomatic control (SC) patients as well as 6 patients with radiologically isolated syndrome (RIS) were characterized ex vivo. In addition, paired serum and cerebrospinal fluid (CSF) samples were analyzed with a panel of biomarkers. In PBMC samples, we demonstrate decreased levels of nonclassical monocytes with a concomitant significant decrease of human endogenous retrovirus (HERV) H3 envelope epitopes on this monocyte subset compared with SC and RIS. The observed HERV expression is present on nonclassical monocytes irrespective of MS and thus presumably a result of the inflammatory activation. For the other surface markers analyzed, we found significantly decreased expression between classical and nonclassical monocytes. In matched samples of CSF a highly significant increase in levels of soluble markers of activation and inflammation is shown, and notably this is not the case for the serum samples. Of the soluble markers investigated, interleukin (IL)‐12/IL‐23p40 had the highest discriminatory power in differentiating patients with MS from SC and RIS, almost comparable to the immunoglobulin G index.
Tumor microenvironment is critical for the maintenance of cellular states found in primary glioblastomas.

Glioblastoma, an incurable tumor, remains difficult to model and more importantly to treat due to its genetic/epigenetic heterogeneity and plasticity across cellular states. The ability of current tumor models to recapitulate the cellular states found in primary tumors remains unexplored. To address this issue, we compared single-cell RNA-sequencing of tumor cells from five patients across four patient-specific glioblastoma stem cell (GSC)-derived model types, including glioma spheres, tumor organoids, glioblastoma cerebral organoids (GLICO), and patient-derived xenografts. We find that GSCs within the GLICO model are enriched for a neural progenitor-like cell (NPC) subpopulation and recapitulate the cellular states and their plasticity found in the corresponding primary parental tumors. These data demonstrate how the contribution of a neuroanatomically accurate human microenvironment is critical and sufficient for recapitulating the cellular states found in human primary GBMs, a principle that may likely apply to other tumor models.
Comparison of pulmonary mechanics during isoflurane, sevoflurane, and desflurane anesthesia

Background: Practicing anesthesia clinicians are aware that tracheal intubation increases resistance and alters pulmonary mechanics; thus, comparison of bronchodilating effects of volatile agents is desirable. This study was aimed to compare the respiratory mechanics during isoflurane, sevoflurane, and desflurane anesthesia at 1 minimum alveolar concentration (MAC) and 2 MAC. Materials and Methods: Seventy patients undergoing moderate duration surgery were sequentially allocated into one of the three groups: Group I (Isoflurane; n = 23), Group S (Sevoflurane; n = 24), and Group D (Desflurane; n = 23). Peak inspiratory pressure (PIP), dynamic lung compliance (Cdyn), and airway resistance (Raw) values at three different time points were noted: 3 breaths after the start of mechanical ventilation (T1), 5 min after 1 MAC (T2), and 2 min after 2 MAC (T3). Results: PIP increased significantly in the desflurane group by 6% at 1 MAC and 8.06% at 2 MAC from the baseline. Statistically significant increase in Cdyn by 1.59% at 1 MAC and 9.9% at 2 MAC was found in sevoflurane group. Raw decreased significantly by 24.28% at 1 MAC and by 45.65% at 2 MAC from the baseline in sevoflurane group. Conclusions: We conclude that increasing concentrations from 1 MAC to 2 MAC show more consistent bronchodilating effect of Sevoflurane compared to isoflurane and desflurane. Sevoflurane increased Cdyn and reduced Raw from 1 MAC to 2 MAC.
Knowledge of Good Samaritan Laws and Beliefs About Arrests Among Persons Who Inject Drugs a Year After Policy Change in Baltimore, Maryland

