Miracle-dz/UniFAR-FTUs huggingface dataset:
Long term use of benzodiazepines by patients cared for by primary care physicians in consultation with psychiatrists

Benzodiazepines (BDZ) continue to be among the most widely prescribed medications. Recommended use of benzodiazepines is typically for short-term treatment. In the real-world practice, long-term use of benzodiazepines is reported however, with a prevalence varying from 2% to 3.5% in the general population and 30%–55% among the total users of benzodiazepines. A nation-wide study in Australia showed an increasing rate of long-term benzodiazepine prescription in the general practice. Most studies of the long-term benzodiazepines use were based on registry data; direct assessments of patients' use have been a few. A sizable proportion of patients receive benzodiazepines from their General Practitioners (GP) or primary care physicians. Participants for this study were selected from a consecutive sample of patients referred to a single specialist psychiatry practice by their general practitioners (GPs). For the present study, treatment with one or more benzodiazepines for a minimum period of 2 years and age above 18 years were the inclusion criteria. We chose the use of more than 2 years because previous studies followed up benzodiazepine users for 2–2.5 years and there is little information on the use beyond 2 years. Potential participants were identified from the medical records that were screened for the period 2017–2020. Although the records were screened for referrals during 2017–2020, participants could have received a benzodiazepine any time prior to this period. Investigators of this study mailed out the participant information and consent forms along with the questionnaire to the potential participants. The benzodiazepine dependence self-report questionnaire (Bendep SRQ) short version (SV) was used to screen for benzodiazepine use in the past 6 months. The Bendep SRQ (SV) is a self-rated instrument that elicits responses on four key aspects of use: problematic use, preoccupation with the use, lack of compliance with prescriptions, and withdrawal symptoms. The study identified 30 eligible patients who were contacted after receiving approval from the Human Research Ethics Committee of Goulburn valley health. The results are summarised in the Table 1. Altogether, 17 patients responded with consent to participate. The mean age of the responders was 62 years. There were 14 female participants and three male participants. All of them, except one, were current users of a benzodiazepine. Alprazolam was the commonest benzodiazepine. All except one participant were taking a single benzodiazepine. One participant was using a combination of diazepam (15 mg daily dose) and clonazepam (0.5 mg). The duration of benzodiazepine use prior to this study Previous publication or presentation of the information contained in this manuscript: None. Received: 9 January 2022 Revised: 19 April 2022 Accepted: 20 April 2022
Circular RNA circRNA-0039459 promotes the migration, invasion, and proliferation of liver cancer cells through the adsorption of miR-432

ABSTRACT This study aimed to investigate the molecular mechanism of circular RNA circ-0039459 and its effects on the apoptosis, proliferation, invasion, and migration of hepatocellular carcinoma cells. The expression of circ-0039459, miR-432, and synoviolin 1 (SYVN1) mRNA was determined using real-time quantitative reverse transcription PCR. Cell proliferation was detected by cell counting kit-8 assay, and the apoptosis rate was detected using flow cytometry. Cell migration and invasion were detected using Transwell assay. The expression of E-cadherin, N-cadherin, and vimentin was detected using western blot. The targeting relationship between circ-0039459 and miR-432 as well as that between miR-432 and SYVN1 were detected using the dual-luciferase reporter and RNA pull-down assays. We found that circ-0039459 and SYVN1 mRNA were highly expressed, whereas miR-432 was lowly expressed in hepatocellular carcinoma cells and tissues. After treatment with ribonuclease R or actinomycin D, the expression of linear RNA was reduced, whereas that of circular RNA was not significantly changed. circ-0039459 knockdown or miR-432 overexpression can inhibit cell proliferation, invasion, and migration and the expression of N-cadherin and vimentin proteins in carcinoma cells as well as promote apoptosis and increase the E-cadherin level. circ-0039459 targeted and regulated miR-432, which targeted and regulated SYVN1. The decreased miR-432 expression reversed the effects of circ-0039459 knockout in cancer cells. Furthermore, SYVN1 overexpression reversed the effect of miR-432 overexpression in hepatoma cells. Hence, circ-0039459 can affect the proliferation, apoptosis, migration, and invasion of hepatocellular carcinoma cells through the adsorption of miR-432, thereby regulating the expression of SYVN1. Graphical Abstract
A new perspective when examining maize fertilizer nitrogen use efficiency, incrementally

