Miracle-dz/UniFAR-FTUs huggingface dataset:
Systematic review and quality evaluation of published human ingestion-time trials of blood pressure-lowering medications and their combinations

ABSTRACT The pharmacokinetics (PK) – absorption, distribution, metabolism, and elimination – and pharmacodynamics (PD) of hypertension medications can be significantly affected by circadian rhythms. As a consequence, the time when blood pressure (BP) lowering medications are ingested, with reference to the staging of all involved circadian rhythms modulating PK and PD, can affect their duration of action, magnitude of effect on features of the 24 h BP profile, and safety. We conducted a systematic and comprehensive review of published prospective human trials that investigated individual hypertension medications of all classes and their combinations for ingestion-time differences in BP-lowering, safety, patient adherence, and markers of hypertension-associated target organ pathology of the kidney and heart. The systematic review yielded 155 trials published between 1976 and 2020 – totaling 23,972 hypertensive individuals – that evaluated 37 different single and 14 dual-combination therapies. The vast (83.9%) majority of them reported clinically and statistically significant benefits – including enhanced reduction of asleep BP mean without induced sleep-time hypotension, reduced prevalence of the higher cardiovascular risk non-dipper 24 h BP profile, decreased incidence of adverse effects, improved kidney function, and reduced cardiac pathology – when hypertension medications are ingested at-bedtime/evening rather than upon-waking/morning. Nonetheless, the findings and conclusions of some past conducted trials are inconsistent, often due to disparities and deficiencies of the investigative protocols. Accordingly, we developed a quality assessment method based upon the eight items identified as crucial according to the recently published guidelines of the International Society for Chronobiology and the American Association for Medical Chronobiology and Chronotherapeutics for the design and conduct of human clinical trials on ingestion-time differences of hypertension medications. Among the most frequent deficiencies are: absence or miscalculation of minimum required sample size (83.2%), incorrect choice of primary BP endpoint (53.6%), and inappropriate arbitrary and unrepresentative clock hours chosen for tested treatment times (53.6%). The inability of the very small proportion (16.1%) of trials to verify the advantages of the at-bedtime/evening treatment strategy is likely explained by deficiencies of their study design and conduct. Nonetheless, regardless of the quality score of the 155 trials retrieved by our systematic review, it is most noteworthy that no single published prospective randomized trial reported significantly enhanced BP-lowering, safety, compliance, or other benefits of the unjustified by medical evidence, yet still most recommended, upon-waking/morning hypertension treatment-time scheme.
Pursuing breath research in unprecedented circumstances—report from the Breath Biopsy Conference 2020

The global outbreak of Sars-CoV-2 commencing early in 2020 had a dramatic impact on breath research, imposing abrupt restrictions but also presenting unforeseen opportunities. Taking place against the background of the COVID-19 pandemic, the 2020 Breath Biopsy Conference provided the breath research community with a platform to showcase and discuss the latest findings, including COVID-19 related research. As with most conferences under the present circumstance, it differed from its predecessor meetings by shifting to a virtual format, but retained its broad scope and interactive nature. The conference centred on four key themes, featuring applications of volatile organic compounds, breath biomarkers for liver disease, study design and data analytics, and, notably this year, breath-based endeavours to detect COVID-19 infection. This meeting report summarizes the events of the conference and spotlights selected contributions.
Evaluation of a Multimodal Heparin Laboratory Monitoring Protocol in Adult Extracorporeal Membrane Oxygenation Patients

