Miracle-dz/UniFAR-FTUs huggingface dataset:
Barriers and facilitators to vaccination uptake against COVID-19, influenza, and pneumococcal pneumonia in immunosuppressed adults with immune-mediated inflammatory diseases: A qualitative interview study during the COVID-19 pandemic

Objectives To explore barriers and facilitators to COVID-19, influenza, and pneumococcal vaccine uptake in immunosuppressed adults with immune-mediated inflammatory diseases (IMIDs). Methods Recruiting through national patient charities and a local hospital, participants were invited to take part in an in-depth, one-to-one, semi-structured interview with a trained qualitative researcher between November 2021 and January 2022. Data were analysed thematically in NVivo, cross-validated by a second coder and mapped to the SAGE vaccine hesitancy matrix. Results Twenty participants (75% female, 20% non-white) were recruited. Barriers and facilitators spanned contextual, individual/group and vaccine/vaccination-specific factors. Key facilitators to all vaccines were higher perceived infection risk and belief that vaccination is beneficial. Key barriers to all vaccines were belief that vaccination could trigger IMID flare, and active IMID. Key facilitators specific to COVID-19 vaccines included media focus, high incidence, mass-vaccination programme with visible impact, social responsibility, and healthcare professionals’ (HCP) confirmation of the new vaccines’ suitability for their IMID. Novel vaccine technology was a concern, not a barrier. Key facilitators of influenza/pneumococcal vaccines were awareness of eligibility, direct invitation, and, clear recommendation from trusted HCP. Key barriers of influenza/pneumococcal vaccines were unaware of eligibility, no direct invitation or recommendation from HCP, low perceived infection risk, and no perceived benefit from vaccination. Conclusions Numerous barriers and facilitators to vaccination, varying by vaccine-type, exist for immunosuppressed-IMID patients. Addressing vaccine benefits and safety for IMID-patients in clinical practice, direct invitation, and public-health messaging highlighting immunosuppression as key vaccination-eligibility criteria may optimise uptake, although further research should assess this.
Comments on the absolute flux density scale at low radio frequencies

La connaissance actuelle en matiere d'echelle de la densite de flux absolue aux radiofrequences basses est passee en revue. Il apparait que les 2 echelles couramment acceptees sont mutuellement contradictoires, mais des observations recentes a 38 MHz suggerent une resolution de ce probleme. Ces contradictions peuvent etre surmontees si la decroissance seculaire du flux de Cas A est supposee independante de la frequence. Les consequences en sont discutees.
Large and significantly anisotropic critical current density induced by planar defects in 
CaKFe4As4
 single crystals

Three independent components of critical current density, one for the H//c axis and the other two for the H//ab plane, have been studied in CaKFe4As4 single crystals. When the magnetic field is applied along the c axis, we observed fish-tail-like peaks in the M-H hysteresis loop, and the magnetization at higher temperatures exceeds that at lower temperatures at high fields. When the field is applied parallel to the ab plane, a dip structure is observed in the M-H hysteresis loop near the self-field. In addition, for the H//ab plane, we succeeded in separately evaluating the large and significantly anisotropic in-plane and out-of-plane Jc. Transmission electron microscopy revealed the presence of planar defects parallel to the ab plane in CaKFe4As4, which have not been observed in any other iron-based superconductors. We discuss the possible relationship between the anomalous Jc behavior and the planar defects.
Switching properties of SrBi2Ta2O9 thin films produced by metalorganic decomposition

The process of polarization reversal in a SrBi2Ta2O9 (SBT) thin film capacitor produced by a metalorganic decomposition method was investigated. The switching time (100–600 ns) and the reversible polarization have been measured at different voltages in the range of 0–5 V. It was found that by annealing the SBT sample in AR atmosphere at 400 °C, the switching times were significantly reduced. This indicates that oxygen vacancies in the film speed up nucleation and growth of new domains.
USP17 is required for peripheral trafficking of lysosomes

