Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovery and Mechanism of SARS-CoV-2 Main Protease Inhibitors

The emergence of a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents an urgent public health crisis. Without available targeted therapies, treatment options remain limited for COVID-19 patients. Using medicinal chemistry and rational drug design strategies, we identify a 2-phenyl-1,2-benzoselenazol-3-one class of compounds targeting the SARS-CoV-2 main protease (Mpro). FRET-based screening against recombinant SARS-CoV-2 Mpro identified six compounds that inhibit proteolysis with nanomolar IC50 values. Preincubation dilution experiments and molecular docking determined that the inhibition of SARS-CoV-2 Mpro can occur by either covalent or noncovalent mechanisms, and lead E04 was determined to inhibit Mpro competitively. Lead E24 inhibited viral replication with a nanomolar EC50 value (844 nM) in SARS-CoV-2-infected Vero E6 cells and was further confirmed to impair SARS-CoV-2 replication in human lung epithelial cells and human-induced pluripotent stem cell-derived 3D lung organoids. Altogether, these studies provide a structural framework and mechanism of Mpro inhibition that should facilitate the design of future COVID-19 treatments.
Outcomes of a regional variant of botulinum toxin type A in the treatment of essential blepharospasm and hemifacial spasms: A retrospective study

Purpose: The aim of this study was to report the outcomes of a regional variant of botulinum toxin type A (BtA) in essential blepharospasm and hemifacial spasm. Methods: The medical records of all patients with facial dystonias, who received at least one dose of BtA between May 2016 and April 2017 were retrospectively evaluated. The pre- and post-injection severity of symptoms, graded using the Jankovic rating system for essential blepharospasm and the Samsung Medical Center grading system for hemifacial spasm, the complications after each sitting, and the mean symptom-free interval were recorded. A correlation analysis was done to identify factors associated with longer symptom-free intervals. A P value < 0.05 was considered statistically significant. Results: The mean age at presentation was 56.62 ± 10.56 years. The mean duration of follow-up was 1.86 ± 2.06 years. The modal disease severity reduced from 5 to 0 in essential blepharospasm and from 2 to 0 in hemifacial spasm a week after injection of botulinum toxin. The mean symptom-free intervals with doses of 20, 22.5, 25, 30, and 50 units were 102.1 ± 44.7, 132.4 ± 35.3, 147.2 ± 61.6, 124.4 ± 55.1, and 142.4 ± 59.7 days, respectively. The commonest complication was lagophthalmos (26.3%; n = 20). Injections for primary dystonias were associated with longer disease-free intervals than those for secondary dystonias (P = 0.02). In nine sittings, the dose was increased for increased severity or presumed resistance, which resulted in a significant increase in the symptom-free interval (P = 0.004) without an increased incidence of complications (P = 0.48). Conclusion: BtA is safe and effective in the treatment of facial dystonias. The drug is more efficacious for primary facial dystonias.
Biomechanical responses to landing strategies of female artistic gymnasts

ABSTRACT Inconsistencies between sexes in the landing criteria provided by the international gymnastics governing body (FIG) may predispose female gymnasts to lower extremity injury. This study aimed to investigate lower extremity biomechanics when performing the male and female landing strategy. Seven collegiate, female gymnasts (age: 20.5 ± 1.2 years, height: 1.64 ± 0.06 m, mass: 60.4 ± 10.2 kg) performed drop landings using the prescribed women’s and men’s landing strategy. Kinematic and kinetic data from 10 trials of each landing strategy were collected. Differences between landing strategy at individual and group level for key injury risk variables of the lower limb were explored. Group differences (p ≤ .05) were reported in the sagittal range of motion (ROM) at the knees and hips, with the men’s landing strategy eliciting a larger ROM decelerating the body upon impact. Large inter and intra-individual variation was apparent with different movement responses shown across individuals and demonstrating degeneracy as gymnasts satisfied the overall landing objective. These results indicate an individually favoured landing strategy to fulfil the informational constraints and hence supporting the use of a single-subject design. The current study emphasises the potential injury risk associated with the different informational constraints placed on females’ landing strategy by the FIG, whilst recognising the individual gymnasts’ task response. Highlights An increase in the range of motion at the knee and hip may support the recommendation of the men’s landing style. Gymnasts appear to utilise individual landing strategies to complete the landing objective, supporting the use of a single-subject design.
An adaptation of meaning-centered psychotherapy integrating “essential care”: A pilot study