Objectives Delivering and receiving prompt medical care during an overdose are imperative to ensure survival. Good Samaritan laws encourage people to call 911 during an overdose by providing immunity from selected drug arrests (eg, low-level possession). However, it is unclear whether persons who inject drugs (PWID) are aware of and understand these laws and their implications. We examined awareness among PWID of the 2015 Good Samaritan law in Maryland and their beliefs about whether they could be arrested for calling 911 or having an overdose. Methods We surveyed 298 PWID in Baltimore, Maryland. We estimated the proportion who knew what the Good Samaritan law addressed and who believed they could be arrested for calling 911 or overdosing. We used a multivariate model to assess the association between harm-reduction services and knowledge of the Good Samaritan law or beliefs about getting arrested for calling 911 or overdosing. Results Of PWID, 56 of 298 (18.8%) knew what the Good Samaritan law addressed, 43 of 267 (16.1%) believed they could be arrested for calling 911, and 32 of 272 (11.8%) believed they could be arrested for having an overdose. After adjusting for demographic characteristics, accessing the syringe services program was associated with accurate knowledge and the belief that PWID could be arrested for calling 911; however, training in overdose reversal was not associated. Conclusions Most PWID were unaware of the Good Samaritan law; this lack of awareness is a barrier to preventing overdose deaths. Educating PWID about Good Samaritan laws is essential, and such education should include police to ensure that law enforcement is congruent with Good Samaritan laws and does not perpetuate mistrust between police and PWID.
COVID‐19 and the use of immunomodulatory and biologic agents for severe cutaneous disease: An Australian/New Zealand consensus statement

Patients on immunomodulators, including biologic agents and new small molecular inhibitors, for cutaneous disease, represent a potentially vulnerable population during the COVID‐19 pandemic. There is currently insufficient evidence to determine whether patients on systemic immunomodulators are at increased risk of developing COVID‐19 disease or more likely to have severe disease. As such, clinicians need to assess the benefit‐to‐risk ratio on a case‐by‐case basis. In patients with suspected or confirmed COVID‐19 disease, all immunomodulators used for skin diseases should be immediately withheld, with the possible exception of systemic corticosteroid therapy, which needs to be weaned. In patients who develop symptoms or signs of an upper respiratory tract infection, but COVID‐19 is not yet confirmed, consider dose reduction or temporarily cessation for 1–2 weeks. In otherwise well patients, immunomodulators and biologics should be continued. In all patients, and their immediate close contacts, the importance of preventative measures to minimise human‐to‐human transmission cannot be overemphasised.
Correlation between degree of hallux valgus and kinematics in classical ballet: A pilot study

Hallux valgus is a serious medical concern for classical ballet dancers. Although it is well-known that progression of hallux valgus is related to inappropriate movement techniques in classical ballet, the kinematic relationship between the degree of hallux valgus and ballet techniques has not been substantiated. To develop proper training methods that prevent progression of hallux valgus, this study aimed to investigate the relationship between the degree of hallux valgus and movement techniques in classical ballet. Seventeen female classical ballet dancers at the advanced college-level participated in this study. Kinematic analysis of standing and plié in the first position was conducted via video capture technique. The Pearson product-moment correlation analysis was performed to examine the degree of hallux valgus and the following three kinematic variables: (1) the extent to which turnout is forced by other joints in the lower extremity than the hip joint, (2) the direction difference between the knee and toe in the transverse plane, and (3) the pelvis obliquity angle. Among these kinematic variables, we found a significant correlation between the hallux valgus angle and the pelvis obliquity angle during plié (P = .045). The greater the hallux valgus angle, the greater the retroversion of the pelvis, a result which was contrary to our prediction. We present the first evidence that the degree of hallux valgus correlates with kinematics in a very basic technique of classical ballet.
Automatic heart sound classification from segmented/unsegmented phonocardiogram signals using time and frequency features

