Miracle-dz/UniFAR-FTUs huggingface dataset:
Cost-Effectiveness Analysis of Maintenance Olaparib in Patients with Metastatic Pancreatic Cancer and a Germline BRCA1/2 Mutation Based on the POLO Trial

Objective The phase III POLO trial demonstrated that olaparib as maintenance therapy for metastatic pancreatic cancer patients with a germline BRCA mutation had greater efficacy than placebo, but maintenance olaparib places an economic burden on patients. This study evaluated the cost-effectiveness of olaparib as maintenance therapy based on the POLO trial (NCT02184195). Methods A three-state Markov model (progression-free survival [PFS], progressive disease [PD] and death) based on data from the POLO trial was used to estimate the incremental cost-effectiveness ratio (ICER) of maintenance olaparib versus placebo for metastatic pancreatic cancer patients with a germline BRCA mutation. The cost was evaluated from the Chinese society’s perspective, and health outcomes were assessed in terms of quality-adjusted life years (QALYs). The primary outcome was the ICER gained in terms of 2019 US$ per QALY. Model robustness was explored with one-way and probabilistic sensitivity analyses. Results Compared with placebo, maintenance olaparib increased costs by $23,544.35 while gaining 0.69 QALYs, resulting in an ICER of $34,122.25 per QALY. The ICER was far higher than the commonly accepted willingness-to-pay threshold ($28,255.55 per QALY). Conclusion Compared with placebo, maintenance olaparib for metastatic pancreatic cancer patients with a germline BRCA mutation is not cost-effective in China.
The complete chloroplast genome of Phellodendron chinense (Rutaceae), an Endangered medicinal plant in southern China

Abstract Phellodendron chinense is an Endangered medicinal plant in southern China. In this study, the complete chloroplast genome sequence of P.chinense was characterized by de novo assembly. The length of the whole chloroplast genome was 158,537 bp, containing a large single copy region (LSC) of 86,250 bp and a small single copy region (SSC) of 18,287 bp, which were separated by a pair of 27,000 bp inverted repeat regions (IRs). The sequence contains 114 unique genes, including 30 tRNA, 4 rRNA, and 80 protein-coding genes. The overall GC content of the chloroplast genome is 38.4% and those in the LSC, SSC, and IR regions are 36.6, 33.2, and 42.9%, respectively. The phylogenetic analysis based on reported chloroplast sequences of Rutaceae showed that P. chinense is sister to P. amurense, consisting a monophyletic group, and that Phellodendron is closely related to Zanthoxylum.
The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders

Purpose The Vagus Nerve Stimulation (VNS) Therapy System has been studied for more than 20 years in patients with severe, treatment-resistant, chronic mood disorder, i.e., difficult-to-treat depression (DTD). This review distills some of the implications of this research for future therapeutic trials in this population. Methods A narrative review is provided on VNS in DTD. Protocols for a new, large, sham-controlled trial and a global, longitudinal observational study are described. Results Following encouraging results in open studies, a randomized, masked, sham-controlled trial of VNS for DTD failed to demonstrate an effect on the primary outcome. The negative results may have been partly due to inadequate treatment duration (10 weeks). In long-term observational studies, adjunctive VNS, combined with treatment-as-usual (VNS+TAU), was administered to more than 1100 DTD patients and compared with TAU alone in more than 400 patients. VNS+TAU had superior antidepressant effects, but maximal symptom reduction was often observed after 12 months or longer of stimulation. VNS+TAU had also marked superiority in durability of benefit. Sustained levels of symptom reduction below the traditional cutoff for response (i.e. < 50%) were associated with improved quality of life. Limitations Most comparisons of VNS+TAU and TAU were derived from observational, open label studies. Conclusion The history of VNS in DTD has implications for interventional studies in this population, and perhaps other chronic medical disorders. The slow onset of benefit with VNS necessitates considerably longer controlled observation periods to establish efficacy. Durability of benefit should be routinely incorporated in efficacy assessment. New outcome metrics are needed to both categorically identify clinically meaningful benefit and to integrate information on symptom burden over time.
Structural Modeling of Wild and Mutant Forms of Human Plasma Platelet Activating Factor-Acetyl Hydrolase Enzyme