Background: Anticoagulation monitoring practices vary during extracorporeal membrane oxygenation (ECMO). The Extracorporeal Life Support Organization describes that a multimodal approach is needed to overcome assay limitations and minimize complications. Objective: Compare activated clotting time (ACT) versus multimodal approach (activated partial thromboplastin time (aPTT)/anti-factor Xa) for unfractionated heparin (UFH) monitoring in adult ECMO patients. Methods: We conducted a single-center retrospective pre- (ACT) versus post-implementation (multimodal approach) study. The incidence of major bleeding and thrombosis, blood product and antithrombin III (ATIII) administration, and UFH infusion rates were compared. Results: Incidence of major bleeding (69.2% versus 62.2%, p = 0.345) and thrombosis (23% versus 14.9%, p = 0.369) was similar between groups. Median number of ATIII doses was reduced in the multimodal group (1.0 [IQR 0.0-2.0] versus 0.0 [0.0 -1.0], p = 0.007). The median UFH infusion rate was higher in the ACT group, but not significant (16.9 [IQR 9.6-22.4] versus 13 [IQR 9.6-15.4] units/kg/hr, p = 0.063). Fewer UFH infusion rate changes occurred prior to steady state in the multimodal group (0.9 [IQR 0.3 -1.7] versus 0.1 [IQR 0.0-0.2], p < 0.001). Conclusion: The incidence of major bleeding and thrombosis was similar between groups. Our multimodal monitoring protocol standardized UFH infusion administration and reduced ATIII administration.
The impact of girl child marriage on the completion of the first cycle of secondary education in Zimbabwe: A propensity score analysis

Background The association between girl child marriage and education is widely acknowledged; however, there is no large body of demographic studies from Zimbabwe that have addressed this aspect. This study aimed to examine the extent to which child marriage affects one academic milestone, i.e. completion of the Ordinary Level, the first cycle of high school, which is also the most critical indicator of educational achievement in Zimbabwe. Methods We used the 2015 Zimbabwe Demographic and Health Survey and extracted 2380 cases of ever-married women aged between 20–29 years. We applied a propensity score-based method, which allowed us to mimic a hypothetical experiment and estimate outcomes between treated and untreated subjects. Results Our results suggest that child age at first marriage is concentrated between the ages of 15–22, with the typical age at first marriage being 18 years. Both logistic regression and PSM models revealed that early marriage decreased the chances of completing the first cycle of high school. Regression adjustment produced an estimate of prevalence ratio (PR) of 0.446 (95% CI: 0.374–0.532), while PSM resulted in an estimate (PR = 0.381; 95% CI: 0.298–0.488). Conclusion These results have implications for Zimbabwe’s development policy and suggest that girl-child marriage is a significant barrier to educational attainment. If not addressed, the country will most likely fail to meet sustainable development Goal 4.2 and 5.3. Social change interventions that target adults and counter beliefs about adolescent sexuality and prepubescent marriage should be put in place. Moreover, interventions that keep teenage girls in school beyond the first cycle of high school should be prioritised.
An anchored chromosome‐scale genome assembly of spinach improves annotation and reveals extensive gene rearrangements in euasterids

Spinach (Spinacia oleracea L.) is a member of the Caryophyllales family, a basal eudicot asterid that consists of sugar beet (Beta vulgaris L. subsp. vulgaris), quinoa (Chenopodium quinoa Willd.), and amaranth (Amaranthus hypochondriacus L.). With the introduction of baby leaf types, spinach has become a staple food in many homes. Production issues focus on yield, nitrogen‐use efficiency and resistance to downy mildew (Peronospora effusa). Although genomes are available for the above species, a chromosome‐level assembly exists only for quinoa, allowing for proper annotation and structural analyses to enhance crop improvement. We independently assembled and annotated genomes of the cultivar Viroflay using short‐read strategy (Illumina) and long‐read strategies (Pacific Biosciences) to develop a chromosome‐level, genetically anchored assembly for spinach. Scaffold N50 for the Illumina assembly was 389 kb, whereas that for Pacific BioSciences was 4.43 Mb, representing 911 Mb (93% of the genome) in 221 scaffolds, 80% of which are anchored and oriented on a sequence‐based genetic map, also described within this work. The two assemblies were 99.5% collinear. Independent annotation of the two assemblies with the same comprehensive transcriptome dataset show that the quality of the assembly directly affects the annotation with significantly more genes predicted (26,862 vs. 34,877) in the long‐read assembly. Analysis of resistance genes confirms a bias in resistant gene motifs more typical of monocots. Evolutionary analysis indicates that Spinacia is a paleohexaploid with a whole‐genome triplication followed by extensive gene rearrangements identified in this work. Diversity analysis of 75 lines indicate that variation in genes is ample for hypothesis‐driven, genomic‐assisted breeding enabled by this work.
The effects of psychotherapies for depression on response, remission, reliable change, and deterioration: A meta‐analysis