Abstract Introduction There is a growing interest in the emotional state of cancer patients. The main objective of this pilot study is to assess the feasibility, acceptability, and preliminary efficacy of Meaning-Centered Psychotherapy and Essential Care (MCP-EC) in patients with advanced cancer compared with usual psychological support. We define “Essential Care” as the promotion of patient care and self-care through the recall of good care experiences and discussion of the concepts: responsibility, self-compassion, kindness, and attitude. Method Pilot, single-center, and prospective study of 30 patients with advanced cancer and emotional distress. Our adaptation consisted in three session Meaning-Centered Psychotherapy-Palliative Care, plus a fourth session named “Essential Care”. The study was carried out in two phases. First, 20 patients were randomized to one of the two arms: individual MCP-EC (experimental, n = 10) or usual psychological supportive (control, n = 10). In a second phase, 10 patients were assigned consecutively to Group MCP-EC (n = 10). All patients were evaluated at baseline (pre-) and post-intervention with questionnaires for sociodemographic data and clinical scales. Results Nineteen patients completed the 4 sessions of MCP-EC, 9 individual format and 10 group format. Usual supportive intervention was delivered to 10 control patients. Total 28 patients completed pre- and post-treatment evaluations. There were no pre- vs. post-differences in the evaluations of the control group. In the experimental group, significant pre- vs. post-differences were found in EQ-5D-3L, HADS, FACIT, DM, HAI, SCS-SF, and TD questionnaires. These results indicated that MCP-EC reduced anxiety and depression symptoms, hopelessness, demoralization, as well as increased spiritual well-being and sense of meaning. Participants were satisfied and found the MCP-EC intervention positively. Conclusions This pilot study suggests that the MCP-EC has feasibility, acceptability, and preliminary efficacy reducing the emotional distress in advanced cancer patients. Larger studies are warranted to clarify the strengths and limitations of this psychotherapy.
Mouse and Human Single Pancreatic β Cell Transcriptomics Reveal Sexual Dimorphism of Transcriptomes and Identify Sex-dependent Type 2 Diabetes Altered Genes

Type 2 diabetes, characterized by malfunction of pancreatic β cells, is affected by multiple cues including sex differences. Nevertheless, mechanisms of sex differences in type 2 diabetes susceptibility and pathogenesis remain unclear. Using single-cell RNA sequencing (scRNA-seq) technology, we showed that sexual dimorphism of transcriptome exists in both mouse and human β cells, and differs significantly in human under diabetic condition. Our analysis further revealed the existence of sex-dependent type 2 diabetes altered genes in both mice and human beings, suggesting divergences in pathological mechanisms of type 2 diabetes between sexes. Our results indicated that sex should be taken into consideration when treating diabetes, which was further validated by the sex-matched and sex-mismatched islet transplantation in mice. Compared to sex-matched transplants, sex-mismatched transplants showed downregulation of genes involved in the longevity regulating pathway in β cells and led to impaired glucose tolerance in diabetic mice. Taken together, our findings could advance current understanding of type 2 diabetes pathogenesis with sexually dimorphic perspectives and provide new insights to the development of precision medicine. Context and Significance Amounting evidence has shown that sex plays a crucial role for glucose homeostasis and onset risk of diabetes. Based on pancreatic β cell transcriptome profiling at single cell resolution, we focused on identifying sexually dimorphic transcriptomes and sex-dependent type 2 diabetes genes in both mouse and human. Given the importance revealed by our study that different pathological mechanisms of type 2 diabetes exist between sexes, sex differences should be taken into consideration for innovative precision medicine when treating diabetes. Highlights Sex-biased gene expression pattern exists in both mouse and human β cells, and differs dramatically under diabetic condition in human. In both human and mouse β cells, abundant sex-dependent type 2 diabetes altered genes are identified. Sex-specific interspecies conservation of type 2 diabetes altered metabolic pathways exists. Sex-matched islet transplantation in diabetic mice yields better control of glucose homeostasis than sex-mismatched transplantation. Graphic Abstract
Impregnation of Cellulose Acetate Films with Carvacrol Using Supercritical Carbon Dioxide