Purpose To investigate the structural features of wild and mutant forms of the pPAF-AH enzyme that are responsible for coronary artery disease. Methods Mutant variants of human pPAF-AH having either V279F, Q281R, or both were modelled and evaluated for stereo chemical and structural correctness. The 3D coordinates of substrate PAF were retrieved from the PubChem database was solvated and minimized on Discovery Studio, and docked to the wild and mutant enzyme models. The top docked pose complex was refined by MD simulation. Results pPAF-AH model comprises of 420 amino acids in a α/β-hydrolase fold that contains a substrate-binding hydrophobic channel with an active site pocket having a catalytic triad of Ser273, Asp296 and His351. Mutations at positions 279 and 281 are opposite one another on the middle of 12 residues long H5 helix that forms the hydrophobic core of the enzyme. V279F causes a tilt on the axis of the mutation bearing helix to avoid steric clashes with the hydrophobic residues on the β-sheets adjacent to it, inducing subtle conformational changes on the H5-β8 loop, β8 sheet, and the loop bearing Asp296. A cascade of conformational changes induces a change in the orientation of His351 resulting in loss of hydrogen bonded interaction with catalytic Ser273. Q281R causes a shortening of H5 and β8, which induces conformational changes of the loops bearing Ser273 and Asp296, respectively. Simultaneous conformational changes of secondary structural elements result in the flipping of His351 causing a break in the catalytic triad. Also, there is a compromise in the substrate-binding area and volume in the mutants resulting in loss of binding to its substrate. Conclusion Mutant enzymes show changes at the site of the mutation, secondary motif conformations and global structural conformations that adversely affect the active site, decrease substrate channel volume and decrease stability, thereby affecting enzymatic function.
The complete chloroplast genome sequence of Knema conferta (Myristicaceae)

Abstract Knema conferta is a member of Myristicaceae. The K. conferta chloroplast genome is found to be 155,744 bp in length and has a base composition of A (30.02%), G (19.30%), C (19.90%), and T (30.78%). The genome contained two short inverted repeat (IRa and IRb) regions (48,052 bp) which were separated by a large single copy (LSC) region (86,926 bp) and a small single copy (SSC) region (20,770 bp). The genome encoded a total of 128 unigenes, including 89 protein-coding genes, 31 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. Further, complete chloroplast sequence of K. conferta was aligned together with 2 species of Knema and 5 basal angiosperms species which have reported the complete chloroplast sequence. This complete chloroplast genome will provide valuable information for the development of DNA markers for future species resource development and phylogenetic analysis of K. conferta.
Human Adipose-Derived Mesenchymal Stem Cells-Derived Exosomal microRNA-19b Promotes the Healing of Skin Wounds Through Modulation of the CCL1/TGF-β Signaling Axis

Introduction Human adipose-derived mesenchymal stem cells (ADMSCs) with their secretory factors are able to induce collagen synthesis and fibroblast migration in the wound healing process. This study is launched to figure out the effect of human ADMSCs-derived exosomes on skin wound healing. Methods ADMSCs were extracted and ADMSCs-derived exosomes were identified. Skin damage models were established by treating HaCaT cells and human skin fibroblasts with H2O2. Next, the roles of ADMSCs and their derived exosomes were investigated. The exosomal miRNA then was analyzed, and the function of miRNA on the H2O2-induced cells was studied by miRNA suppression. Bioinformatics analysis, luciferase activity and RIP assays were implemented to find the target genes ofthe miRNA and the modulated pathways. A mouse skin damage model was induced to elucidate the effects of exosomes in vivo by injecting exosomes. Results H2O2 treatment significantly reduced the viability of HaCaT cells and increased their apoptosis rate. Co-culture with ADMSCs or their derived exosomes could improve the cell damage caused by H2O2. Meanwhile, H2O2 treatment promoted the internalization of exosomes. ADMSCs and their derived exosomes significantly increased miR-19b expression in the recipient cells, while inhibiting miR-19b resulted in a reduction in the therapeutic effect of ADMSCs-derived exosomes. Besides, miR-19b regulated the TGF-β pathway by targeting CCL1. The therapeutic effect of exosomes was further confirmed by a mouse model of skin damage. Conclusion Our study indicates that exosomal miR-19b derived from ADMSCs regulates the TGF-β pathway by targeting CCL1, thereby promoting the healing of skin wounds.
Respectful Maternity Care and Associated Factors Among Women Who Attended Delivery Services in Referral Hospitals in Northwest Amhara, Ethiopia: A Cross-Sectional Study

