Miracle-dz/UniFAR-FTUs huggingface dataset:
New biologic (Ab-IPL-IL-17) for IL-17-mediated diseases: identification of the bioactive sequence (nIL-17) for IL-17A/F function

Objectives Interleukin (IL) 17s cytokines are key drivers of inflammation that are functionally dysregulated in several human immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis (RA), psoriasis and inflammatory bowel disease (IBD). Targeting these cytokines has some therapeutic benefits, but issues associated with low therapeutic efficacy and immunogenicity for subgroups of patients or IMIDs reduce their clinical use. Therefore, there is an urgent need to improve the coverage and efficacy of antibodies targeting IL-17A and/or IL-17F and IL-17A/F heterodimer. Methods and results Here, we initially identified a bioactive 20 amino acid IL-17A/F-derived peptide (nIL-17) that mimics the pro-inflammatory actions of the full-length proteins. Subsequently, we generated a novel anti-IL-17 neutralising monoclonal antibody (Ab-IPL-IL-17) capable of effectively reversing the pro-inflammatory, pro-migratory actions of both nIL-17 and IL-17A/F. Importantly, we demonstrated that Ab-IPL-IL-17 has less off-target effects than the current gold-standard biologic, secukinumab. Finally, we compared the therapeutic efficacy of Ab-IPL-IL-17 with reference anti-IL-17 antibodies in preclinical murine models and samples from patients with RA and IBD. We found that Ab-IPL-IL-17 could effectively reduce clinical signs of arthritis and neutralise elevated IL-17 levels in IBD patient serum. Conclusions Collectively, our preclinical and in vitro clinical evidence indicates high efficacy and therapeutic potency of Ab-IPL-IL-17, supporting the rationale for large-scale clinical evaluation of Ab-IPL-IL-17 in patients with IMIDs.
Enhancing inter-professional education through low-fidelity simulation

Background An interprofessional education initiative was developed and piloted in 2014 at Queen's University Belfast, within the School of Nursing and Midwifery and the School of Medicine. Aims The aim of the collaboration was to introduce concepts of normal labour and birth to fourth-year medical students, led by final-year midwifery students. Methods A variety of birthing resources were available to the midwifery students to promote interactivity with the medical students, including birthing balls and birth manikins. Artistic licence in relation to planning the activities was encouraged. Significant emphasis was placed on the importance of relationship-building with women in labour, and the concept of being ‘with woman’ was core to all elements of teaching. Midwifery students undertook acting roles such as the labouring woman, partner or midwife role and acted out mini scenarios such as contacting for advice about early labour, positions for labour or positions for birth. Medical students were encourage.
Leveraging osteoclast genetic regulatory data to identify genes with a role in osteoarthritis

Abstract There has been a growing interest in the role of the subchondral bone and its resident osteoclasts in the progression of osteoarthritis (OA). A recent genome-wide association study (GWAS) identified 100 independent association signals for OA traits. Most of these signals are led by noncoding variants, suggesting that genetic regulatory effects may drive many of the associations. We have generated a unique human osteoclast-like cell-specific expression quantitative trait locus (eQTL) resource for studying the genetics of bone disease. Considering the potential role of osteoclasts in the pathogenesis of OA, we performed an integrative analysis of this dataset with the recently published OA GWAS results. Summary data-based Mendelian randomization (SMR) and colocalization analyses identified 38 genes with a potential role in OA, including some that have been implicated in Mendelian diseases with joint/skeletal abnormalities, such as BICRA, EIF6, CHST3, and FBN2. Several OA GWAS signals demonstrated colocalization with more than one eQTL peak, including at 19q13.32 (hip OA with BCAM, PRKD2, and BICRA eQTL). We also identified a number of eQTL signals colocalizing with more than one OA trait, including FAM53A, GCAT, HMGN1, MGAT4A, RRP7BP, and TRIOBP. An SMR analysis identified 3 loci with evidence of pleiotropic effects on OA-risk and gene expression: LINC01481, CPNE1, and EIF6. Both CPNE1 and EIF6 are located at 20q11.22, a locus harboring 2 other strong OA candidate genes, GDF5 and UQCC1, suggesting the presence of an OA-risk gene cluster. In summary, we have used our osteoclast-specific eQTL dataset to identify genes potentially involved with the pathogenesis of OA.
Update on the Geographic Distribution of the Intermediate Host Snails of Schistosoma mansoni on St. Lucia: A Step Toward Confirming the Interruption of Transmission of Human Schistosomiasis