For maize (Zea mays L.), nitrogen (N) fertilizer use is often summarized from field to global scales using average N use efficiency (NUE). But expressing NUE as averages is misleading because grain increase to added N diminishes near optimal yield. Thus, environmental risks increase as economic benefits decrease. Here, we use empirical datasets obtained in North America of maize grain yield response to N fertilizer (n = 189) to create and interpret incremental NUE (iNUE), or the change in NUE with change in N fertilization. We show for those last units of N applied to reach economic optimal N rate (EONR) iNUE for N removed with the grain is only about 6%. Conversely stated, for those last units of N applied over 90% is either lost to the environment during the growing season, remains as inorganic soil N that too may be lost after the growing season, or has been captured within maize stover and roots or soil organic matter pools. Results also showed iNUE decrease averaged 0.63% for medium-textured soils and 0.37% for fine-textured soils, attributable to fine-textured soils being more predisposed to denitrification and/or lower mineralization. Further analysis demonstrated the critical nature growing season water amount and distribution has on iNUE. Conditions with too much rainfall and/or uneven rainfall produced low iNUE. Producers realize this from experience, and it is uncertain weather that largely drives insurance fertilizer additions. Nitrogen fertilization creating low iNUE is environmentally problematic. Our results show that with modest sub-EONR fertilization and minor forgone profit, average NUE improvements of ~10% can be realized. Further, examining iNUE creates unique perspective and ideas for how to improve N fertilizer management tools, educational programs, and public policies and regulations.
Subclinical giant cell arteritis in new onset polymyalgia rheumatica A systematic review and meta-analysis of individual patient data.

OBJECTIVES To determine the prevalence and predictors of subclinical giant cell arteritis (GCA) in patients with newly diagnosed polymyalgia rheumatica (PMR). METHODS PubMed, Embase, and Web of Science Core Collection were systematically searched (date of last search July 14, 2021) for any published information on any consecutively recruited cohort reporting the prevalence of GCA in steroid-naïve patients with PMR without cranial or ischemic symptoms. We combined prevalences across populations in a random-effect meta-analysis. Potential predictors of subclinical GCA were identified by mixed-effect logistic regression using individual patient data (IPD) from cohorts screened with PET/(CT). RESULTS We included 13 cohorts with 566 patients from studies published between 1965 to 2020. Subclinical GCA was diagnosed by temporal artery biopsy in three studies, ultrasound in three studies, and PET/(CT) in seven studies. The pooled prevalence of subclinical GCA across all studies was 23% (95% CI 14%-36%, I2=84%) for any screening method and 29% in the studies using PET/(CT) (95% CI 13%-53%, I2=85%) (n=266 patients). For seven cohorts we obtained IPD for 243 patients screened with PET/(CT). Inflammatory back pain (OR 2.73, 1.32-5.64), absence of lower limb pain (OR 2.35, 1.05-5.26), female sex (OR 2.31, 1.17-4.58), temperature >37° (OR 1.83, 0.90-3.71), weight loss (OR 1.83, 0.96-3.51), thrombocyte count (OR 1.51, 1.05-2.18), and haemoglobin level (OR 0.80, 0.64-1.00) were most strongly associated with subclinical GCA in the univariable analysis but not C-reactive protein (OR 1.00, 1.00-1.01) or erythrocyte sedimentation rate (OR 1.01, 1.00-1.02). A prediction model calculated from these variables had an area under the curve of 0.66 (95% CI 0.55-0.75). CONCLUSION More than a quarter of patients with PMR may have subclinical GCA. The prediction model from the most extensive IPD set has only modest diagnostic accuracy. Hence, a paradigm shift in the assessment of PMR patients in favour of implementing imaging studies should be discussed.
Canadian and Brazilian Percentile Ranks for the Alberta Infant Motor Scale

