Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical and financial burden of hospitalised community-acquired pneumonia in patients with selected underlying comorbidities in England

Background Hospitalised pneumonia may have long-term clinical and financial impact in adult patients with underlying comorbidities. Methods We conducted a retrospective cohort study using the Hospital Episode Statistics (HES) database to determine the clinical and financial burden over 3 years of hospitalised community-acquired pneumonia (CAP) to England’s National Health Service (NHS). Subjects were adults with six underlying comorbidities (chronic heart disease (CHD); chronic kidney disease (CKD); chronic liver disease (CLD); chronic respiratory disease (CRD); diabetes mellitus (DM) and post bone marrow transplant (post-BMT)) with an inpatient admission in 2012/2013. Patients with CAP in 2013/2014 were followed for 3 years and compared with similarly aged, propensity score-matched adults with the same comorbidity without CAP. Findings The RR of hospital admissions increased after CAP, ranging from 1.08 (95% CI 1.04 to 1.12) for CKD to 1.38 (95% CI 1.35 to 1.40) for CRD. This increase was maintained for at least 2 years. Mean difference in hospital healthcare costs (£) was higher for CAP patients in 2013/2014; ranging from £1115 for DM to £8444 for BMT, and remained higher for 4/6 groups for 2 more years, ranging from £1907 (95% CI £1573 to £2240) for DM to £11 167 (95% CI £10 847 to £11 486) for CRD. ) The OR for mortality was significantly higher for at least 3 years after CAP, ranging from 4.76 (95% CI 4.12 to 5.51, p<0.0001) for CLD to 7.50 (95%CI 4.71 to 11.92, p<0.0001) for BMT. Interpretation For patients with selected underlying comorbidities, healthcare utilisation, costs and mortality increase for at least 3 years after being hospitalised CAP.
Aberrant expression of NKL homeobox genes HMX2 and HMX3 interferes with cell differentiation in acute myeloid leukemia

The NKL-code describes normal expression patterns of NKL homeobox genes in hematopoiesis. Aberrant expression of NKL homeobox gene subclass members have been reported in several hematopoietic malignancies including acute myeloid leukemia (AML). Here, we analyzed the oncogenic role of the HMX-group of NKL homeobox genes in AML. Public expression profiling data–available for HMX1 and HMX2—indicate aberrant activity of HMX2 in circa 2% AML patients overall, rising to 31% in those with KMT2A/MLL rearrangements whereas HMX1 expression remains inconspicuous. AML cell lines EOL-1, MV4-11 and MOLM-13 expressed both, HMX2 and neighboring HMX3 genes, and harbored KMT2A aberrations, suggesting their potential functional association. Surprisingly, knockdown experiments in these cell lines demonstrated that KMT2A inhibited HMX2/3 which, in turn, did not regulate KMT2A expression. Furthermore, karyotyping and genomic profiling analysis excluded rearrangements of the HMX2/3 locus in these cell lines. However, comparative expression profiling and subsequent functional analyses revealed that IRF8, IL7- and WNT-signalling activated HMX2/3 expression while TNFa/NFkB- signalling proved inhibitory. Whole genome sequencing of EOL-1 identified two mutations in the regulatory upstream regions of HMX2/3 resulting in generation of a consensus ETS-site and transformation of a former NFkB-site into an SP1-site. Reporter-gene assays demonstrated that both mutations contributed to HMX2/3 activation, modifying ETS1/ELK1- and TNFalpha-mediated gene regulation. Moreover, DMSO-induced eosinophilic differentiation of EOL-1 cells coincided with HMX2/3 downregulation while knockdown of HMX2 induced cell differentiation, collectively supporting a fundamental role for these genes in myeloid differentiation arrest. Finally, target genes of HMX2/3 were identified in EOL-1 and included suppression of differentiation gene EPX, and activation of fusion gene FIP1L1-PDGFRA and receptor-encoding gene HTR7, both of which enhanced oncogenic ERK-signalling. Taken together, our study documents a leukemic role for deregulated NKL homeobox genes HMX2 and HMX3 in AML, revealing molecular mechanisms of myeloid differentiation arrest.
Shared Neural Representations of Cognitive Conflict and Negative Affect in the Medial Frontal Cortex