Objective: Heart abnormality detection using heart sound signals (phonocardiogram (PCG)) has been an active research area for the last few decades. In this paper, automatic heart sound classification using segmented and unsegmented PCG signals is presented. Approach: In this paper: (i) we perform an in-depth analysis of various time and frequency domain features, followed by experimental determination of effective feature subsets for improved classification performance; (ii) both segmented and unsegmented PCG signals are studied and important results concerning the respective feature subsets and their classification performances are reported; and (iii) different classification algorithms, including the support vector machine, kth nearest neighbor, decision tree, ensemble classifier, artificial neural network and long short-term memory network (LSTMs), are employed to evaluate the performance of the proposed feature subsets and their comparison with other established features and methods is presented. Main results: It is observed that LSTM performs better on mel-frequency cepstral coefficient (MFCC) features extracted from unsegmented PCG data, with an area under curve (AUC) score of 91.39%, however, the MFCC features do not show a consistent performance with other classifiers (the second highest AUC score is 62.08% with the decision tree classifier). In contrast, in the case of time-frequency features from segmented data, the performance of all the classifiers is appreciable with AUC scores over 70%. In particular, the conventional machine learning techniques shows consistency in achieving over 80% in AUC scores. Significance: The results of this study highlight the importance of time and frequency domain features. Thus it is necessary to employ both the time and frequency features of segmented PCG signals to achieve improved classification.
Structural Characterization of the N-Terminal Domain of the Dictyostelium discoideum Mitochondrial Calcium Uniporter

The mitochondrial calcium uniporter (MCU) plays a critical role in the mitochondrial calcium uptake into the matrix. In metazoans, the uniporter is a tightly regulated multi-component system including the pore-forming subunit MCU and several regulators (MICU1, MICU2, EMRE). The calcium-conducting activity of metazoan MCU requires the single-transmembrane protein EMRE. Dictyostelium discoideum (Dd), however, developed a simplified uniporter for which the pore-forming MCU (DdMCU) alone is necessary and sufficient for calcium influx. Here, we report a crystal structure of the N-terminal domain (NTD) of DdMCU at 1.7 Å resolution. The DdMCU-NTD contains four helices and two strands arranged in a fold that is completely different from the known structures of other MCU-NTD homologs. Biochemical and biophysical analyses of DdMCU-NTD in solution indicated that the domain exists as oligomers, most probably as a pentamer or hexamer. Mutagenesis showed that the acidic residues Asp60, Glu72 and Glu74, which appeared to mediate the parallel interface as observed in the crystal structure, participated in the self-assembly of DdMCU-NTD. Intriguingly, the oligomeric complex readily dissociated to lower-order oligomers in the presence of calcium. We propose that the calcium-triggered dissociation of NTD regulates the channel activity of DdMCU by a yet unknown mechanism.
Save Muscle Information–Unfiltered EEG Signal Helps Distinguish Sleep Stages

Based on the well-established biopotential theory, we hypothesize that the high frequency spectral information, like that higher than 100Hz, of the EEG signal recorded in the off-the-shelf EEG sensor contains muscle tone information. We show that an existing automatic sleep stage annotation algorithm can be improved by taking this information into account. This result suggests that if possible, we should sample the EEG signal with a high sampling rate, and preserve as much spectral information as possible.
Directing 2D-Coordination Networks: Combined Effects of a Conformationally Flexible 3,2′:6′,3″-Terpyridine and Chain Length Variation in 4′-(4-n-Alkyloxyphenyl) Substituents