Meta‐analyses of psychotherapies usually report effects sizes, while clinicians and patients need to know the proportion of patients who benefit from therapy. We conducted a meta‐analysis of therapies for depression reporting the rates of response (50% symptom reduction), remission (HAM‐D <7), clinical significant deterioration for psychotherapy, and control conditions (CAU, waitlist, and pill placebo), as well as the relative risk of these outcomes and the numbers‐needed‐to‐be‐treated (NNTs).
LncRNA PCBP1-AS1 correlated with the functional states of cancer cells and inhibited lung adenocarcinoma metastasis by suppressing the EMT progression.

The development of single-cell RNA sequencing (scRNA-seq) provided us an unprecedented chance to identify novel oncogenes or tumor suppressors at single-cell resolution. Long non-coding RNAs (lncRNAs) related to the functional states of cancer cells might play vital roles in the progression of lung adenocarcinoma (LUAD). In this study, LncRNAs that were associated with the functional states of LUAD cells identified in scRNA-seq studies were screened based on the CancerSEA database. Differential gene expression analysis and survival analysis were performed in TCGA, GEO and our JSPH databases. Finally, transwell and tail vein metastasis assays were used to reveal the functions of our identified novel prognostic lncRNAs. A total of 849 lncRNAs were initially identified. Among them, 11 lncRNAs were found significantly associated with LUAD prognosis in the TCGA database. Two of them (PCBP1-AS1 and ZSCAN16-AS1) were further validated in independent GEO datasets. ScRNA-seq analysis showed that PCBP1-AS1 and ZSCAN16-AS1 were significantly negatively correlated with most of the functional states of LUAD cells, especially with metastasis. Functionally, PCBP1-AS1 was aberrantly downregulated in LUAD cells and tumor tissues. Knockdown of PCBP1-AS1 significantly promoted the migration and invasion of LUAD cells. Consistently, PCBP1-AS1 overexpression suppressed the metastasis of LUAD in vitro and in vivo. Besides, PCBP1-AS1 inhibition induced decreased E-cadherin expression and increased N-cadherin, Vimentin and Snail expression. In conclusion, PCBP1-AS1 could suppress the metastasis of LUAD by targeting the EMT (Epithelial-Mesenchymal Transition) pathway and might serve as a prognostic biomarker and a potential therapeutic target of LUAD.
Biomarkers for Prognosis and Treatment Response in COVID-19 Patients

During a severe infection such as coronavirus disease 2019 (COVID-19), the level of almost all analytes can change, presenting a correlation with disease severity and survival; however, a biomarker cannot be translated into clinical practice for treatment guidance until it is proven to have a significant impact. Several studies have documented the association between COVID-19 severity and circulating levels of C-reactive protein (CRP) and interleukin-6, and the accuracy of the CRP level in predicting treatment responses has been evaluated. Moreover, promising findings on prothrombin and D-dimer have been reported. However, the clinical usefulness of these biomarkers in COVID-19 is far from proven. The burst of data generation during this pandemic has led to the publication of numerous studies with several notable drawbacks, weakening the strength of their findings. We provide an overview of the key findings of studies on biomarkers for the prognosis and treatment response in COVID-19 patients. We also highlight the main drawbacks of these studies that have limited the clinical use of these biomarkers.
Long-term prognosis for patients admitted to a medical intermediate care unit

E-mail: mnmo@ahus.no Medical intermediate care unit Akershus University Hospital Mona Morland has contributed to the idea, design, data collection, analysis and interpretation, literature search, and drafting and revision of the manuscript Mona Morland, specialist in internal medicine and head of unit/senior consultant. The author has completed the ICMJE form and declares no conflicts of interest.
The mechanisms of interest and perseverance in predicting achievement among academically resilient and non-resilient students: Evidence from Swedish longitudinal data.

