Background: The importance of intra-articular corticosteroid treatment for osteoarthritis with its possible adverse effects requires a comprehensive review. Objectives: This review answers the following questions: 1) What evidence is available regarding the symptom-modifying and disease-modifying changes related to a single intra-articular corticosteroid injection for treating osteoarthritis? Moreover, 2) What evidence suggests corticosteroids are detrimental to equine joint health? Study design: Systematic review. Methods: A systematic search was conducted in June/2022 in PubMed, CAB, and the Web of Science. Inclusion criteria were applied to titles and abstracts. For each question, further criteria were applied. The risk of bias was assessed according to the study design. Results: We generated 6,417 titles, and 23 articles fit all inclusion criteria for single-injection corticosteroid treatments; 21 were included regarding corticosteroid effects on joint health. Studies were usually rated as having an unclear risk of bias. Single-injection protocols lead to short-term symptom-modifying osteoarthritic changes with conflicting results regarding disease-modifying osteoarthritis. Healthy joints demonstrated disturbances in metabolism and tissue changes, with dose-dependent effects found in vitro. Main limitations: There is a lack of studies regarding the topics–primarily for equine species. Conclusions: Symptom-modifying osteoarthritic changes after a single injection are short-term; however, a consistent disease-modifying osteoarthritis effect is yet to be established. Joint health appears to be disturbed by corticosteroids as their effects on normal joints show adverse changes in tissues and metabolism.

Objective To identify primary care recorded factors associated with the short-term human papillomavirus (HPV) vaccination among girls and female adolescents. Methods We used the Spanish Pharmacoepidemiological Research Database for Public Health System to identify girls aged 9-18 years in 2007-2016 with ≥1 year of primary care data (start date) and collect baseline characteristics and consultations. The link between those factors and the 1-year HPV vaccination was assessed through multivariate adjusted Odds Ratios (OR; 95% CI). Results Among 388,669 girls identified, 14,999 were vaccinated against HPV during the first year. The vaccination decreased among girls consulting for social (0.62; 0.55-0.70) or adaptation (0.60; 0.38-0.93) problems, prescriptions of benzodiazepines (0.58; 0.35-0.94) or drugs for gastrointestinal symptoms (0.58; 0.38-0.89), with recorded tuberculosis test (0.68; 0.52-0.87), B and C meningitis (0.46; 0.43-0.50) vaccination, consulting the doctor in the last 3 months (0.92; 0.87-0.98) and with severe thinness (0.68; 0.59-0.78) or obesity (0.88; 0.78-0.99). The odds increased among girls with abdominal pain (1.10; 1.04-1.16), prescriptions in the last 3 months (1.17; 1.10-1.25), and vaccinations against chickenpox (1.16; 1.07-1.27), influenza (1.23; 1.08-1.40), hepatitis (1.46; 1.35-1.58) and diphtheria-tetanus (1.91; 1.82-2.01). Conclusions The correlation between the HPV and other vaccinations suggested medical (contra)indications or willingness and knowledge/beliefs that might affect different vaccinations similarly. The higher frequency of the HPV vaccination among females requiring specific treatments or with abdominal pain suggested vulnerability to HPV complications. While a decreased HPV vaccination linked to certain social and personal situations (and benzodiazepines treatment) requires further research.

Objective: We sought to characterize point-of-care lung ultrasound (LUS) findings in children with asthma exacerbations and to determine whether the presence and magnitude of findings were associated with asthma severity. Methods: We enrolled a convenience sample of patients aged 5-18 years presenting with acute asthma exacerbation to a tertiary care pediatric emergency department. Severity of an asthma exacerbation (mild, moderate, severe) was assessed within 1-hour of the LUS using the Hospital Asthma Severity Score, a validated asthma assessment tool. LUS was performed by trained pediatric emergency providers . The presence of LUS findings (any B-lines, ≥3 B-lines per view, consolidations, pleural effusion and pleural line abnormalities) was assessed using a standardized criterion. Results: A total of 111 patients with a median age of 8 years (IQR 6, 12) were enrolled. LUS was positive in 57% of patients. Pleural line abnormalities were observed in 34%, B-lines in 29%, consolidations <1cm in 24%, and consolidations ≥1cm in 7 %. Patients with moderate and severe asthma exacerbations were more likely to have any B-lines (31% and 43%, respectively) than patients with mild exacerbations (12%; p= 0.021), however the presence of ≥3 B-lines did not differ across severity groups. The presence of other findings did not differ based upon asthma severity. Conclusions: LUS findings are commonly observed in patients presenting with asthma exacerbations. While B-lines were more likely to be found in exacerbations of higher severity, LUS findings associated with pediatric pneumonia did not correlate with severity. These findings provide valuable information for the diagnostic use of LUS.

Background: To evaluate the predictive value of a nomogram with Ki-67 in overall and disease-free survival in glioma patients. Methods: A total of 76 patients diagnosed with glioma were enrolled. The baseline data and followups were retrospectively collected from medical records. The associations between Ki-67 and survival status were examined using log-rank test, univariate and multivariate Cox proportional hazard regression models. Calibrations were performed to validate the established nomograms. Results: Ki-67 negative group showed a longer OS survival time and a longer PFS survival time with log-rank test (x2=16.101, P<0.001 and x2=16.961, P<0.001). Age older than 50 years (HR=2.074, 95% CI: 1.097-3.923), abnormal treatment (HR=2.932, 95% CI: 1.343-6.403) and Ki-67 positive (HR=2.722, 95% CI: 1.097-6.755) were the independent predictive factors of death. High grade pathology (HR=2.453, 95% CI: 1.010-5.956) and Ki-67 positive (HR=2.200, 95% CI: 1.043-4.639) were the independent predictive factors of recurrence. The C-index for the nomogram of OS and PFS were 0.745 and 0.723, respectively. The calibration results showed that the nomogram could predict the overall and disease-free 1-year survival of glioma patients. Conclusion: The nomograms with Ki-67 as independent risk factor for OS and PFS could provide clinical consultation in the treatment and follow-up of malignant glioma.