Abstract Aim: To verify if there is a difference between the percentile ranks for Brazilian infants compared with norms for Canadian infants on the Alberta Infant Motor Scale (AIMS). Method: A cross-sectional study in which 322 Brazilian infants, 2 to 15 months old, were administered the AIMS. Percentile ranks were calculated using norms for Canadian infants and norms from two studies of Brazilian infants. The Friedman test compared the AIMS percentile ranks for the entire sample. For reliability analysis, the interclass correlation coefficient (ICC) was used. Bland Altman's analysis was applied to compare percentile ranks. Results: Of the 322 evaluations analyzed, there were significant differences (p<.001) between the three percentile ranks compared. The Canadian norms presented the lowest average rating. There was good reliability between the percentile ranks (ICC > 0.75) but low agreement (Bland Altman; p<.001). Conclusion: There are differences between the Brazilian and Canadian percentile ranks and between the Brazilian percentile ranks of 2014 and 2016, and these differences may influence identification of motor development.
The flexible N-terminal motif of uL11 unique to eukaryotic ribosomes interacts with P-complex and facilitates protein translation

Abstract Eukaryotic uL11 contains a conserved MPPKFDP motif at the N-terminus that is not found in archaeal and bacterial homologs. Here, we determined the solution structure of human uL11 by NMR spectroscopy and characterized its backbone dynamics by 15N–1H relaxation experiments. We showed that these N-terminal residues are unstructured and flexible. Structural comparison with ribosome-bound uL11 suggests that the linker region between the N-terminal domain and C-terminal domain of human uL11 is intrinsically disordered and only becomes structured when bound to the ribosomes. Mutagenesis studies show that the N-terminal conserved MPPKFDP motif is involved in interacting with the P-complex and its extended protuberant domain of uL10 in vitro. Truncation of the MPPKFDP motif also reduced the poly-phenylalanine synthesis in both hybrid ribosome and yeast mutagenesis studies. In addition, G→A/P substitutions to the conserved GPLG motif of helix-1 reduced poly-phenylalanine synthesis to 9–32% in yeast ribosomes. We propose that the flexible N-terminal residues of uL11, which could extend up to ∼25 Å from the N-terminal domain of uL11, can form transient interactions with the uL10 that help to fetch and fix it into a position ready for recruiting the incoming translation factors and facilitate protein synthesis.
Incidence of post-stroke depression symptoms and potential risk factors in adults with aphasia in a comprehensive stroke center

ABSTRACT Introduction Depression may be a frequent sequela after stroke, however, its incidence has rarely been reported. The likelihood of post-stroke depression (PSD) may relate to individual factors including the presence of aphasia, which also complicates PSD diagnosis. The current study’s purpose was to investigate the incidence of PSD symptoms in adults with aphasia, compare it to the incidence of PSD symptoms in adults without aphasia, and to identify potential risk factors for developing PSD in adults with aphasia. Method Incidence proportions and relative risk were calculated using data compiled from 970 patient records at an urban tertiary care academic institution and comprehensive stroke center throughout the year of 2019. Focusing exclusively on adults with aphasia, the selected variables of age, gender, race, and aphasia severity were used to conduct logistic regression analyses to explore potential risk factors contributing to the development of PSD. Results Adults with aphasia were 7.408 times more likely to exhibit PSD symptoms than adults without aphasia. Logistic regression controlling for the presence of aphasia showed a significant relationship between aphasia severity and post-stroke depression symptoms. Adults with aphasia were 2.06 times more likely to experience post-stroke depression symptoms with every 1-point increase in aphasia severity. Conclusions These findings align with earlier evidence identifying aphasia as a risk factor for experiencing PSD symptoms and also suggest aphasia severity is proportionate to the risk. This highlights the need for early identification of PSD symptoms in persons with aphasia in order to provide timely interventions.
A PLETHORA/PIN-FORMED/auxin network mediates prehaustorium formation in the parasitic plant Striga hermonthica