BACKGROUND Students with low socio-economic status (SES) are typically depicted as low performers and more likely to fail in school. However, a group of students, despite their background, manage to succeed in school. The capacity to overcome adversities and achieve successful educational outcomes is referred to as Academic Resilience. Research on the relationship between personality traits and academic performance shows that conscientiousness is a crucial factor in predicting academic success and resilience. However, it has also been shown that achievement is a result of an interaction between conscientiousness and students' interest in the subject. AIMS The study aims to investigate how students' school-related perseverance and interest predict academic achievement among resilient and non-resilient pupils over time in the Swedish compulsory school setting. SAMPLE Study subjects were a subset (N = 1,665) of the sampled compulsory school students from the 1992 birth cohort in the evaluation through follow-up (ETF) database. METHODS Multigroup structural equation modelling (SEM) with latent variable interaction was used. Measurement invariance was tested to examine the comparability of the constructs across groups. RESULTS The results suggest that resilient students rely heavily on both perseverance of effort and interest in school subjects to succeed in their education. For the non-resilient group, the later perseverance level was conditioned on the level of the interest, and neither their early nor later grade interest was related to their achievement. CONCLUSIONS The academically resilient students displayed more consistency in interest and perseverance over time, which might explain their relative success compared to the non-resilient group.
Identification and evaluation of the inhibitory effect of Prunella vulgaris extract on SARS-coronavirus 2 virus entry

Until now, antiviral therapeutic agents are still urgently required for treatment or prevention of SARS-coronavirus 2 (SCoV-2) virus infection. In this study, we established a sensitive SCoV-2 Spike glycoprotein (SP), including an SP mutant D614G, pseudotyped HIV-1-based vector system and tested their ability to infect ACE2-expressing cells. Based on this system, we have demonstrated that an aqueous extract from the Natural herb Prunella vulgaris (NhPV) displayed potent inhibitory effects on SCoV-2 SP (including SPG614 mutant) pseudotyped virus (SCoV-2-SP-PVs) mediated infections. Moreover, we have compared NhPV with another compound, Suramin, for their anti-SARS-CoV-2 activities and the mode of their actions, and found that both NhPV and Suramin are able to directly interrupt SCoV-2–SP binding to its receptor ACE2 and block the viral entry step. Importantly, the inhibitory effects of NhPV and Suramin were confirmed by the wild type SARS-CoV-2 (hCoV-19/Canada/ON-VIDO-01/2020) virus infection in Vero cells. Furthermore, our results also demonstrated that the combination of NhPV/Suramin with an anti-SARS-CoV-2 neutralizing antibody mediated a more potent blocking effect against SCoV2-SP-PVs. Overall, by using SARS-CoV-2 SP-pseudotyped HIV-1-based entry system, we provide strong evidence that NhPV and Suramin have anti-SARS-CoV-2 activity and may be developed as a novel antiviral approach against SARS-CoV-2 infection.
High-performance cadmium sulphide-based planar perovskite solar cell and the cadmium sulphide/perovskite interfaces

Abstract. Planar heterojunction perovskite solar cell is one of the most competitive photovoltaic technologies, while charge transport materials play a crucial role. We successfully demonstrated an effective electron transport material, namely chemical bath deposited cadmium sulphide (CdS) film under low temperature, in perovskite-based solar cells. Power conversion efficiency of 16.1% has been achieved, which is comparable to that of devices based on TiO2 film prepared via low-temperature processes. Electronic impedance spectra reveal that the CdS-based device presents a higher recombination resistance than TiO2-based devices, which reduces carrier recombination and increases the open circuit voltage. The interface between CdS and perovskite was characterized with improved characteristics when compared to TiO2, e.g., efficient carrier extraction and reduced surface defect–associated degradation in the devices, which help to alleviate anomalous hysteresis and long-term instability. Furthermore, the entire device was fabricated via solution process with a processing temperature below 100°C, suggesting a promising method of further development of perovskite solar cells and commercial manufacturing.
[Relationship between oral Candida albicans and flora in children with severe early childhood caries].