TIJANA N. ADAMOVIĆ, University of Valladolid, Department of Chemical Original scientific paper Engineering and Environmental Technology, Valladolid, Spain UDC: 547.913 STOJA L. MILOVANOVIĆ, University of Belgrade, DOI: 10.5937/tehnika1801017A Faculty of Technology and Metallurgy, Belgrade DARKA D. MARKOVIĆ, University of Belgrade, Innovation Center of the Faculty of Technology and Metallurgy, Belgrade IRENA T. ŽIŽOVIĆ, Wroclaw University of Science and Technology, Faculty of Chemistry, Wroclaw, Poland
Drying of thin porous disks from pore network simulations

ABSTRACT Thin porous media (TPM) are porous layers that are characterized by a small thickness, usually orders of magnitude smaller than the lateral dimensions. We present pore network simulation revealing that drying of TPM is substantially different from drying of thicker porous media because of the impact of the small thickness of only a few pore layers on the liquid phase structure during drying. The small thickness limits the long-distance connectivity within the liquid clusters and thus causes the formation of smaller clusters characterized by shorter residence times. As a result of this stronger and earlier liquid phase fragmentation the drying of TPM is shown to be significantly more sensitive to the distribution of the evaporation flux at the surface. It is also shown that the drying behavior transition from thin to thick porous media is progressive. Moreover, it is discussed how an imposed temperature distribution can be used to control the evolution of the liquid cluster distribution in a TPM and thereby the evolution of the evaporation rate.
Mycoplasma genitalium prevalence and macrolide resistance‐associated mutations and coinfection with Chlamydia trachomatis in Southern Jutland, Denmark

This study aims to investigate prevalence of Mycoplasma genitalium and macrolide resistance‐associated mutations and coinfection with other sexually transmitted bacteria in Southern Jutland, Denmark, where this information is very limited. Urinary samples from patients suspected of sexually transmitted bacterial infections collected at primary healthcare facilities in Southern Jutland are routinely tested for Chlamydia trachomatis and Neisseria gonorrhoeae. 601 of these samples were analysed with SpeeDx MG+23S reagents, which can detect M. genitalium and macrolide resistance‐mediating mutations in the 23S rRNA gene. Moreover, 147 C. trachomatis positive urinary samples from routine test were also analysed with the PCR assay to detect M. genitalium. 72 out of 601 samples were detected positive for C. trachomatis (12%), five samples (0.83%) positive for N. gonorrhoeae and 25 samples positive for M. genitalium (4.2%). 14 of the 25 M. genitalium samples were detected having 23S rRNA gene mutations associated with macrolide resistance (56%). 25 of 147 C. trachomatis positive samples were tested positive for M. genitalium (17%) and two of them were positive for M. genitalium and N. gonorrhoeae (1.4%). The high prevalence of M. genitalium and macrolide resistance‐associated mutation and the coinfection with C. trachomatis in the region suggesting that M. genitalium testing should be included in routine sexually transmitted infection screening.
Feasibility of Systems Support Mapping to guide patient-driven health self-management in colorectal cancer survivors

Abstract Objective To evaluate feasibility of System Support Mapping (MAP), a systems thinking activity that involves creating a diagram of existing self-management activities (e.g. symptom management, health behaviors) to facilitate autonomous engagement in optimal self-management. Design One-arm pilot study of MAP in colorectal cancer survivors (NCT03520283). Main outcome measures Feasibility of recruitment and retention (primary outcome), acceptability, and outcome variability over time. Results We enrolled 24 of 66 cancer survivors approached (36%) and 20 completed follow-up (83%). Key reasons for declining participation included: not interested (n = 18), did not perceive a need (n = 9), and emotional distress/overwhelmed (n = 7). Most participants reported that MAP was acceptable (e.g. 80% liked MAP quite a bit/very much). Exploratory analyses revealed a −4.68 point reduction in fatigue from before to 2 weeks after MAP exceeding a minimally important difference (d = −0.68). There were also improvements in patient autonomy (d = 0.63), self-efficacy (for managing symptoms: d = 0.56, for managing chronic disease: d = 0.44), psychological stress (d = −0.45), anxiety (d = −0.34), sleep disturbance (d = −0.29) and pain (d = −0.32). Qualitative feedback enhanced interpretation of results. Conclusions MAP feasibility in colorectal cancer survivors was mixed, predominantly because many patients did not perceive a need for this approach. MAP was acceptable among participants and showed promise for improving health outcomes.
Anxiety and depression among nurses in COVID and non‐COVID intensive care units