Influential theories of Medial Frontal Cortex (MFC) function suggest that the MFC registers cognitive conflict as an aversive signal, but no study directly tested this idea. Instead, recent studies suggested that nonoverlapping regions in the MFC process conflict and affect. In this preregistered human fMRI study (male and female), we used MVPAs to identify which regions respond similarly to conflict and aversive signals. The results reveal that, of all conflict- and value-related regions, only the ventral pre-supplementary motor area (or dorsal anterior cingulate cortex) showed a shared neural pattern response to different conflict and affect tasks. These findings challenge recent conclusions that conflict and affect are processed independently, and provide support for integrative views of MFC function. SIGNIFICANCE STATEMENT Multiple theories propose that the MFC, and the dorsal ACC in particular, integrates information related to suboptimal outcomes from different psychological domains (e.g., cognitive control and negative affect) with the aim of adaptively steering behavior. In contrast to recent studies in the field, we provide evidence for the idea that cognitive control and negative affect are integrated in the MFC by showing that a classification algorithm trained on discerning cognitive control (conflict vs no conflict) can predict affect (negative vs positive) in the voxel pattern response of the dorsal ACC/pre-SMA.
Study of the Activity of Two Antioxidant Enzymes of Spirulina maxima Under Excessive Light Stress

The changes of activities of two antioxidant enzymes of Spirulina maxima 438 was surveyed under excessive light stress. They were superoxide dismutase (SOD) and catalase (CAT). The authors found that the activities of the two enzymes changed under excessive light stress. Under excessive light stress, the activity of SOD rose up at the first and was above the activity of SOD under normal conditions. Then, the activity of SOD dropped down. Through the isoenzyme electrophoresis, a new kind of isoenzyme was inducted and the expression quantity of the enzymes was increased also. The activity of catalase dropped notably first, then rose up slightly. But the activity of catalase under excessive light stress was below the activity of catalase under normal conditions all the time.
Socio‐economic status, executive functions, and theory of mind ability in adolescents: Relationships with language ability and cortisol

Socio‐economic status (SES) is linked to the development of cognitive abilities, particularly language and executive processes. It is unclear whether these represent a single or independent correlates. We studied 110 Ecuadorian youths aged 12–17 with measures of SES, language, executive function, and theory of mind (ToM), a.k. a. mentalizing. A subsample gave hair samples to estimate recent cortisol levels. Restricting analyses to reliable measures, SES was highly associated with language skill, and to a lesser extent with executive function and ToM performance. However, those latter associations were attenuated and non‐significant when language ability was controlled for statistically. Systemic cortisol levels were not associated with SES, but were significantly and negatively correlated with ToM, independent of variation in language skills. We conclude that language development underlies most of the impact of SES on executive function and ToM ability of adolescents, but that stress‐related cortisol may have an independent, direct effect on mentalizing.
Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation

Simple Summary Uveal melanoma is a rare but deadly cancer that shows remarkable metastatic tropism to the liver. Extracellular vesicles (EVs) are nanometer-sized, lipid bilayer-membraned particles that are released from cells. In our study we used EVs derived from primary normal choroidal melanocytes and matched primary and metastatic uveal melanoma cell lines from a patient. Analysis of these EVs revealed important protein signatures that may be involved in tumorigenesis and metastatic dissemination. We have established a model to study EV functions and phenotypes which can be used in EV-based liquid biopsy. Abstract Extracellular vesicles (EVs) carry molecules derived from donor cells and are able to alter the properties of recipient cells. They are important players during the genesis and progression of tumors. Uveal melanoma (UM) is the most common primary intraocular tumor in adults and is associated with a high rate of metastasis, primarily to the liver. However, the mechanisms underlying this process are poorly understood. In the present study, we analyzed the oncogenic potential of UM-derived EVs and their protein signature. We isolated and characterized EVs from five UM cell lines and from normal choroidal melanocytes (NCMs). BRCA1-deficient fibroblasts (Fibro-BKO) were exposed to the EVs and analyzed for their growth in vitro and their reprograming potential in vivo following inoculation into NOD-SCID mice. Mass spectrometry of proteins from UM-EVs and NCM-EVs was performed to determine a protein signature that could elucidate potential key players in UM progression. In-depth analyses showed the presence of exosomal markers, and proteins involved in cell-cell and focal adhesion, endocytosis, and PI3K-Akt signaling pathway. Notably, we observed high expression levels of HSP90, HSP70 and integrin V in UM-EVs. Our data bring new evidence on the involvement of UM-EVs in cancer progression and metastasis.
Towards Accurate Genotype–Phenotype Correlations in the CYP2D6 Gene