ABSTRACT. To provide information to guide considerations of declaring interruption of transmission of human schistosomiasis due to Schistosoma mansoni on St. Lucia, we undertook an island-wide survey in June–July 2022 to determine the presence of Biomphalaria snails, the intermediate hosts of S. mansoni, and their infection status. Snail surveys were carried out at 58 habitats to determine presence of Biomphalaria snails followed by examination of the collected snails for evidence of infection with S. mansoni. Furthermore, water samples were collected at the snail habitats and screened for presence of S. mansoni DNA using an eDNA approach. We found B. glabrata present in one habitat (Cul de Sac) where it was abundant. Specimens provisionally identified as Biomphalaria kuhniana were recovered from 10 habitats. None of the Biomphalaria specimens recovered were positive for S. mansoni. None of the eDNA water samples screened were positive for S. mansoni. Experimental exposures of both field-derived and laboratory-reared St. Lucian B. glabrata and B. kuhniana to Puerto Rican and Kenyan-derived S. mansoni strains revealed B. glabrata to be susceptible to both and B. kuhniana proved refractory from histological and snail shedding results. We conclude, given the current rarity of B. glabrata on the island and lack of evidence for the presence of S. mansoni, that transmission is unlikely to be ongoing. Coupled with negative results from recent human serological surveys, and implementation of improved sanitation and provision of safe water supplies, St. Lucia should be considered a candidate for declaration of interruption of human schistosomiasis transmission.
[Mixed myelodysplastic and myeloproliferative syndromes].

BACKGROUND An injury to the hemopoietic stem cell may lead to the aplasia of hemopoiesis, myelodysplasia and to an unregulated myeloproliferation. There is not a strict demarcation of them, so that mixed syndromes can develop as are hypoplastic syndromes on one side and mixed myelodysplastic and myeloproliferative syndromes (MDS-MPS) on the other side. METHODS AND RESULTS Among our 616 pts with MDS we looked for those cases, who had beside myelodysplasia signs of myeloproliferation with increased number of blood cells. They were examined in detail including bone-marrow histology, bone marrow cultivation, cytogenetics and bcr-abl gen. Signs of MDS-MPS were found in 22 patients at the first contact with the patient (13 patients had thrombocytemia and 9 patients had leukocytosis). Further 7 patients were diagnosed as MDS, proliferative syndrome developed after several months (MDS-MPS in evolution). The level of thrombocytemia was relatively stable, the number of leukocytes was progressive. All subtypes of MDS were found. All subjects had variable degree of anemia. Ring-sideroblasts and myelofibrosis were frequent finding in MDS-MPS. Men prevailed in patients with leukocytosis. Cytogenetic and cultivation findings were similar to MDS cases, deletion of long arm of chromosome 20 was present in 3 patients. Five patients transformed to acute myeloid leukemia. CONCLUSIONS Sings of myelodysplasia and myeloproliferation were found in 4% of our MDS patients, designated as mixed myelodysplastic and myeloproliferative syndrome (MDS-MPS). In this syndrome beside evident signs of myelodysplasia thrombocythemia or leukocytosis with the release of bone marrow precursors are present. In only one case polycythemia was encountered.
Modeling, Control, and Clinical Validation of an Upper-Limb Medical Education Task Trainer for Elbow Spasticity and Rigidity Assessment