Abstract Background Frontline nurses dealing with the coronavirus disease‐2019 (COVID‐19) pandemic face various mental health challenges ranging from excessive stress and anxiety to severe depression. Aims and Objectives To study the comparative prevalence of anxiety and depression, and their contributing factors, between nurses working in intensive care units (ICU) with COVID‐19 patients (COVID ICU) and nurses working in ICU with patients admitted for other reasons (non‐COVID ICU). Design Quantitative comparative cross‐sectional study. Methods All frontline nurses working in COVID and non‐COVID ICUs at a tertiary care university hospital in Nepal were included. The data were collected using Google Forms. The groups were evaluated and compared in terms of various relevant variables with self‐designed socio‐demographic questionnaire, the validated Nepali version of the Hospital Anxiety and Depression Scale (HADS), and the General Health Questionnaire 12 (GHQ‐12). Results The response rate was 100%. Of the 99 nurses who met the inclusion criteria, three were excluded. Out of the 96 nurses included, psychiatric caseness was present in 82 (85.4%). There was no statistically significant difference in the prevalence of psychiatric caseness, anxiety, and depression between the COVID ICU and non‐COVID ICU nurses (caseness of 90.4% vs 79.5%, P = .134; anxiety of 36.5% vs 27.3%, P = .587; and depression of 21.2% vs 9.1%, P = .214, respectively). Among the factors that could potentially lead to psychiatric caseness, anxiety, and depression, statistically significant differences were observed only in relation to sleep disturbances, confidence in caring for patients with COVID‐19 and intentions to discontinue current job, all being significantly higher in COVID ICU nurses. Conclusion Anxiety and depression are common in nurses working in both the COVID and non‐COVID ICUs, although the difference is not statistically significant. Relevance to clinical practice Early assessment of anxiety and depression in nurses working in all ICUs and their active medical and behavioural interventions are important in protecting this vital work force dealing with the pandemic.
Bilateral paracentral acute middle maculopathy and acute macular neuroretinopathy following COVID-19 vaccination

A 35-year-old male patient presented with blurring and black spots in vision after 1 month of the second dose of Covishield vaccination. His visual acuity was 6/6; both eyes and anterior and posterior segment examinations were normal. The optical coherence tomography (OCT) showed multiple hyperreflective lesions involving the nerve fiber layer with back shadowing. In addition, there were hyperreflective spots in the ganglion cell layer and outer plexiform layer with focal loss of external limiting membrane and an intact inner segment/outer segment junction involving the posterior pole in both eyes. The patient was diagnosed with paracentral acute middle maculopathy (PAMM) and acute macular neuroretinopathy (AMN) and advised observation. PAMM and AMN are unreported manifestations following the COVID-19 vaccination.
Appearance Reveals Music Preferences

Disclosing idiosyncratic preferences can help to broker new social interactions. For instance, strangers exchange music preferences to signal their identities, values, and preferences. Recognizing that people’s physical appearances guide their decisions about social engagement, we examined whether cues to people’s music preferences in their physical appearance and expressive poses help to guide social interaction. We found that perceivers could detect targets’ music preferences from photos of their bodies, heads, faces, eyes, and mouths (but not hair) and that the targets’ apparent traits (e.g., submissiveness, neatness) undergirded these judgments. Perceivers also desired to meet individuals who appeared to match their music preferences versus those who did not. Music preferences therefore seem to manifest in appearance, regulating interest in others and suggesting that one’s identity redundantly emerges across different types of cues. People may thus infer others’ music preferences to identify candidates for social bonding.
Vegetation-Environmental Variable Relationshipsin Ponds of Various Origins alongan Altitudinal Gradient