Establishing accurate and large-scale genotype–phenotype correlations and predictions of individual response to pharmacological treatments are two of the holy grails of Personalized Medicine. These tasks are challenging and require an integrated knowledge of the complex processes that regulate gene expression and, ultimately, protein functionality in vivo, the effects of mutations/polymorphisms and the different sources of interindividual phenotypic variability. A remarkable example of our advances in these challenging tasks is the highly polymorphic CYP2D6 gene, which encodes a cytochrome P450 enzyme involved in the metabolization of many of the most marketed drugs (including SARS-Cov-2 therapies such as hydroxychloroquine). Since the introduction of simple activity scores (AS) over 10 years ago, its ability to establish genotype–phenotype correlations on the drug metabolizing capacity of this enzyme in human population has provided lessons that will help to improve this type of score for this, and likely many other human genes and proteins. Multidisciplinary research emerges as the best approach to incorporate additional concepts to refine and improve such functional/activity scores for the CYP2D6 gene, as well as for many other human genes associated with simple and complex genetic diseases.
Findings and lessons learnt from early termination of a pragmatic comparative effectiveness trial of video consultations in home-based palliative care

Background Health systems need evidence about how best to deliver home-based palliative care (HBPC) to meet the growing needs of seriously ill patients. We hypothesised that a tech-supported model that aimed to promote timely inter-professional team coordination using video consultation with a remote physician while a nurse is in the patient’s home would be non-inferior compared with a standard model that includes routine home visits by nurses and physicians. Methods We conducted a pragmatic, cluster randomised non-inferiority trial across 14 sites (HomePal Study). Registered nurses (n=111) were randomised to the two models so that approximately half of the patients with any serious illness admitted to HBPC and their caregivers were enrolled in each study arm. Process measures (video and home visits and satisfaction) were tracked. The primary outcomes for patients and caregivers were symptom burden and caregiving preparedness at 1–2 months. Results The study was stopped early after 12 months of enrolment (patients=3533; caregivers=463) due to a combination of low video visit uptake (31%), limited substitution of video for home visits, and the health system’s decision to expand telehealth use in response to changes in telehealth payment policies, the latter of which was incompatible with the randomised design. Implementation barriers included persistent workforce shortages and inadequate systems that contributed to scheduling and coordination challenges and unreliable technology and connectivity. Conclusions We encountered multiple challenges to feasibility, relevance and value of conducting large, multiyear pragmatic randomised trials with seriously ill patients in the real-world settings where care delivery, regulatory and payment policies are constantly shifting.
Tracking SARS-CoV-2 in Sewage: Evidence of Changes in Virus Variant Predominance during COVID-19 Pandemic

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), responsible for the ongoing coronavirus disease (COVID-19) pandemic, is frequently shed in faeces during infection, and viral RNA has recently been detected in sewage in some countries. We have investigated the presence of SARS-CoV-2 RNA in wastewater samples from South-East England between 14th January and 12th May 2020. A novel nested RT-PCR approach targeting five different regions of the viral genome improved the sensitivity of RT-qPCR assays and generated nucleotide sequences at sites with known sequence polymorphisms among SARS-CoV-2 isolates. We were able to detect co-circulating virus variants, some specifically prevalent in England, and to identify changes in viral RNA sequences with time consistent with the recently reported increasing global dominance of Spike protein G614 pandemic variant. Low levels of viral RNA were detected in a sample from 11th February, 3 days before the first case was reported in the sewage plant catchment area. SARS-CoV-2 RNA concentration increased in March and April, and a sharp reduction was observed in May, showing the effects of lockdown measures. We conclude that viral RNA sequences found in sewage closely resemble those from clinical samples and that environmental surveillance can be used to monitor SARS-CoV-2 transmission, tracing virus variants and detecting virus importations.
Effects of Various Nitrogen Applications on the Quality of the Progeny Seedlings in Rice