The goal of this study was to validate a series elastic actuator (SEA)-based robotic arm that can mimic three abnormal muscle behaviors, namely lead-pipe rigidity, cogwheel rigidity, and spasticity for medical education training purposes. Key characteristics of each muscle behavior were first modeled mathematically based on clinically-observed data across severity levels. A controller that incorporated feedback, feedforward, and disturbance observer schemes was implemented to deliver haptic target muscle resistive torques to the trainee during passive stretch assessments of the robotic arm. A series of benchtop tests across all behaviors and severity levels were conducted to validate the torque estimation accuracy of the custom SEA (RMSE: ~ 0.16 Nm) and the torque tracking performance of the controller (torque error percentage: < 2.8 %). A clinical validation study was performed with seven experienced clinicians to collect feedback on the task trainer’s simulation realism via a Classification Test and a Disclosed Test. In the Classification Test, subjects were able to classify different muscle behaviors with a mean accuracy > 87 % and could further distinguish severity level within each behavior satisfactorily. In the Disclosed Test, subjects generally agreed with the simulation realism and provided suggestions on haptic behaviors for future iterations. Overall, subjects scored 4.9 out of 5 for the potential usefulness of this device as a medical education tool for students to learn spasticity and rigidity assessment.
Tolerable treatment of glioblastoma with redox-cycling ‘mitocans': a comparative study in vivo

ABSTRACT Objectives: The present study describes a pharmacological strategy for the treatment of glioblastoma by redoxcycling ‘mitocans’ such as quinone/ascorbate combination drugs, based on their tumor-selective redox-modulating effects and tolerance to normal cells and tissues. Methods: Experiments were performed on glioblastoma mice (orthotopic model) treated with coenzyme Q0/ascorbate (Q0/A). The drug was injected intracranially in a single dose. The following parameters were analyzed in vivo using MRI orex vivo using conventional assays: tumor growth, survival, cerebral and tumor perfusion, tumor cell density, tissue redox-state, and expression of tumor-associated NADH oxidase (tNOX). Results: Q0/A markedly suppressed tumor growth and significantly increased survival of glioblastoma mice. This was accompanied by increased oxidative stress in the tumor but not in non-cancerous tissues, increased tumor blood flow, and downregulation of tNOX. The redox-modulating and anticancer effects of Q0/A were more pronounced than those of menadione/ascorbate (M/A) obtained in our previous study. No adverse drug-related side-effects were observed in glioblastoma mice treated with Q0/A. Discussion: Q0/A differentiated cancer cells and tissues, particularly glioblastoma, from normal ones by redox targeting, causing a severe oxidative stress in the tumor but not in non-cancerous tissues. Q0/A had a pronounced anticancer activity and could be considered safe for the organism within certain concentration limits. The results suggest that the rate of tumor resorption and metabolism of toxic residues must be controlled and maintained within tolerable limits to achieve longer survival, especially at intracranial drug administration.
The whole day matters after stroke: Study protocol for a randomized controlled trial investigating the effect of a ‘sit less, move more, sleep better’ program early after stroke

Background Movement-related behaviours, including prolonged sedentary behaviour, physical inactivity, and sleep disorders, are associated with worse functional outcomes poststroke. Addressing these co-dependent behaviours early after stroke may help to optimize recovery and improve overall quality of life for individuals with stroke. Objective This study aims to determine the feasibility and effect of a sit less, move more, sleep better program early after stroke on functional mobility and global disability outcomes, while also exploring imaging and behavioral markers that may influence walking recovery. Methods The study is a single-blind (outcome assessor), single-center, parallel-group, randomized controlled trial. We will enroll 50 patients with acute ischemic stroke within 7 days from symptom onset, aged 18 years or older, and with ongoing walking goals. Demographic and stroke characteristics, including stroke risk factors, neuroimaging, and acute stroke treatments, will be determined and documented. All participants will wear an accelerometer for one week at three different time-points (baseline, 6, and 12 weeks) to assess movement-related behaviours. Following randomization, participants in the intervention arm will receive a sit less, move more, sleep better program for up to 1 hour/day, 5 days/week, for 6 weeks to enhance self-efficacy for change. Participants in the control arm will receive usual inpatient and early supported stroke discharge care. The feasibility outcomes will include reach (enrolled/eligible), retention (completed/enrolled), adverse events, and program adherence. Other outcomes at 6 and 12 weeks include the modified Rankin Scale, Timed-Up and Go, movement-related behaviours, walking endurance, gait speed, cognition, stroke severity and quality of life. Discussion Adopting a whole-day approach to poststroke rehabilitation will provide valuable insights into the relationship between optimizing movement-related behaviours early after stroke and their impact on functional outcomes. Through exploring person-specific behavioural and imaging markers, this study may inform precision rehabilitation strategies, and guide clinical decision making for more tailored interventions.
Determinants of gender disparities in psychological distress among youth and adults in South Africa: Evidence from the 2017 national population-based household survey