Aquatic vegetation of the mountains and sub-alpine ponds in the Tatra Mountains and adjacent area (Slovakia) has been studied with the aim to provide information about the composition and species richness of macrophytes in relation to environmental factors. Macrophytes were studied in two pond groups: natural ponds of glacial origin and artificial ponds. Simultaneously, eight environmental variables were measured or estimated at each pond. The studied pond groups differed significantly (Mann-Whitney U-test, P<0.01) in almost all recorded environmental variables except for water temperature and pond area. Almost all environmental characteristics showed higher variability in the artificial ponds. In total, 70 macrophyte taxa were found at the study sites consisting of ca 90% of vascular plants and ca 10% of bryophytes. Artificial ponds were characterised by a multi-element vascular plant species group typical for marshy and aquatic habitats of lower altitudes, while Carex rostrata was the only species typical for natural ponds. Species richness differed significantly between the two pond groups, with artificial ponds hosting considerably more species. Species richness of all studied ponds was negatively correlated with altitude and precipitation; *e-mail: richard.hrivnak@savba.sk DOI: 10.15244/pjoes/68155 1576 Kochjarová J., et al.
Measurement of radioactivity level of sand fraction of Nigerian oil sands for environmental impact assessment

ABSTRACT The radioactivity level of the sand fraction of Nigerian oil sands collected from four different locations, namely Ilubirin, Olowo-Irele, Loda, and Orisunbare, Ondo State, Nigeria, were identified and quantified with the view to assess its likely environmental and health impact of the exploration, exploitation, processing, and transportation of the fossil fuel. Soxhlet extractor was used to extract bitumen from the oil sand samples using toluene as extracting solvent. The sand fraction as left-over collected from the thimble after exhaustive extraction was dried in the oven at 70°C for 8 h to remove trace water and extracting solvent. A survey of radioactivity content and associated radiological risks was carried out on the sand fraction samples by means of a well-calibrated gamma-ray spectrometer containing Na-I (Tl) detector. The mean specific activities of 40K, 232Th, and 238U present in the analyzed sand fraction samples were 3131.17 ± 5.71, 147.90 ± 10.85, and 96.28 ± 2.59 Bq/kg, respectively. The results obtained for the absorbed dose rate (AD), annual effective dose rate (AEDR), internal hazard index (Hin), external hazard index (Hex), annual gonadal equivalent dose (AGED), and the representative levels index (Iγr) were 264.380 nGy/h, 0.324 mSv/year, 1.461 Bq/kg, 1.481 Bq/kg, 1903.073 µSvy–1, and 2.185, respectively. The AD values were higher than the population weighted average (60 nGy/h) recommended by UNSCEAR. The Hex and Hin values were above unity for the studied samples except from Ilubirin. The results follow similar trend for all the radiological parameters. The AGED values were higher than the world average (300 µSvy–1) set by UNSCEAR. The average lifetime cancer of mortality risk due to 40K, 232Th, and 238U was 2.09 × 10–3, 4.18 × 10–8, and 1.84 × 10–6, respectively, while that morbidity risks due to 40K, 232Th, and 238U were 3.07 × 10–3, 6.21 × 10–8, and 2.70 × 10–6, respectively. Radiological assessment however indicated that long-term exposure may pose an intrinsic health hazard.
Sexual selection can partly explain low frequencies of Segregation Distorter alleles

The Segregation Distorter (SD) allele found in Drosophila melanogaster distorts Mendelian inheritance in heterozygous males by causing developmental failure of non-SD spermatids, such that greater than 90% of the surviving sperm carry SD. This within-individual advantage should cause SD to fix, and yet SD is typically rare in wild populations. Here, we explore whether this paradox can be resolved by sexual selection, by testing if males carrying three different variants of SD suffer reduced pre- or post-copulatory reproductive success. We find that males carrying the SD allele are just as successful at securing matings as control males, but that one SD variant (SD-5) reduces sperm competitive ability and increases the likelihood of female remating. We then used these results to inform a theoretical model; we found that sexual selection could limit SD to natural frequencies when sperm competitive ability and female remating rate equalled the values observed for SD-5. However, sexual selection was unable to explain natural frequencies of the SD allele when the model was parameterized with the values found for two other SD variants, indicating that sexual selection alone is unlikely to explain the rarity of SD.