To explore the effects of nitrogen application on the protein content of rice seeds and the quality of its progeny seedlings, water culture was carried out and the physiological activities of the progeny seedlings in 5—13 days after the germination of the harvested seeds of the two common rice cultivars (japonica and indica) were measured. The rice plant was treated with various nitrogen applications at booting and tillering stages respectively. The principal results are as follows: (1) The protein content in caryopsis was the highest in the treatment with the higher application of nitrogen at booting stage than that at the tillering stage. (2)The increment of nitrogen application at booting stage had the positive effects on the height, fresh and dry weight of the seedlings, the chlorophyll content of the leaves, the photosynthetic rate, the content of soluble protein, the IAA content, amylase activities of the endosperm, the activities of CAT in leaves, and SOD in root tips. Meanwhile, their chilling resistance was enhanced compared with the seedlings without nitrogen supply. (3) The soluble sugar content was the highest in the seedlings with no nitrogen application, and the lowest in those with higher application of nitrogen at booting stage. So, the proper increase of nitrogen application at booting stage could be favorable to the growth of rice seedlings as well as the protein content in caryopsis.
LncRNA Platr22 promotes super-enhancer activity and stem cell pluripotency

Abstract Super-enhancers (SEs) comprise large clusters of enhancers, which are co-occupied by multiple lineage-specific and master transcription factors, and play pivotal roles in regulating gene expression and cell fate determination. However, it is still largely unknown whether and how SEs are regulated by the noncoding portion of the genome. Here, through genome-wide analysis, we found that long noncoding RNA (lncRNA) genes preferentially lie next to SEs. In mouse embryonic stem cells (mESCs), depletion of SE-associated lncRNA transcripts dysregulated the activity of their nearby SEs. Specifically, we revealed a critical regulatory role of the lncRNA gene Platr22 in modulating the activity of a nearby SE and the expression of the nearby pluripotency regulator ZFP281. Through these regulatory events, Platr22 contributes to pluripotency maintenance and proper differentiation of mESCs. Mechanistically, Platr22 transcripts coat chromatin near the SE region and interact with DDX5 and hnRNP-L. DDX5 further recruits p300 and other factors related to active transcription. We propose that these factors assemble into a transcription hub, thus promoting an open and active epigenetic chromatin state. Our study highlights an unanticipated role for a class of lncRNAs in epigenetically controlling the activity and vulnerability to perturbation of nearby SEs for cell fate determination.
An Efficient Approach to Identify Salt Tolerance of Upland Cotton at Seedling Stage

Three-leaf cotton seedlings of two salt-tolerant varieties and two salt-sensitive varieties were treated by water and 4%(40 g L–1) NaCl solution, respectively. A total of 13 parameters related to salt tolerance including salt injury index(SII), shoot fresh weight(SRW), root fresh weight(RFW), leaf relative water content(RWC), chlorophyll fluorescence parameters(Fo, Fm, Fv/Fm), relative conductivity(RC), manlondialdehyde(MDA) content and the activity of antioxidant enzymes were monitored after 72 h of treatment. Comprehensive assessment of salinity tolerance based on grey relation clustering method, principal component analysis and stepwise regression analysis indicated that the maximum quantum yield of PSII was the most significant correlated indices with salt tolerance in upland cotton, which could be used as a single parameter to assess salt tolerance based on the equation: y = 1.943x – 0.882(where y is the salt tolerance index, x is the related value of maximum efficiency of photosystem II). The other two salt-tolerant varieties and two salt-sensitive varieties were used to rate the classification of salt tolerance. Salt tolerance index(y) of 23 varieties with known salt tolerance were calculated to validate the accuracy of the equation, the result was consistent with field investigation. In this study, the maximum efficiency of photosystem II was used as the main index to validate the salt tolerance in cotton, together with the construction of salt tolerance index equation and salt tolerance rating, which could greatly improve the efficiency of salinity tolerance evaluation for massive germplasm in future.
Diversity Analysis and Associated Antimicrobial Activity of Essential Oil in Pyrrosia petiolosa