Expression of the deubiquitinase USP17 is induced by multiple stimuli, including cytokines (IL‐4/6), chemokines (IL‐8, SDF1), and growth factors (EGF), and several studies indicate it is required for cell proliferation and migration. However, the mechanisms via which USP17 impacts upon these cellular functions are unclear. Here, we demonstrate that USP17 depletion prevents peripheral lysosome positioning, as well as trafficking of lysosomes to the cell periphery in response to EGF stimulation. Overexpression of USP17 also increases secretion of the lysosomal protease cathepsin D. In addition, USP17 depletion impairs plasma membrane repair in cells treated with the pore‐forming toxin streptolysin O, further indicating that USP17 is required for lysosome trafficking to the plasma membrane. Finally, we demonstrate that USP17 can deubiquitinate p62, and we propose that USP17 can facilitate peripheral lysosome trafficking by opposing the E3 ligase RNF26 to untether lysosomes from the ER and facilitate lysosome peripheral trafficking, lysosome protease secretion, and plasma membrane repair.
Extracellular vesicles derived from PPRV-infected cells enhance signaling lymphocyte activation molecular (SLAM) receptor expression and facilitate virus infection

Peste des petits ruminants virus (PPRV) is an important pathogen that seriously influences the productivity of small ruminants worldwide. PPRV is lymphotropic in nature and SLAM was identified as the primary receptor for PPRV and other Morbilliviruses. Many viruses have been demonstrated to engage extracellular vesicles (EVs) to facilitate their replication and pathogenesis. Here, we provide evidence that PPRV infection significantly induced the secretion levels of EVs from goat PBMC, and that PPRV-H protein carried in EVs can enhance SLAM receptor expression in the recipient cells via suppressing miR-218, a negative miRNA directly targeting SLAM gene. Importantly, EVs-mediated increased SLAM expression enhances PPRV infectivity as well as the expression of various cytokines related to SLAM signaling pathway in the recipient cells. Moreover, our data reveal that PPRV associate EVs rapidly entry into the recipient cells mainly through macropinocytosis pathway and cooperated with caveolin- and clathrin-mediated endocytosis. Taken together, our findings identify a new strategy by PPRV to enhance virus infection and escape innate immunity by engaging EVs pathway.
Zinc oxide nanoparticles impact the expression of the genes involved in toxin–antitoxin systems in multidrug‐resistant Acinetobacter baumannii

The aim of this study was to investigate the effect of zinc oxide nanoparticles (ZnO‐NPs) on the expression of genes involved in toxin–antitoxin (TA) systems in multidrug‐resistant (MDR) Acinetobacter baumannii. Seventy clinical isolates of A. baumannii were collected from variuos clinical samples. Antimicrobial susceptibility test was determined by disk diffusion. Type II TA system‐related genes including GNAT, XRE‐like, hipA, hipB, hicA, hicB were screened using polymerase chain reaction (PCR). ZnO‐NPs prepared and characterized by field emission scanning electron microscopy and X‐ray diffraction. MIC of ZnO‐NPs of A. baumannii isolates was performed using the microdilution method. The expression of type II TA systems‐related genes were assessed with and without exposure to ZnO‐NPs using real‐time PCR. The highest rate of resistance and sensitivity was observed against cefepime (77.14%), and ampicillin/sulbactam (42.85%), respectively. All A. baumannii isolates were considered as MDR. In this study, three TA loci were identified for A. baumannii including GNAT/XRE‐like, HicA/HicB, and HipA/HipB and their prevalence was 100%, 42%, and 27.1%, respectively. There was no significant relationship between the prevalence of these systems and the origin of A. baumannii. Our data showed significant correlations between the presence of HicA/HicB system and resistance to ceftazidime, meropenem, imipenem, and cefepime (p < 0.05), and the presence of HipA/HipB system and resistance to ceftazidime, meropenem, imipenem, and cefepime (p < 0.05). In presence of ZnO‐NPs, the expression of all studied genes decreased. GNAT and hicB showed the highest and lowest expression changes by 2.4 folds (p < 0.001) and 1.3 folds (p < 0.05), respectively. This study demonstrates the promising potential of nanoparticles to impact the expression of the genes involved in TA Systems. So, the application of ZnO‐NPs may be helpful to design target‐based strategies towards MDRs pathogens for empowered clinical applications by microbiologists and nanotechnologists.
Marked oestrous cycle‐dependent regulation of rat arterial KV7.4 channels driven by GPER1

