Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential response of HBV envelope-specific CD4+ T cells is related to HBsAg loss after stopping nucleos(t)ide analogue therapy

Background and Aim: Long-term maintenance of viral control, even HBsAg loss, remains a challenge for chronic hepatitis B (CHB) patients undergoing nucleos(t)ide analogue (NA) discontinuation. This study aimed to investigate the relationship between HBV-specific T-cell responses targeting peptides spanning the whole proteome and clinical outcomes in CHB patients after NA discontinuation. Approach and Results: Eighty-eight CHB patients undergoing NA discontinuation were classified as responders (remained relapse-free up to 96 weeks) or relapsers (relapsed patients who underwent NA retreatment for up to 48 weeks and reachieved stable viral control). HBV-specific T-cell responses were detected at baseline and longitudinally throughout the follow-up. We found responders had a greater magnitude of HBV polymerase (Pol)-specific T-cell responses than relapsers at baseline. After long-term NA discontinuation, simultaneously enhanced HBV Core-induced and Pol-induced responses were observed in responders. Particularly, responders with HBsAg loss possessed enhanced HBV Envelope (Env)-induced responses after short-term and long-term follow-up. Notably, CD4+T cells accounted for the predominance of HBV-specific T-cell responses. Correspondingly, CD4-deficient mice showed attenuated HBV-specific CD8+T-cell responses, reduced HBsAb-producing B cells, and delayed HBsAg loss; in contrast, in vitro addition of CD4+T cells promoted HBsAb production by B cells. Besides, IL-9, rather than PD-1 blockade, enhanced HBV Pol-specific CD4+T-cell responses. Conclusion: HBV-specific CD4+T-cell responses induced by the targeted peptide possess specificities for long-term viral control and HBsAg loss in CHB patients undergoing NA discontinuation, indicating that CD4+T cells specific to distinct HBV antigens may endow with divergent antiviral potential.
Persistent Firing in Hippocampal CA1 Pyramidal Cells in Young and Aged Rats

Abstract Persistent neuronal firing is often observed in working memory and temporal association tasks both in humans and animals, and is believed to retain necessary information in these tasks. We have reported that hippocampal CA1 pyramidal cells are able to support persistent firing through intrinsic mechanisms in the presence of cholinergic agonists. However, it still remains largely unknown how persistent firing is affected by the development of animals and aging. Using in vitro patch-clamp recordings from CA1 pyramidal cells in rat brain slices, we first show that the cellular excitability of these aged rats was significantly lower than that of the young rats, responding with fewer spikes to current injection. In addition, we found age-dependent modulations of input resistance, membrane capacitance, and spike width. However, persistent firing in aged (approximately two-year-old) rats was as strong as that in young animals, and the properties of persistent firing were very similar among different age groups. In addition, medium spike afterhyperpolarization potential (mAHP), was not increased by aging and did not correlate with the strength of persistent firing. Lastly, we estimated the depolarization current induced by the cholinergic activation. This current was proportional to the increased membrane capacitance of the aged group and was inversely correlated with their intrinsic excitability. These observations indicate that robust persistent firing can be maintained in aged rats despite reduced excitability, because of the increased amount of cholinergically induced positive current.
Impact of Spousal Donation on Postoperative Outcomes of Living-donor Lobar Lung Transplantation

Background. The effect of human leukocyte antigen mismatches between donors and recipients on postoperative outcomes of lung transplantation remains controversial. We retrospectively reviewed adult recipients receiving living-donor lobar lung transplantation (LDLLT) to examine the difference in de novo donor-specific antibody (dnDSA) development and clinically diagnosed unilateral chronic lung allograft dysfunction per graft (unilateral CLAD) between lung grafts donated by spouses (nonblood relatives) and nonspouses (relatives within the third degree). We also investigated the difference in prognoses between recipients undergoing LDLLTs including spouse donors (spousal LDLLTs) and not including spouse donors (nonspousal LDLLTs). Methods. In this study, 63 adult recipients undergoing LDLLTs (61 bilateral and 2 unilateral LDLLTs from 124 living donors) between 2008 and 2020 were enrolled. The cumulative incidence of dnDSAs per lung graft was calculated, and prognoses were compared between recipients undergoing spousal and nonspousal LDLLTs. Results. The cumulative incidence of both dnDSAs and unilateral CLAD in grafts donated by spouses was significantly higher than that in grafts donated by nonspouses (5-y incidence of dnDSAs: 18.7% versus 6.4%, P = 0.038; 5-y incidence of unilateral CLAD: 45.6% versus 19.4%, P = 0.011). However, there were no significant differences in the overall survival or chronic lung allograft dysfunction-free survival between recipients undergoing spousal and nonspousal LDLLTs (P > 0.99 and P = 0.434, respectively). Conclusions. Although there were no significant differences in prognoses between spousal and nonspousal LDLLTs, more attention should be paid to spousal LDLLTs because of the higher development rate of dnDSAs and unilateral CLAD.
Nonlinear aeroelastic characterization of wind turbine blades