The synthesis and characterization of 4′-(4-n-propoxyphenyl)-3,2′:6′,3″-terpyridine is described. Five 2D-coordination networks have been isolated by crystal growth at room temperature from reactions of Co(NCS)2 with 4′-(4-n-alkyloxyphenyl)-3,2′:6′,3″-terpyridines in which the n-alkyl group is ethyl, n-propyl, n-butyl, n-pentyl and n-hexyl in ligands 2–6, respectively. The single-crystal structures of [{Co(2)2(NCS)2}. 0.6CHCl3]n, [{Co(3)2(NCS)2}. 4CHCl3.0. 25H2O]n, [{Co(4)2(NCS)2}. 4CHCl3]n, [Co2(5)4(NCS)4]n and [Co(6)2(NCS)2]n have been determined, and powder X-ray diffraction has demonstrated that the single-crystal structures are representative of the bulk materials. Each compound possesses a (4,4) net with Co centres as 4-connecting nodes. For the assemblies containing 2, 3 and 4, the (4,4) net comprises two geometrically different rhombuses, and the nets pack in an ABAB. arrangement with cone-like arrangements of n-alkyloxyphenyl groups being accommodated in a similar unit in an adjacent net. An increase in the n-alkyloxy chain length has two consequences: there is a change in the conformation of the 3,2′:6′,3″-tpy metal-binding domain, and the (4,4) net comprises identical rhombuses. Similarities and differences between the assemblies with ligands 2–6 and the previously reported [{Co(1)2(NCS)2}. 3MeOH]n and [{Co(1)2(NCS)2}. 2.2CHCl3]n in which 1 is 4′-(4-methoxyphenyl)-3,2′:6′,3″-terpyridine are discussed. The results demonstrate the effects of combining a variable chain length in the 4′-(4-n-alkyloxyphenyl) substituents of 3,2′:6′,3″-tpy and a conformationally flexible 3,2′:6′,3″-tpy metal-binding domain.
Relationship between final adult height and birth weight after gonadotropin-releasing hormone agonist treatment in girls with central precocious puberty

Purpose The clinical significance of birth weight relative to gestational age in girls with central precocious puberty is unclear. This study sought to compare clinical parameters such as final adult height (FAH) and menarche onset after treatment with gonadotropin-releasing hormone agonist (GnRHa) on birth weight in girls with central precocious puberty treated. Methods This retrospective study reviewed data of 69 girls with precocious puberty who had reached their FAH in a long-term trial of GnRHa treatment between January 2007 and December 2017. The subjects were divided into small for gestational age (SGA) (n=19) and appropriate for gestational age (AGA) (n=50) groups. Results When starting GnRHa treatment, bone age was 10.9±0.9 and 10.3±0.8 years in the SGA and AGA groups, respectively (P<0.05). The predicted adult height (PAH) (established according to the Bayley-Pinneau average table) and advanced PAH (established according to the Bayley-Pinneau advanced table) were 151.5±4.8 cm and 155.8±4.9 cm in the SGA group, respectively, and 153.4±5.3 cm and 159.0±6.0 cm in the AGA group. After treatment, no significant difference in bone age was found between the groups. The time to menarche after treatment was 12.5±7.6 and 21.1±12.3 months in the SGA and AGA groups, respectively (P<0.05). FAH in the SGA and AGA groups was 161.0±4.7 cm and 161.6±5.0 cm, respectively, without a significant difference. Conclusions SGA girls with precocious puberty have increased bone age and earlier menarche relative to AGA girls. However, no difference in FAH after treatment was found between these groups.
In Vitro Diagnostic Assays for COVID-19: Recent Advances and Emerging Trends

There have been tremendous advances in in vitro diagnostic (IVD) assays for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The main IVD assays used for COVID-19 employ real-time reverse transcriptase polymerase chain reaction (RT-PCR) that takes a few hours. But the assay duration has been shortened to 45 min by Cepheid. Of interest is the point-of-care (POC) molecular assay by Abbott that decreased the assay duration to just 5 min. Most molecular tests have been approved by the United States Food and Drug Administration (FDA) under emergency use authorization (EUA) and are Conformité Européenne (CE) marked. A wide range of serology immunoassays (IAs) have also been developed that complement the molecular assays for the diagnosis of COVID-19. The most prominent IAs are automated chemiluminescent IA (CLIA), manual ELISA, and rapid lateral flow IA (LFIA), which detect the immunoglobulin M (IgM) and immunoglobulin G (IgG) produced in persons in response to SARS-CoV-2 infection. The ongoing research efforts and advances in complementary technologies will pave the way to new POC IVD assays in the coming months. However, the performance of IVD assays needs to be critically evaluated before they are employed for the clinical diagnosis of COVID-19.