Background Disrespectful and abusive care is a violation of women rights to self-determination, health, life, body integrity, and privacy. Providing respectful maternity care (RMC) during labour and delivery is one of the enhancing factors and targets in the Ethiopian health sector strategic plan to promote facility delivery. However, providing respectful maternity care is still a major challenge in the Ethiopia health-care system. This study aimed to assess respectful maternity care and associated factors among women who attended delivery services in Northwest Amhara, referral hospitals, Ethiopia. Methods Health-facility-based cross-sectional study was conducted at Northwest Amhara, referral hospitals from March 1 to April 1, 2020. A systematic random sampling technique was used to identify study participants in the referral hospitals. A total of 410 women who gave birth were enrolled in the study. A pre-tested and structured questionnaire was used for data collection. The data were collected during the exit interview. Data were cleaned and entered into Epi data version 3.1 and exported to SPSS version 23 for further analysis. Both bi-variable and multi-variable logistic regressions were employed in the analysis. Variables with a p-value of less than 0.05 were used to declare as statistically significantly associated with the dependent variable. Results The overall magnitude of women who have received respectful maternity care was 56.3%. Four and above antenatal care follow-up adjusted odds ratio (AOR) 3.092 (95% CI: 1.676, 5.725), previous history of facility delivery AOR 2.53 (95% CI: 1.094, 5.867), and delivery time AOR 2.46 (95% CI: 1.349, 4.482) were found significantly associated with respectful maternity care. Conclusion The overall magnitude of respectful maternity care was low as compared to international and national standards. This study showed that respectful maternity care among women who gave birth was influenced by the number of antenatal care visits, previous history of facility delivery, and delivery time.
A Novel Prognostic Score Based on ZG16 for Predicting CRC Survival