Background: Psychological distress has become a significant public health concern, and gender differences in psychological distress are well documented in the literature. This study investigated determinants of gender disparities in psychological distress among youth and adults in South Africa. Methods: This study data used obtained from the 2017 National HIV Prevalence, Incidence, Behaviour, and Communication Survey conducted using a multi-stage stratified random cluster sampling design. Multivariate backward stepwise logistic regression models were used to determine the factors associated with psychological distress among males and females. Results: In the male model, the odds of psychological distress were significantly higher among those who reported fair/poor self-rated health [AOR=1.7% (95% CI: 1.2-2.4), p=0.003], and excessive alcohol users [AOR=1.6% (95% CI: 1.1-2.3), p=0.008]. The odds were significantly lower among those with tertiary education level [AOR=0.5% (95% CI: 0.3-0.9), p=0.031], those from rural formal/farm areas [AOR=0.6% (95% 0.4-1.0), p=0.046], and those who were HIV negative [AOR=0.7% (95% CI: 0.4-1.0), p=0.051]. In the female model, the odds of psychological distress were significantly higher among those who reported fair/poor self-rated health [AOR=2.6% (95% CI: 2.0-3.4), p<0.001], and excessive alcohol users [AOR=2.0% (95% CI: 1.3-3.1), p=0.002]. The odds were significantly lower among the employed [AOR=0.7% (95% CI: 0.5-0.9), p=0.002], those from rural informal/tribal areas [AOR=0.6% (95% CI: 0.5-0.8), p=0.001], rural formal/farm areas [AOR=0.6% (95% CI: 0.4-0.9), p=0.015], and those with correct HIV knowledge and myth rejection [AOR=0.6% (95% CI: 0.4-0.7), p<0.001]. Conclusion: The findings highlight the need for tailored gender-specific interventions and targeting identified high-risk groups. The finding also underscores the importance of integrated interventions to address the adverse effects of harmful alcohol use and HIV-positive serostatus on psychological distress.
Reliability and validity of the T-shirt test for the assessment of unsupported sitting in manual wheelchair users with spinal cord injury

This study aimed to evaluate the validity and reliability of the T-shirt test (TST) in assessing sitting stability under three thigh support conditions and with timed outcomes derived in six ways among individuals with a spinal cord injury (SCI). The TST was performed five times under three thigh support conditions (85%, 55% and 25% of total thigh length) in two evaluations spaced between 7−14 days. For each thigh condition, six different outcomes were derived (average or best time from 2, 3, and 5 trial). All outcomes derivation showed excellent reliability on test day (intraclass correlation coefficient; ICC ≥ 0.997) and excellent test-retest reliability (ICC ≥ 0.874) for each thigh support condition. The TST showed high inverse correlations with the Spinal Cord Independence Measure III (SCIM)-mobility score for all outcomes and support conditions (ρ≥−0.706), except for Best-5; moderate inverse correlations with total SCIM-total scores for most outcome derivations and support conditions (ρ≥−0.636); and a moderate inverse correlation with confidence and capacity domains of Wheelchair Skills Test-Questionnaire for most outcome derivation and support conditions (ρ≥−0.504). The TST could discriminate cervical from high and low thoracic levels of injuries under minimal thigh support condition. Overall, all the TST-derived outcomes and support conditions showed adequate validity and test-retest reliability, but Best-5 had inconsistency. Under the minimal thigh support condition, all outcome derivations except Best-3 could discriminate cervical from other injury-level groups. Although all outcome derivations and thigh support conditions provided reliable results, we recommend using the average of 3 trials under the maximal thigh support condition.
Genomic epidemiology and antibiotic susceptibility profiling of uropathogenic Escherichia coli among children in the United States