A nonlinear aeroelastic characterization of wind turbine blades is performed. A two-dimensional aerodynamic model based on the quasi-steady approximation is coupled with a plunging and pitching blade section. The governing nondimensional equations are derived. The normal form of the Hopf bifurcation is derived and used to characterize the behavior of the system. Using linear analysis, it is demonstrated that, as the blade radius and/or operating rotational speed are increased, wind turbine blades become more susceptible to flutter at freestream velocities that are close to the cut-out speed. The nonlinear analysis, based on the normal form of the Hopf bifurcation, shows that, depending on the nonlinear structural parameters and initial conditions, subcritical instability may take place which means that high limit-cycle oscillation amplitudes may take place at freestream velocities that are lower than the linear flutter speed.
Excretion and residue depletion of cannabinoids in beef cattle fed hempseed cake for 111 days

Abstract Thirty-two crossbred heifers were fed either a control diet or 20% (dry matter basis) hempseed cake in a complete ration for 111 days; of the cattle fed hempseed cake, four each were harvested with 0, 1, 4, and 8-day withdrawal periods. Urine and plasma were collected during the feeding and withdrawal periods and liver, kidney, skeletal muscle, and adipose tissue were collected at harvest. Total cannabinoid (n = 10) concentration of hempseed cake averaged 11.3 ± 11.7 mg kg−1 across the feeding period with total cannabidiol and tetrahydrocannabinol (CBD/THC) concentrations of 1.3 ± 0.8 mg kg−1. Neutral cannabinoids (cannabinol [CBN], CBD/THC, and cannabidivarin [CBDV]) were not detected in plasma or urine, but CBD/THC was measured in adipose tissue at all withdrawal periods (6.3 ± 2.1 to 10.1 ± 2.5 ng g−1). In contrast, cannabinoid acids (cannabinolic acid [CBNA], cannabidiolic acid [CBDA]/tetrahydrocannabinolic acid [THCA], cannabichromenic acid [CBCA], and cannabidivarinic acid [CBDVA]) were sporadically detected (<15 ng mL−1) in plasma and urine of cattle fed hempseed cake. Cannabinoid acids were depleted from liver by withdrawal day 4, but could still be measured (<1 ng g−1) in kidney of some animals harvested on withdrawal day 8. Assessment of human exposures to CBD/THC residues through the consumption of beef fat from animals fed hempseed cake suggests that the probability of consuming the equivalent of an acute reference dose (ARfD) is remote, even with the use of a conservative reference dose ARfD (1 μg kg−1 body weight).
Translation and validation of a Swedish version of the Visual Vertigo Analogue Scale

Abstract Purpose The present study aimed to construct and validate a Swedish translation (VVAS-S) of the Visual Vertigo Analogue Scale (VVAS). Materials and Methods The original English VVAS was translated into Swedish by the two authors and back-translated by an independent professional translator. Pilot-tests were performed on two healthy participants and five patients suffering from Visually Induced Dizziness (VID). The translation was deemed understandable by all subjects. Twenty-one patients with VID were recruited to complete the VVAS-S, once in-lab and once at home after 2–3 weeks. Cronbach’s alpha, inter-item consistency and internal consistency were calculated. Results Test-retest values were reliably strong across all items. Cronbach’s alpha was 0.843, which is considered to represent very-high reliability. The corrected-item total-correlation was above 0.3 for all items, meaning they were appropriately associated with one-another. Fourteen out of 36 inter-item correlation interactions were within the 0.2–0.4 range. Conclusions The VVAS-S was found to be comparable to the original VVAS in terms of internal reliability. The translation was perceived as easy to implement by all participants and can be considered ready for clinical use in a Swedish-speaking setting. Item-specific correlations may be valuable for developing future vertigo questionnaires. Key messages The Swedish version of the Visual Vertigo Analogue Scale is a questionnaire suitable for evaluating visually induced dizziness in a Swedish population. This study found that the Swedish questionnaire was comparable to the original in terms of internal consistency. The Swedish Visual vertigo Analogue Scale can be found as an appendix to this article.
Magnetic resonance imaging in screening women at high risk of breast cancer: A meta-analysis