Kcnq‐encoded KV7 channels (termed KV7.1–5) regulate vascular smooth muscle cell (VSMC) contractility at rest and as targets of receptor‐mediated responses. However, the current data are mostly derived from males. Considering the known effects of sex, the oestrous cycle and sex hormones on vascular reactivity, here we have characterised the molecular and functional properties of KV7 channels from renal and mesenteric arteries from female Wistar rats separated into di‐oestrus and met‐oestrus (F‐D/M) and pro‐oestrus and oestrus (F‐P/E).
Randomized controlled trial to compare the effectiveness and safety of low dose dexamethasone oral mini‐pulse versus diphenylcyclopropenone contact sensitisation in severe pediatric alopecia areata

Oral mini pulse (OMP) corticosteroids and diphencyclopropenone (DPCP) contact sensitisation are commonly used treatment modalities in severe cases of Alopecia areata (AA) in children but with scarce studies comparing the two modalities in children. In this study we aimed to compare the effectiveness and safety of dexamethasone OMP with DPCP contact sensitization in severe non progressive AA in children. This randomized open label study was undertaken in 30 children less than 18 years of age with extensive non progressive AA divided in two groups. Group I included 15 patients who received dexamethasone (5 mg/week) OMP as five tablets of 0.5 mg dexamethasone (i.e., 2.5 mg dexamethasone) on two consecutive days in a week. Group II included 15 patients who were treated with DPCP contact sensitization. The treatment was continued in all patients for 24 weeks. Patients were followed up every 4 weeks and records were maintained. Response rate was 100% in OMP group and 53.3% in DPCP group at 24 weeks. In Group I, complete regrowth was seen in 20% patients, and cosmetically acceptable regrowth in 66.7% while in Group II, complete regrowth was not seen in any of the patients, and cosmetically acceptable regrowth in 20% (p = 0.001). Hair regrowth started at mean duration of 7.7 weeks in Group I, while 11.3 weeks in Group II. Response rate of treatment with dexamethasone OMP leads to a significantly faster and better hair regrowth compared to DPCP contact immunotherapy in non‐progressive extensive AA in children.
A method to identify, dissect and stain equine neuromuscular junctions for morphological analysis

Morphological study of the neuromuscular junction (NMJ), a specialised peripheral synapse formed between a lower motor neuron and skeletal muscle fibre, has significantly contributed to the understanding of synaptic biology and neuromuscular disease pathogenesis. Rodent NMJs are readily accessible, and research into conditions such as amyotrophic lateral sclerosis (ALS), Charcot–Marie–Tooth disease (CMT), and spinal muscular atrophy (SMA) has relied heavily on experimental work in these small mammals. However, given that nerve length dependency is an important feature of many peripheral neuropathies, these rodent models have clear shortcomings; large animal models might be preferable, but their size presents novel anatomical challenges. Overcoming these constraints to study the NMJ morphology of large mammalian distal limb muscles is of prime importance to increase cross‐species translational neuromuscular research potential, particularly in the study of long motor units. In the past, NMJ phenotype analysis of large muscle bodies within the equine distal pelvic limb, such as the tibialis cranialis, or within muscles of high fibrous content, such as the soleus, has posed a distinct experimental hurdle. We optimised a technique for NMJ location and dissection from equine pelvic limb muscles. Using a quantification method validated in smaller species, we demonstrate their morphology and show that equine NMJs can be reliably dissected, stained and analysed. We reveal that the NMJs within the equine soleus have distinctly different morphologies when compared to the extensor digitorum longus and tibialis cranialis muscles. Overall, we demonstrate that equine distal pelvic limb muscles can be regionally dissected, with samples whole‐mounted and their innervation patterns visualised. These methods will allow the localisation and analysis of neuromuscular junctions within the muscle bodies of large mammals to identify neuroanatomical and neuropathological features.
Strength and Balance in Recreational Golfers and Non-Golfers Aged 65-79 Years in Community Settings.