Abstract The parasitic plant Striga (Striga hermonthica) invades the host root through the formation of a haustorium and has detrimental impacts on cereal crops. The haustorium results from the prehaustorium, which is derived directly from the differentiation of the Striga radicle. The molecular mechanisms leading to radicle differentiation shortly after germination remain unclear. In this study, we determined the developmental programs that regulate terminal prehaustorium formation in S. hermonthica at cellular resolution. We showed that shortly after germination, cells in the root meristem undergo multiplanar divisions. During growth, the meristematic activity declines and associates with reduced expression of the stem cell regulator PLETHORA1 and the cell cycle genes CYCLINB1 and HISTONE H4. We also observed a basal localization of the PIN-FORMED (PIN) proteins and a decrease in auxin levels in the meristem. Using the structural layout of the root meristem and the polarity of outer-membrane PIN proteins, we constructed a mathematical model of auxin transport that explains the auxin distribution patterns observed during S. hermonthica root growth. Our results reveal a fundamental molecular and cellular framework governing the switch of S. hermonthica roots to form the invasive prehaustoria.
Trends in Inuit health services utilisation in Manitoba: findings from the Qanuinngitsiarutiksait study

ABSTRACT There is a notable lack of research related to trends in Inuit accessing health services throughout the land known as Canada. Given Nunavut’s reliance on specialised services provided in the Northwest Territories, Alberta, Manitoba, and Ontario, this gap is particularly problematic, making it more difficult for Nunangat to proactively plan new programs for emerging needs, and for provinces to respond to those needs. The Qanuinngitsiarutiksait study aimed to address this gap by developing detailed profiles of Inuit accessing health services in Manitoba. We used administrative data routinely collected by Manitoba agencies, to support the development of Inuit-centric services. It was conducted in partnership with the Manitoba Inuit Association, and Inuit Elders from Nunavut Canada and Manitoba. We focused on two interrelated cohorts: Kivallirmiut (Inuit from the Kivalliq region of Nunavut) who come to Winnipeg to access specialised services; and Manitobamiut (Inuit already living in Manitoba). Findings show that health services are primarily accessed in Winnipeg. Half of health services accessed by Kivallirmiut are for in-patient care at facilities with the Winnipeg Regional Health Authority. The other half are for advanced out-patient care including specialist consults. For Kivallirmiut, hospitalisation for pregnancy and birth are the most prevalent reasons for hospitalisation, followed by diseases of the respiratory system. Noteworthy, rates of hospitalisation for conditions treatable in primary healthcare for Kivallirmiut are considerably lower than those for Manitobans living in the northern part of the province (where comparable constraints exist). For Inuit adults, rates of hospitalisation for these conditions are comparable to those of Manitobans living in small communities. Inuit living in Manitoba are most often hospitalised for mental health reasons, although other reasons are nearly as prevalent. Our results support the need for more Inuit-centric health programming in Winnipeg.
Crude metabolites from endophytic fungi inhabiting Cameroonian Annona muricata inhibit the causative agents of urinary tract infections

Urinary tract infections (UTIs) are common bacterial infections. The global emergence of multidrug-resistant uropathogens in the last decade underlines the need to search for new antibiotics with novel mechanisms of action. In this regard, exploring endophytic fungi inhabiting medicinal plants used locally against urinary tract infections could be a promising strategy for novel drug discovery. This study investigates crude metabolites from endophytic fungi isolated from Annona muricata as potential sources of antibiotic drugs to fight against uropathogens and reduce related oxidative stress. Crude ethyl acetate extracts from 41 different endophytic fungi were screened against three bacterial strains using the broth microdilution method, and fungi producing active crude extracts were identified using ITS1-5.8S rRNA-ITS2 nucleotide sequences. The antibacterial modes of action of the five most active extracts were evaluated using Staphylococcus aureus ATCC 43300 and Klebsiella oxytoca strains. The DPPH and FRAP assays were used to investigate their antioxidant activity, and their cytotoxicity against the Vero cell line was evaluated using the MTT assay. Out of the 41 crude extracts tested, 17 were active with minimum inhibitory concentrations (MICs) ranging from 3.125 μg/mL to 100 μg/mL and were not cytotoxic against Vero cell lines with a cytotoxic concentration 50 (CC50) >100 μg/mL. The more potent extracts (from Fusarium waltergamsii AMtw3, Aspergillus sp. AMtf15, Penicillium citrinum AMf6, Curvularia sp. AMf4, and Talaromyces annesophieae AMsb23) significantly inhibited bacterial catalase activity, lysed bacterial cells, increased outer membrane permeability, and inhibited biofilm formation, and the time-kill kinetic assay revealed concentration-dependent bactericidal activity. All seventeen extracts showed weak ferric iron-reducing power (1.06 to 12.37 μg equivalent NH2OH/g of extract). In comparison, seven extracts exhibited DPPH free radical scavenging activity, with RSA50 ranging from 146.05 to 799.75 μg/mL. The molecular identification of the seventeen active fungi revealed that they belong to six distinct genera, including Aspergillus, Curvularia, Fusarium, Meyerozyma, Penicillium, and Talaromyces. This investigation demonstrated that fungal endophytes from Cameroonian Annona muricata, a medicinal plant used locally to treat bacterial infections, might contain potent antibacterial metabolites with multiple modes of action. The antibacterial-guided fractionation of these active extracts is currently ongoing to purify and characterise potential antibacterial active ingredients.
Virological and Serological Assessment of US Army Trainees Isolated for Coronavirus Disease 2019