Background: Magnetic resonance imaging (MRI) is more accurate than mammography in screening for breast cancer. Exposure to ionizing radiation from repeated diagnostic X-rays may be a cause of breast cancer. Methods: We conducted systematic searches on PubMed, Cochrane and Embase to identify studies on women who underwent mammography or MRI screening. A meta-analysis was performed to compare the detection rate of breast cancer by mammography, MRI or both. Results: A total of 18 diagnostic publications were identified and included in the meta-analysis. Among the 1000 screened women, MRI alone increased the detection rate of breast cancer by 8 compared with mammography alone (RR 0.48, 95% CI 0.42–0.54), and MRI plus mammography increased the detection rate of breast cancer by 1 compared with MRI alone (RR 0.86, 95% CI 0.78–0.96). Subgroup analysis demonstrated that the diagnostic efficacy of MRI plus mammography in breast was obviously better than that of MRI alone or mammography alone. Conclusions: Screening with MRI alone might be the best choice for women at high risk of breast cancer.
In Vivo Pharmacokinetic and Pharmacodynamic Properties of the Antiarrhythmic Molecule ent-Verticilide

The unnatural verticilide enantiomer (ent-verticilide) is a selective and potent inhibitor of cardiac ryanodine receptor (RyR2) calcium release channels and exhibits antiarrhythmic activity in a murine model of catecholaminergic polymorphic ventricular tachycardia (CPVT). To determine verticilide’s pharmacokinetic and pharmacodynamic properties in vivo, we developed a bioassay to measure nat- and ent-verticilide in murine plasma and correlated plasma concentrations with antiarrhythmic efficacy in a mouse model of CPVT. nat-Verticilide rapidly degraded in plasma in vitro, showing >95% degradation within 5 minutes, whereas ent-verticilide showed <1% degradation over 6 hours. Plasma was collected from mice following intraperitoneal administration of ent-verticilide at two doses (3 mg/kg, 30 mg/kg). Peak Cmax and area under the plasma-concentration time curve (AUC) scaled proportionally to dose, and the half-life was 6.9 hours for the 3-mg/kg dose and 6.4 hours for the 30-mg/kg dose. Antiarrhythmic efficacy was examined using a catecholamine challenge protocol at time points ranging from 5 to 1440 minutes after intraperitoneal dosing. ent-Verticilide inhibited ventricular arrhythmias as early as 7 minutes after administration in a concentration-dependent manner, with an estimated potency (IC50) of 266 ng/ml (312 nM) and an estimated maximum inhibitory effect of 93.5%. Unlike the US Food and Drug Administration-approved pan-RyR blocker dantrolene, the RyR2-selective blocker ent-verticilide (30 mg/kg) did not reduce skeletal muscle strength in vivo. We conclude that ent-verticilide has favorable pharmacokinetic properties and reduces ventricular arrhythmias with an estimated potency in the nanomolar range, warranting further drug development. SIGNIFICANCE STATEMENT ent-Verticilide has therapeutic potential to treat cardiac arrhythmias, but little is known about its pharmacological profile in vivo. The primary purpose of this study is to determine the systemic exposure and pharmacokinetics of ent-verticilide in mice and estimate its efficacy and potency in vivo. The current work suggests ent-verticilide has favorable pharmacokinetic properties and reduces ventricular arrhythmias with an estimated potency in the nanomolar range, warranting further drug development.
Investigation of the medium-term effect of osteoprotegerin/bone morphogenetic protein 2 combining with collagen sponges on tendon-bone healing in a rabbit