Inactive older adults tend to have decreased strength and balance compared with their more active peers. Playing golf has the potential to improve strength and balance in older adults. The aim of the study was to compare the strength and balance of recreational golfers with non-golfers, aged 65-79 years. Grip strength, single leg balance, and Y Balance Test (YBT) were assessed. Golfers (n = 57) had significantly (right, p = .042; left, p = .047) higher maximal grip strength, than non-golfers (n = 17). Single leg stance times were significantly longer in golfers (right, p = .021; left, p = .001). Normalized YBT reach distances were significantly greater for golfers than non-golfers for composite, posteromedial, and posterolateral directions on both right and left legs. Playing golf appears to be associated with better grip and both static and dynamic balance in 65-79 year olds, indicating that a study of the effects of playing golf is warranted through a larger, fully powered, longitudinal study.
Utility of constraints reflecting system stability on analyses for biological models

Simulating complex biological models consisting of multiple ordinary differential equations can aid in the prediction of the pharmacological/biological responses; however, they are often hampered by the availability of reliable kinetic parameters. In the present study, we aimed to discover the properties of behaviors without determining an optimal combination of kinetic parameter values (parameter set). The key idea was to collect as many parameter sets as possible. Given that many systems are biologically stable and resilient (BSR), we focused on the dynamics around the steady state and formulated objective functions for BSR by partial linear approximation of the focused region. Using the objective functions and modified global cluster Newton method, we developed an algorithm for a thorough exploration of the allowable parameter space for biological systems (TEAPS). We first applied TEAPS to the NF-κB signaling model. This system shows a damped oscillation after stimulation and seems to fit the BSR constraint. By applying TEAPS, we found several directions in parameter space which stringently determines the BSR property. In such directions, the experimentally fitted parameter values were included in the range of the obtained parameter sets. The arachidonic acid metabolic pathway model was used as a model related to pharmacological responses. The pharmacological effects of nonsteroidal anti-inflammatory drugs were simulated using the parameter sets obtained by TEAPS. The structural properties of the system were partly extracted by analyzing the distribution of the obtained parameter sets. In addition, the simulations showed inter-drug differences in prostacyclin to thromboxane A2 ratio such that aspirin treatment tends to increase the ratio, while rofecoxib treatment tends to decrease it. These trends are comparable to the clinical observations. These results on real biological models suggest that the parameter sets satisfying the BSR condition can help in finding biologically plausible parameter sets and understanding the properties of biological systems.
Tumour necrosis factor blockade after asphyxia in foetal sheep ameliorates cystic white matter injury

Abstract Cystic white matter injury is highly associated with severe neurodevelopmental disability and cerebral palsy in preterm infants, yet its pathogenesis remains poorly understood and there is no established treatment. In the present study, we tested the hypothesis that slowly evolving cystic white matter injury after hypoxia-ischaemia is mediated by programmed necrosis initiated by tumour necrosis factor. Tumour necrosis factor blockade was begun 3 days after hypoxia-ischaemia to target the tertiary phase of injury, when most secondary cell death is thought to be complete. Chronically instrumented preterm foetal sheep (0.7 gestation) received 25 min of hypoxia-ischaemia induced by complete umbilical cord occlusion or sham-umbilical cord occlusion (controls, n = 10), followed by intracerebroventricular infusion of the soluble TNF inhibitor, Etanercept, at 3, 8 and 13 days after umbilical cord occlusion (n = 9) or vehicle (n = 9). Foetal brains were processed for histology at 21 days after umbilical cord occlusion. Umbilical cord occlusion with vehicle was associated with a spectrum of macroscopic white matter degeneration, including white matter atrophy, ventriculomegaly and overt temporal lobe cystic white matter injury. Oligodendrocyte maturational arrest and impaired labelling of myelin proteins, characteristic of diffuse white matter injury, was observed in the parietal lobe and surrounding the cystic lesions in the temporal lobe. Etanercept markedly attenuated cystic white matter injury on the side of the intracerebroventricular infusion, with partial contralateral protection. Further, Etanercept improved oligodendrocyte maturation and labelling of myelin proteins in the temporal and parietal lobes. The present study shows that cystic white matter injury reflects late-onset tertiary cell death mediated by delayed neuroinflammation through the tumour necrosis factor pathway. Delayed tumour necrosis factor blockade markedly attenuated cystic white matter injury and restored oligodendrocyte maturation and deficits in myelin protein expression. These data suggest that delayed tumour necrosis factor blockade may represent a viable therapeutic strategy to reduce the risk of cystic and diffuse white matter injury and potentially cerebral palsy after preterm birth, with a surprisingly wide therapeutic window.
The core PCP protein Prickle2 regulates axon number and AIS maturation by binding to AnkG and modulating microtubule bundling