ABSTRACT Escherichia coli is the most common cause of urinary tract infections (UTIs) in children, and yet the underlying mechanisms of virulence and antibiotic resistance and the overall population structure of the species is poorly understood within this age group. To investigate whether uropathogenic E. coli (UPEC) from children who developed pyelonephritis carried specific genetic markers, we generated whole-genome sequence data for 96 isolates from children with UTIs. This included 57 isolates from children with either radiologically confirmed pyelonephritis or cystitis and 27 isolates belonging to the well-known multidrug-resistant sequence type ST131, selected to investigate their population structure and antibiotic resistance characteristics. We observed a UPEC population structure that is similar to those reported in adults. In comparison with prior investigations, we found that the full pap operon was more common among UPEC from pediatric cases of pyelonephritis. Further, in contrast with recent reports that the P-fimbriae adhesin-encoding papGII allele is substantially more prevalent in invasive UPEC from adults, we found papGII was common to both invasive and non-invasive UPEC from children. Among the set of ST131 isolates from children with UTIs, we found antibiotic resistance was correlated with known genetic markers of resistance, as in adults. Unexpectedly, we observed that fimH30, an allele of the fimbrial gene fimH often used as a proxy to type ST131 isolates into the most drug-resistant subclade C, was carried by some of the subclade A and subclade B isolates, suggesting that the fimH30 allele could confer a selective advantage for UPEC. IMPORTANCE Urinary tract infections (UTIs), which are most often caused by Escherichia coli, are not well studied in children. Here, we examine genetic characteristics that differentiate UTI-causing bacteria in children that either remain localized to the bladder or are involved in more serious kidney infections. We also examine patterns of antibiotic resistance among strains from children that are part of E. coli sequence type 131, a group of bacteria that commonly cause UTIs and are known to have high levels of drug resistance. This work provides new insight into the virulence and antibiotic resistance characteristics of the bacteria that cause UTIs in children. Urinary tract infections (UTIs), which are most often caused by Escherichia coli, are not well studied in children. Here, we examine genetic characteristics that differentiate UTI-causing bacteria in children that either remain localized to the bladder or are involved in more serious kidney infections. We also examine patterns of antibiotic resistance among strains from children that are part of E. coli sequence type 131, a group of bacteria that commonly cause UTIs and are known to have high levels of drug resistance. This work provides new insight into the virulence and antibiotic resistance characteristics of the bacteria that cause UTIs in children.
SA-RPN: A Spacial Aware Region Proposal Network for Acne Detection

Automated detection of skin lesions offers excellent potential for interpretative diagnosis and precise treatment of acne vulgar. However, the blurry boundary and small size of lesions make it challenging to detect acne lesions with traditional object detection methods. To better understand the acne detection task, we construct a new benchmark dataset named AcneSCU, consisting of 276 facial images with 31777 instance-level annotations from clinical dermatology. To the best of our knowledge, AcneSCU is the first acne dataset with high-resolution imageries, precise annotations, and fine-grained lesion categories, which enables the comprehensive study of acne detection. More importantly, we propose a novel method called Spatial Aware Region Proposal Network (SA-RPN) to improve the proposal quality of two-stage detection methods. Specifically, the representation learning for the classification and localization task is disentangled with a double head component to promote the proposals for hard samples. Then, Normalized Wasserstein Distance of each proposal is predicted to improve the correlation between the classification scores and the proposals' intersection-over-unions (IoUs). SA-RPN can serve as a plug-and-play module to enhance standard two-stage detectors. Extensive experiments are conducted on both AcneSCU and the public dataset ACNE04, and the results show that the proposed method can consistently outperform state-of-the-art methods.
Outcomes of transcatheter edge‐to‐edge repair for atrial functional mitral regurgitation: A meta‐analysis of observational studies

Transcatheter edge‐to‐edge repair (TEER) may have potential benefits in the treatment of atrial functional mitral regurgitation (AFMR), but robust evidence is currently lacking. We conducted a systematic review and meta‐analysis to investigate the clinical outcomes of TEER for AFMR, including comparisons to ventricular functional MR (VFMR).