Background Osteoprotegerin (OPG) and bone morphogenetic protein-2 (BMP-2) could be administered sequentially to promote tendon-bone healing. There remain several unresolved issues in our previously published study: a) the release kinetics of OPG/BMP-2 from the OPG/BMP-2/collagen sponge (CS) combination in vitro remained unclear; b) the medium-term effect of the OPG/BMP-2/CS combination was not analyzed. Hence, we design this study to address the issues mentioned above. Methods 30 rabbits undergoing anterior cruciate ligament reconstruction (ACLR) with an Achilles tendon autograft randomly received one of the 3 delivery at the femoral and tibial tunnels: OPG/BMP-2, OPG/BMP-2/CS combination, and nothing (blank control). At 8 and 24 weeks post-surgery, the biomechanical tests and histologic analysis were used to evaluate the tendon-bone healing. Results In mechanical tests, the OPG/BMP-2/CS group showed a higher final failure load and stiffness than the other groups at 8 and 24 weeks. Additionally, the maximum stretching distance showed a decreasing trend. The mechanical failure pattern of samples shifted from a tunnel pull-away to a graft midsubstance rupture after OPG/BMP-2/CS-treated. From histological analysis, the OPG/BMP-2/CS treatment increased the amount of collagen fibers (collagen I and II) and promoted fibrocartilage attachment. Conclusion CS as a carrier promotes the medium-term effect of OPG and BMP-2 on tendon-bone healing at the tendon-bone interface in a rabbit ACLR model. OPG, BMP-2 and CS were already applied in several clinical practice, but a further study of clinic use of OPG/BMP-2/CS is still needed.
Medial Gastrocnemius Muscle Properties of Children With Cerebral Palsy After Different Tone Treatments

Objective Spasticity in children with cerebral palsy can be managed by a spectrum of approaches, from conservative therapy, to temporary botulinum toxin A injections, to permanent transection of sensory nerves with a selective dorsal rhizotomy. This pilot study investigated whether these three tone management approaches are associated with histological and biochemical properties of the medial gastrocnemius. Design A convenience sample of children with cerebral palsy undergoing gastrocnemius lengthening surgery was enrolled. Intraoperative biopsies were obtained from three individuals (one each: minimal tone treatment; frequent gastrocnemius botulinum toxin A injections; previous selective dorsal rhizotomy). All individuals had plantarflexor contractures, weakness, and impaired motor control before the biopsy. Results Differences between participants were observed for muscle fiber cross-sectional area, fiber type, lipid content, satellite cell density, and centrally located nuclei. The most pronounced difference was the abundance of centrally located nuclei in the botulinum toxin A participants (52%) compared with the others (3–5%). Capillary density, collagen area and content, and muscle protein content were similar across participants. Conclusions Several muscle properties seemed to deviate from reported norms, although age- and muscle-specific references are sparse. Prospective studies are necessary to distinguish cause and effect and to refine the risks and benefits of these treatment options.
Incidence rate and risk factors of surgical wound infection in general surgery patients: A cross‐sectional study

Hospital‐acquired infections (HAIs) are considered a major challenge in health care systems. One of the main HAIs, playing an important role in increased morbidity and mortality, is surgical wound infection. Therefore, this study aimed to determine the incidence rate and risk factors of surgical wound infection in general surgery patients. This cross‐sectional study was performed on 506 patients undergoing general surgery at Razi hospital in Rasht from 2019 to 2020. Bacterial isolates, antibiotic susceptibility pattern, antibiotic administration, and its type, operation duration and shift, the urgency of surgery, people involved in changing dressings, length of hospitalisation, and levels of haemoglobin, albumin, and white blood cells after surgery were assessed. The frequency of surgical wound infection and its association with patient characteristics and laboratory results were evaluated. The SPSS software package (version 16.0, SPSS Inc., Chicago, IL, USA) was used to analyse the data. Quantitative and qualitative variables were presented using mean (standard deviation) and number (percentage). The Shapiro–Wilk test was used to evaluate the normality of the data in this study. The data did not have a normal distribution. Hence, χ2 and Fisher's exact tests were used to evaluate the relationship between variables. Surgical wound infection occurred in 4.7% (24 cases) of patients with a mean age of 59.34 (SD = 14.61) years. Preoperative (>3 days) and postoperative (>7 days) hospitalisation, history of immunodeficiency (P < 0.001), and interns responsible for changing dressings (P = 0.021) were associated with surgical wound infection incidence. About 9.5% and 4.4% of surgical wound infection cases were significantly associated with pre‐ and postoperative antibiotic use. Gram‐positive cocci were the most prevalent strains isolated from 24 surgical wound infection cases (15/24, 62.5%). Among these, Staphylococcus aureus was the predominant species, followed by coagulase‐negative staphylococci. In addition, the most common Gram‐negative isolates identified were Escherichia coli bacteria. Overall, administration of antibiotics, emergency surgery, surgery duration, and levels of white blood cells and creatinine were identified as surgical wound infection‐associated risk factors. Identifying important risk factors could help control or prevent surgical wound infections.
Changes in the bacterial community colonizing extracted and non-extracted tannin-rich plants in the rumen of dromedary camels