Background Colorectal cancer (CRC) is one of the lethal malignant tumors worldwide. However, the underlying mechanism of CRC and its biomarkers remain unclear. The aim of this study was to identify the key genes associated with CRC and to further explore their prognostic significance. Methods Four expression profile datasets (GSE41657, GSE74602, GSE113513, and GSE40967) downloaded from Gene Expression Omnibus (GEO) and one RNAseq dataset of CRC from The Cancer Genome Atlas (TCGA) database were included in our study. The Cox model was utilized for univariate or multivariate survival analysis. GEPIA and HAP database were adopted for verification of DEGs (ZG16). The decision curve analysis (DCA) and time-dependent ROC were chosen for evaluating the prognostic effectiveness of biomarkers. Results In total, 88 differentially expressed genes (DEGs) were identified, and the GO and KEGG enrichment analyses of DEGs were processed. After, the protein–protein interaction (PPI) network was constructed and 15 hub genes including ZG16 were identified. The differential expression of ZG16 between tumor and normal colorectal tissues were further verified in GEPIA and HAP database. Subsequent survival indicated that expression of ZG16 is negatively correlated with overall survival of OS and is an independent prognostic factor for CRC patients. Furthermore, the construction of a prognostic score containing ZG16, TNM stage and age exhibited superior effectiveness for predicting long-term survival of CRC patients. Additionally, our results were verified using the GSE40967 dataset, which indicated an improved performance of combined risk score based on ZG16 for predicting OS of CRC patients. Conclusion ZG16 is a potential parameter for predicting prognosis in CRC. Furthermore, a combination of ZG16, TNM stage, and age allows improved prognosis of CRC.
The Natural History and Transmission Potential of Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Abstract Background Little is known about the natural history of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods We conducted a prospective study at a quarantine center for coronavirus disease 2019 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with reverse-transcription polymerase chain reaction (RT-PCR)–confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrollment and daily nasopharyngeal/throat swabs (NTSs) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals. Results Between 10 March and 4 April 2020, 14 000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13 (43%) never had symptoms and 17 (57%) were symptomatic. Seventeen (57%) participants imported cases. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS collected at enrollment (8/13 [62%] vs 17/17 [100%]; P = .02). SARS-CoV-2 RNA was detected in 20 of 27 (74%) available saliva samples (7 of 11 [64%] in the asymptomatic group and 13 of 16 [81%] in the symptomatic group; P = .56). Analysis of RT-PCR positivity probability showed that asymptomatic participants had faster viral clearance than symptomatic participants (P < .001 for difference over the first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit SARS-CoV-2 to 4 contacts. Conclusions Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTSs. The NTS viral loads fall faster in asymptomatic individuals, but these individuals appear able to transmit the virus to others.
Visualizing pathogens: Disfluent shapes of pathogens increase their perceived complexity and danger while realism and disfluency boost the credibility of visualizations

Abstract During the COVID‐19 pandemic, the public was regularly presented with visualizations of the viral pathogen causing this disease. Since there are several ways of visually communicating information, we investigate whether different types of visualizations affect how viewers judge the credibility of information as well as the complexity and potential harm of pathogens. A first experiment was conducted to assess whether a round, fluent shape elicits a different response than pathogens featuring disfluent components such as thread‐like appendages. Visualizations of disfluent bacteria were rated as more credible than those of fluent bacteria. In Experiment 2, bacteria were either presented as realistic renderings or as cartoon‐like line drawings (varied between‐subjects). Furthermore, half of the six bacteria had fluent shapes, while the other half featured disfluent shapes, resulting in the within‐subjects factor of fluency. Participants were asked to rate the credibility, complexity, and risk of serious illness associated with these bacteria. We found that disfluent bacteria were perceived as having a more complex metabolism and as holding a higher risk for serious illness. Furthermore, realism and disfluent shapes increase the credibility of visualizations, but not the credibility of additional information. These results have important implications for the field of science communication.
Conversion of atmospheric dioxygen to a µ–η2,η2-peroxo bridge in a dinuclear uranium(VI) complex

N, N-Ethylenebis(2-pyrrolidone)(ebpyrr) reacts with uranyl nitrate in acetonitrile, methanol, or nitromethane to form a helical chain polymer [UO2(NO3)2(ebpyrr)]n and, on exposure to air, also a dinuclear µ-η2, η2-peroxo-bridged complex {[(UO2)(NO3)(ebpyrr)]2(µ-O2)}.
SIMDRAM: A Framework for Bit-Serial SIMD Processing Using DRAM