The continued development of folk medicine to potentially treat infectious diseases has resulted in an increase in natural sources of antimicrobial agents, particularly the use of plant essential oils containing volatile products from secondary metabolism. The objectives of this investigation were to (i) analyze the chemical components of essential oils using GC/MS and (ii) to examine their in vitro antimicrobial activities against four strains of bacteria (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Shigella flexneri) and one fungus (Candida albicans) by determining minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) in liquid and solid media, respectively, from different Pyrrosia petiolosa locations. Eighty‐eight evaporable compounds were confirmed in their essential oils; the major components in the oils were 2,4‐pentadienal (12.5 %), phytol (10.5 %) and nonanal (8.6 %). Based on hierarchical cluster analysis, Pyrrosia samples were categorized into four groups, indicating significant essential oil diversity from different Pyrrosia locations. Results also indicated that essential oils had a broad spectrum of antibacterial activities, particularly against Shigella flexneri and Staphylococcus aureus with MICs of 5 μL/mL. Results from this investigation are the first to record the chemical component and antimicrobial potential of essential oils from different P. Petiolosa locations.
Production of ROS by Gallic Acid Activates KDM2A to Reduce rRNA Transcription

Metformin, which is suggested to have anti-cancer effects, activates KDM2A to reduce rRNA transcription and proliferation of cancer cells. Thus, the specific activation of KDM2A may be applicable to the treatment of cancers. In this study, we screened a food-additive compound library to identify compounds that control cell proliferation. We found that gallic acid activated KDM2A to reduce rRNA transcription and cell proliferation in breast cancer MCF-7 cells. Gallic acid accelerated ROS production and activated AMPK. When ROS production or AMPK activity was inhibited, gallic acid did not activate KDM2A. These results suggest that both ROS production and AMPK activation are required for activation of KDM2A by gallic acid. Gallic acid did not reduce the succinate level, which was required for KDM2A activation by metformin. Metformin did not elevate ROS production. These results suggest that the activation of KDM2A by gallic acid includes mechanisms distinct from those by metformin. Therefore, signals from multiple intracellular conditions converge in KDM2A to control rRNA transcription. Gallic acid did not induce KDM2A-dependent anti-proliferation activity in non-tumorigenic MCF10A cells. These results suggest that the mechanism of KDM2A activation by gallic acid may be applicable to the treatment of breast cancers.
Comparative Study of Pd/B4C X-ray Multilayer Mirrors Fabricated by Magnetron Sputtering with Kr and Ar Gas

Ultrathin Pd/B4C multilayers are suitable X-ray mirrors working at the photon energy region of 7–20 keV. To further improve the layer structure, Pd/B4C multilayers with a d-spacing of 2.5 nm were fabricated by magnetron sputtering using the heavy noble gas Kr and compared with the conventional ones fabricated by Ar. Although the Kr-sputtering process can work at a lower pressure, the interface width—especially the interface roughness—is a little larger than that made by Ar. A stronger polycrystallization and a lower content of sputter gas atoms were found in the Kr-made sample, which can be explained by the joint effect from less recoiled particles and lower sputtering pressure. A good reflectance of 68% of the Kr made multilayer was measured at 10 keV, which is only slightly lower than that of the Ar made sample (71%).
STUDIES IN MESPILUS , CRATAEGUS , AND × CRATAEMESPILUS (ROSACEAE), I. DIFFERENTIATION OF MESPILUS AND CRATAEGUS , EXPANSION OF × CRATAEMESPILUS , WITH SUPPLEMENTARY OBSERVATIONS ON DIFFERENCES BETWEEN THE CRATAEGUS AND AMELANCHIER CLADES

The paper argues the position for retaining a monotypic Mespilus , i.e., in the sense of M. germanica , the medlar. Recent cladistic papers lend support for Mespilus being sister to Crataegus , and there is a clear morphological distinction from Crataegus , emphasized by adaptation to carnivore frugivory. Mespilus secured, the paper then treats each of the known hybrids between Mespilus and Crataegus , making the new combination Crataemespilus ×canescens (J.B. Phipps) J.B. Phipps.