Leguminous trees and saltbushes provide potential alternatives to conventional feeds to overcome feed deficiency in arid and semi-arid countries. However, these plants are rich in antinutritional factors that have adverse effects on rumen microbiota and the host- animal. Some rumen microbiota detoxifies plants’ secondary metabolites; thus, understanding plant-microbe interaction in the rumen could improve the plants’ utilization. This study investigated the bacterial colonization and degradation of non-extracted and extracted tanniniferous plants: Atriplex halimus, Acacia saligna, and Leucaena leucocephala, in the rumen of three fistulated camels at 6 and 12 hours. The results showed that these plants have high nutritional value and tannins contents. The rumen degradation and microbial diversity of plant-attached bacteria varied according to plant type and phenols’ extraction. Atriplex and leucaena showed higher microbial diversity at 6 and 12h, respectively. Bacteroidetes and Firmicutes were the main bacterial phyla, and the main genera were Prevotella, RC9_gut_group, Butyrivibrio that overrepresented in non-extracted plants (P<0.05). Fibrobacteres and Anaerovibrio showed sensitivity to plant toxins and Ruminococcus attached to plants with lower tannins. Several bacterial genera in the camel rumen have the potential to resist antinutritional factors in fodder plants, which could be used to improve the performance of grazing animals.
Unicompartmental knee arthroplasty versus high tibial osteotomy for medial knee osteoarthritis: A systematic review and meta-analysis

We aimed to systematically compare the clinical and functional outcomes between unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO) for the treatment of medial knee osteoarthritis (KOA). Literatures were searched from PubMed, EMBASE, the Cochrane library, Wanfang DATA, China National Knowledge Infrastructure (CNKI) and SinoMed database until December 2020. Studies comparing postoperative clinical and functional outcomes of UKA versus HTO were included. Totally, 38 studies were included, including 2368 patients with 2393 knees in HTO group and 6536 patients with 6571 knees in UKA group. There was significant difference in postoperative pain, revision rate, complications, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score between HTO and UKA groups (p < 0.05). No significant difference was found in excellent/good surgical results, Lysholm, Hospital for Special Surgery (HSS) score, Knee Society Knee (KSS) score, knee and function score of Knee Society (KSFS) score and Tegner score between these two groups (p > 0.05). UKA produced less postoperative pain, less complications and superior WOMAC score, whereas HTO offered extended range of motion (ROM) and less revision rate.
Flagellum-driven cargoes: Influence of cargo size and the flagellum-cargo attachment geometry

The beating of cilia and flagella, which relies on an efficient conversion of energy from ATP-hydrolysis into mechanical work, offers a promising way to propel synthetic cargoes. Recent experimental realizations of such micro-swimmers, in which micron-sized beads are propelled by isolated and demembranated flagella from the green algae Chlamydomonas reinhardtii (C. reinhardtii), revealed a variety of propulsion modes, depending in particular on the calcium concentration. Here, we investigate theoretically and numerically the propulsion of a bead as a function of the flagellar waveform and the attachment geometries between the bead and the flagellum. To this end, we take advantage of the low Reynolds number of the fluid flows generated by the micro-swimmer, which allows us to neglect fluid inertia. By describing the flagellar waveform as a superposition of a static component and a propagating wave, and using resistive-force theory, we show that the asymmetric sideways attachment of the flagellum to the bead makes a contribution to the rotational velocity of the micro-swimmer that is comparable to the contribution caused by the static component of the flagellar waveform. Remarkably, our analysis reveals the existence of a counter-intuitive propulsion regime in which an increase in the size of the cargo, and hence its drag, leads to an increase in some components of the velocity of the bead. Finally, we discuss the relevance of the uncovered mechanisms for the fabrication of synthetic, bio-actuated medical micro-robots for targeted drug delivery.