Processing-using-DRAM has been proposed for a limited set of basic operations (i.e., logic operations, addition). However, in order to enable the full adoption of processing-using-DRAM, it is necessary to provide support for more complex operations. In this paper, we propose SIMDRAM, a flexible general-purpose processing-using-DRAM framework that enables massively-parallel computation of a wide range of operations by using each DRAM column as an independent SIMD lane to perform bit-serial operations. SIMDRAM consists of three key steps to enable a desired operation in DRAM: (1) building an efficient majority-based representation of the desired operation, (2) mapping the operation input and output operands to DRAM rows and to the required DRAM commands that produce the desired operation, and (3) executing the operation. These three steps ensure efficient computation of any arbitrary and complex operation in DRAM. The first two steps give users the flexibility to efficiently implement and compute any desired operation in DRAM. The third step controls the execution flow of the in-DRAM computation, transparently from the user. We comprehensively evaluate SIMDRAM's reliability, area overhead, operation throughput, and energy efficiency using a wide range of operations and seven diverse real-world kernels to demonstrate its generality. Our results show that SIMDRAM provides up to 5.1x higher operation throughput and 2.5x higher energy efficiency than a state-of-the-art in-DRAM computing mechanism, and up to 2.5x speedup for real-world kernels while incurring less than 1% DRAM chip area overhead. Compared to a CPU and a high-end GPU, SIMDRAM is 257x and 31x more energy-efficient, while providing 93x and 6x higher operation throughput, respectively.
LIMITATIONS AND PROSPECTS OF BIOLOGICAL ELECTRON PROBE X-RAY MICROANALYSIS

ABSTRACT Analytical electron microscopy is used to identify, localize and quantify chemical elements in biological samples with the aim to correlate the element distribution in cells and tissues with the particular functional state. Energy dispersive electron probe X-ray microanalysis of freeze-dried cryosections is considered to be the most efficient technique with respect to spatial analytical resolution and detection limit. The potentialities and limitations of this technique are illustrated by results from 3 current research projects: Element compartmentation in hepatocytes, cytotoxicity of an organotin compound, and calcium movements during osmoregulation of epithelia. At present, the absolute detection limit is 170 atoms in a minimum analytical volume of 30 × 30 × 100 nm3. X-ray microanalysis of cryosections from biological samples is limited by ice crystal growth during cryofixation and by the poor X-ray collection efficiency in most electron microscopes. Therefore, the construction of an analytical electron microscope dedicated to biological X-ray microanalysis is proposed. This microscope features considerably improved X-ray collection efficiency due to an annular X-ray detector. The absolute detection limit is estimated to be less than 10 atoms in a minimal analytical volume of 10 × 10 × 100 nm3 of a cryosection.
Resveratrol, Rapamycin and Metformin as Modulators of Antiviral Pathways

Balanced nutrition and appropriate dietary interventions are fundamental in the prevention and management of viral infections. Additionally, accurate modulation of the inflammatory response is necessary to achieve an adequate antiviral immune response. Many studies, both in vitro with mammalian cells and in vivo with small animal models, have highlighted the antiviral properties of resveratrol, rapamycin and metformin. The current review outlines the mechanisms of action of these three important compounds on the cellular pathways involved with viral replication and the mechanisms of virus-related diseases, as well as the current status of their clinical use.
Acrylamide–Hemoglobin Adduct Levels in a Japanese Population and Comparison with Acrylamide Exposure Assessed by the Duplicated Method or a Food Frequency Questionnaire

The levels of hemoglobin adducts of acrylamide (AA–Hb), a biomarker of acrylamide exposure, have not been reported for Japanese subjects. Herein, we determined the AA–Hb levels in a Japanese population and compared them with the estimated dietary intake from the duplicate diet method (DM) and a food frequency questionnaire (FFQ). One-day DM samples, FFQ, and blood samples were collected from 89 participants and analyzed for acrylamide. AA–Hb was analyzed using liquid chromatography tandem mass spectrometry and the N-alkyl Edman method. Participants were divided into tertiles of estimated acrylamide intake and geometric means (GMs) of AA–Hb adjusted for sex and smoking status. A stratified analysis according to smoking status was also performed. The average AA–Hb levels for all participants, never, past, and current smokers were 46, 38, 65, and 86 pmol/g Hb, respectively. GMs of AA–Hb levels in all participants were significantly associated with tertiles of estimated acrylamide intake from DM (p for trend = 0.02) and FFQ (p for trend = 0.04), although no association with smokers was observed. AA–Hb levels reflected smoking status, which were similar to values reported in Western populations, and they were associated with estimated dietary intake of acrylamide when adjusted for sex and smoking status.