Abstract Background Laboratory screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key mitigation measure to avoid the spread of infection among recruits starting basic combat training in a congregate setting. Because viral nucleic acid can be detected persistently after recovery, we evaluated other laboratory markers to distinguish recruits who could proceed with training from those who were infected. Methods Recruits isolated for coronavirus disease 2019 (COVID-19) were serially tested for SARS-CoV-2 subgenomic ribonucleic acid (sgRNA), and viral load (VL) by reverse-transcriptase polymerase chain reaction (RT-PCR), and for anti- SARS-CoV-2. Cluster and quadratic discriminant analyses of results were performed. Results Among 229 recruits isolated for COVID-19, those with a RT-PCR cycle threshold >30.49 (sensitivity 95%, specificity 96%) or having sgRNA log10 RNA copies/mL <3.09 (sensitivity and specificity 96%) at entry into isolation were likely SARS-CoV-2 uninfected. Viral load >4.58 log10 RNA copies/mL or anti-SARS-CoV-2 signal-to-cutoff ratio <1.38 (VL: sensitivity and specificity 93%; anti-SARS-CoV-2: sensitivity 83%, specificity 79%) had comparatively lower sensitivity and specificity when used alone for discrimination of infected from uninfected. Conclusions Orthogonal laboratory assays used in combination with RT-PCR may have utility in determining SARS-CoV-2 infection status for decisions regarding isolation.
A novel lncRNA-miRNA-mRNA triple network identifies lncRNA XIST as a biomarker for acute myocardial infarction

Despite the well-established role of long non-coding RNAs (lncRNAs) across various biological processes, their mechanisms in acute myocardial infarction (AMI) are not fully elucidated. The GSE34198 dataset from the Gene Expression Omnibus (GEO) database, which comprised 49 specimens from individuals with AMI and 47 specimens from controls, was extracted and analysed using the weighted gene co-expression network analysis (WGCNA) package. Twenty-seven key genes were identified through a combination of the degree and gene significance (GS) values, and the CDC42 (degree = 64), JAK2 (degree = 41), and CHUK (degree = 30) genes were identified as having the top three-degree values among the 27 genes. Potential interactions between lncRNA, miRNAs and mRNAs were predicted using the starBase V3.0 database, and a lncRNA-miRNA-mRNA triple network containing the lncRNA XIST, twenty-one miRNAs and three hub genes (CDC42, JAK2 and CHUK) was identified. RT–qPCR validation showed that the expression of the JAK2 and CDC42 genes and the lncRNA XIST was noticeably increased in samples from patients with AMI compared to normal samples. Pearson’s correlation analysis also proved that JAK2 and CDC42 expression levels correlated positively with lncRNA XIST expression levels. The area under ROC curve (AUC) of lncRNA XIST was 0.886, and the diagnostic efficacy of the lncRNA XIST was significantly better than that of JAK2 and CDC42. The results suggested that the lncRNA XIST appears to be a risk factor for AMI likely through its ability to regulate JAK2 and CDC42 gene expressions, and it is expected to be a novel and reliable biomarker for the diagnosis of AMI.