PURPOSE To investigate the relationship between oral Candida albicans and flora in children with severe infant caries. METHODS Forty-two children with severe infant caries (experimental group) and 40 caries-free children (control group) treated in Peking University Shenzhen Hospital from March 2018 to June 2019 were enrolled. The samples of saliva and plaque were collected and cultured. According to the culture results, the experimental group was further divided into two subgroups: Candida albicans positive group and Candida albicans negative group. The samples were sequenced by high-throughput sequencing technology, then the diversity and abundance of bacteria were analyzed. The data were processed by SPSS 23.0 software package. RESULTS The positive rates of Candida albicans in saliva and plaque were significantly higher in the experimental group than in the control group(P<0.05). The abundance of Leptotrichia and Cardiobacterium in the saliva of children with positive Candida albicans in the experimental group was significantly higher than that of children with negative Candida albicans(P<0.05). The abundance of Prevotella in plaque of children with positive Candida albicans in the experimental group was significantly higher than that of children with negative Candida albicans and control group(P<0.05). The abundance of Leptotrichia in saliva of children with positive Candida albicans in the experimental group was significantly higher than that of children with negative Candida albicans (P<0.05), while the abundances of Capnocytophaga, Cardiobacterium hominis, and Capnocytophaga granulose were significantly lower than those of children with negative Candida albicans(P<0.05). The abundance of Streptococcus mutans, Lactobacillus gasseri, and Lactobacillus vaginalis in the plaque of positive Candida albicans in the experimental group were significantly higher than those of children with negative Candida albicans(P<0.05), while the abundance of Lactobacillus plantarum was significantly lower than that of children with negative Candida albicans (P<0.05). CONCLUSIONS Candida albicans in children with severe infant caries children is closely correlated with the abundance of Leptotrichia, Capnocytophaga, Cardiobacterium hominis, Capnocytophaga granulosa, Streptococcus mutans and Lactobacillus, which may play a synergistic or antagonistic role.
Combination of a SARS-CoV-2 IgG Assay and RT-PCR for Improved COVID-19 Diagnosis

Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is generally diagnosed by reverse transcription (RT)-PCR or serological assays. The SARS-CoV-2 viral load decreases a few days after symptom onset. Thus, the RT-PCR sensitivity peaks at three days after symptom onset (approximately 80%). We evaluated the performance of the ARCHITECT® SARS-CoV-2 IgG assay (henceforth termed IgG assay; Abbott Laboratories, Lake County, IL, USA), and the combination of RT-PCR and the IgG assay for COVID-19 diagnosis. Methods In this retrospective study, 206 samples from 70 COVID-19 cases at two hospitals in Tokyo that were positive using RT-PCR were used to analyze the diagnostic sensitivity. RT-PCR-negative (N=166), COVID-19-unrelated (N=418), and Japanese Red Cross Society (N=100) samples were used to evaluate specificity. Results Sensitivity increased daily after symptom onset and exceeded 84.4% after 10 days. Specificity ranged from 98.2% to 100% for samples from the three case groups. Seroconversion was confirmed from 9 to 20 days after symptom onset in 18 out of 32 COVID-19 cases with multiple samples and from another case with a positive result in the IgG assay for the first available sample. Conclusions The combination of RT-PCR and IgG assay improves the robustness of laboratory diagnostics by compensating for the limitations of each method.