Core planar cell polarity (PCP) genes, which are involved in various neurodevelopmental disorders such as neural tube closure, epilepsy, and autism spectrum disorder, have poorly defined molecular signatures in neurons, mostly synapse-centric. Here, we show that the core PCP protein Prickle-like protein 2 (Prickle2) controls neuronal polarity and is a previously unidentified member of the axonal initial segment (AIS) proteome. We found that Prickle2 is present and colocalizes with AnkG480, the AIS master organizer, in the earliest stages of axonal specification and AIS formation. Furthermore, by binding to and regulating AnkG480, Prickle2 modulates its ability to bundle microtubules, a crucial mechanism for establishing neuronal polarity and AIS formation. Prickle2 depletion alters cytoskeleton organization, and Prickle2 levels determine both axon number and AIS maturation. Last, early Prickle2 depletion produces impaired action potential firing.
The Pioneer Advantage: Filling the blank spots on the map of genome diversity in Europe

Abstract Documenting genome diversity is important for the local biomedical communities and instrumental in developing precision and personalized medicine. Currently, tens of thousands of whole-genome sequences from Europe are publicly available, but most of these represent populations of developed countries of Europe. The uneven distribution of the available data is further impaired by the lack of data sharing. Recent whole-genome studies in Eastern Europe, one in Ukraine and one in Russia, demonstrated that local genome diversity and population structure from Eastern Europe historically had not been fully represented. An unexpected wealth of genomic variation uncovered in these studies was not so much a consequence of high variation within their population, but rather due to the “pioneer advantage. ” We discovered more variants because we were the first to prospect in the Eastern European genome pool. This simple comparison underscores the importance of removing the remaining geographic genome deserts from the rest of the world map of the human genome diversity.
Five decades of sarcoma care at Memorial Sloan Kettering Cancer Center

Early studies of the management of soft tissue sarcoma at Memorial Sloan Kettering Cancer Center were influenced by development of robust prospective long‐term databases. Increasing capacity for molecular diagnostics has identified a myriad of subtypes with definable natural history. Accurate identification of tissue‐specific risk of recurrence and disease‐specific survival have increasingly allowed selective use of surgery, radiation therapy, and target‐specific cytotoxic and immune therapies.
Safety and Dosing Study of a Cholecystokinin Receptor Antagonist in Non‐alcoholic Steatohepatitis

High saturated fat diets have been shown to raise blood levels of cholecystokinin (CCK) and induce nonalcoholic steatohepatitis (NASH). CCK receptors are expressed on stellate cells and are responsible for hepatic fibrosis when activated. The purpose of this study was to test the safety and dose of a CCK receptor antagonist, proglumide, in human participants with NASH. An open‐label single ascending dose study was conducted in 18 participants with clinical NASH based upon steatosis by liver ultrasound, elevated hepatic transaminases, and a component of the metabolic syndrome. Three separate cohorts (N = 6 each) were treated with oral proglumide for 12 weeks in a sequential ascending fashion with 800 (Cohort 1), 1,200 (Cohort 2), and 1,600 (Cohort 3) mg/day, respectively. Blood hematology, chemistries, proglumide levels, a biomarker panel for fibrosis, and symptom surveys were determined at baseline and every 4 weeks. Abdominal ultrasounds and transient elastography utilizing FibroScan were obtained at baseline and at Week 12. Proglumide was well tolerated at all doses without any serious adverse events. There was no change in body weight from baseline to Week 12. For Cohorts 1, 2, and 3, the median percent change in alanine aminotransferase was 8.42, −5.05, and −22.23 and median percent change in fibrosis score by FibroScan was 8.13, −5.44, and −28.87 (kPa), respectively. Hepatic steatosis as measured by controlled attenuation parameter score significantly decreased with proglumide, (P < 0.05). Blood microRNA biomarkers and serum 4‐hydroxyproline were consistent with decreased fibrosis at Week 12 compared with baseline. These findings suggest proglumide exhibits anti‐inflammatory and anti‐fibrotic properties and this compound is well tolerated in participants with NASH.