The use of automation in mining can be found at all stages of the mining process, covering exploration, excavation, loading, transportation, mineral processing, and search and rescue missions in emergency situations. Due to the harsh conditions during an underground mine disaster, robots can be of great assistance to rescue teams by entering areas that are unsafe for human rescuers, locating trapped workers and collecting valuable data. The design and implementation of mine rescue robots is characterized by great complexity since it encompasses the consideration of a great range of components and requirements. However, comprehensive guidelines for design and deployment of robots in harsh underground environments have not been established. As a result, the developers of mine rescue robots (MRRs) are to exercise their own judgment on the development and evaluation of the platform functionalities. This review attempts an extensive discussion of design and functionality requirements based on the common practices and lessons learned from the existing MRRs. Common considerations, as well as current and future trends are identified with the aim of facilitating future research and development on mine search and rescue robots.

Marchiafava-Bignami disease: prompt diagnosis made by magnetic resonance brain imagingSatroi Akita, M.D, 1,2Takeshi Takakuwa, M.D. 1Kouji Kajinami, M.D. 21. Department of Internal Medicine, Nanto Chuo Hospital, Nanto City, Toyama, Japan2. Department of Cardiology, Kanazawa Medical University, Uchinada, Ishikawa, JapanCorrespondence should be addressed to:Kouji Kajinami, M.D.Department of Cardiology, Kanazawa Medical University, 1-1 Daigaku, Uchinada 920-0293, Japan.Phone: +81-76-286-2211 Ext.33206Fax: +81-76-286-3780E-mail: [email protected] WordsMarchiafava-Bignami diseaseMagnetic resonance imagingAlcohol consumption

Background: Thrombin is a critical protease modulating thrombosis as well as inflammation which are one of the main pathophysiological mechanisms in sickle vasculopathy, and its levels were reported to be high in sickle cell disease (SCD). The thrombin-thrombomodulin complex activates an inhibitor of fibrinolysis called TAFI acting by reducing plasmin affinity for its substrate hindering fibrinolysis. Objective: We aimed to determine the influence of the Thr325Ile single nucleotide polymorphism on TAFI antigen levels and potential effects on the severity of SCD in a cohort of Egyptian patients. Methods: Genotyping of Thr325lle polymorphism using Taq-Man SNP genotyping assay and TAFI level measurement using an Enzyme-Linked Immunosorbent Assay (ELISA) were performed for 80 SCD patients and 80 health control subjects. Results: Plasma TAFI levels were higher in SCD patients with Thr325Ile polymorphism, yet the difference was not statistically significant (p=0.204). SCD patients with polymorphic genotypes had a greater number of hospital admissions (p=0.03), Ten patients with acute chest syndrome had the homozygous polymorphic genotype (GG), and all patients with pulmonary hypertension had the polymorphic genotype (6 were homozygous [GG] and 5 were heterozygous [GA]). SCD patients complicated with pulmonary hypertension showed significantly higher plasma TAFI levels (p= 0.044). Conclusion: The analysis of Thr325Ile polymorphism combined with plasma TAFI level possibly suggests that the analyzed SNP could influence plasma levels and subsequently disease severity and hospitalization rate, which might be regarded as predictors for complex disease.

The Pd-catalyzed dipolar cycloaddition represents a significant synthetic strategy for the construction of useful heterocyclic com-pounds. This study developed the dipolar [4+2] and [6+2] cycloaddition reactions of benzo[d]isothiazole 1,1-dioxides (BDs) leading to the synthesis of BD-fused 1,3-oxazinane and 1,3-oxazocane derivatives, respectively. In particular, the synthesis of BD-fused 1,3-oxazinanes demonstrated regio- and enantioselective characteristics, resulting in products with good yields, enantioselectivity and regioselectivity (if applicable). Furthermore, the [6+2] cycloaddition reaction developed in this work represented the first strat-egy for the synthesis of medium-sized ring compounds based on BDs.

Obsessive-compulsive disorder (OCD) is a challenging psychiatric condition with limited treatment responses to standard therapies like selective serotonin reuptake inhibitors and cognitive-behavioral therapy. This letter to the Editor is intended to raise awareness within the scientific community about the potential use of N-acetylcysteine (NAC) as an alternative treatment, targeting the glutamatergic system dysfunctions and the inflammatory cytokines implicated in OCD. Preliminary studies suggest that NAC, at doses of 2,000-3,000 mg daily, can significantly alleviate OCD symptoms. Despite its promise and favourable safety profile, further research is imperative to establish optimal dosages and long-term efficacy. To date, the lack of suitable pharmaceutical forms with appropriate dosages hinders its empirical clinical application. In conclusion, NAC offers a potential adjunctive treatment for OCD, meriting more rigorous investigation.

The high curing temperatures required for traditional benzocyclobutene (BCB) materials have posed limitations on their applicability in high-temperature-sensitive fields. To address this challenge, our work focuses on the synthesis of a novel tetraphenylethylene (TPE)-functionalized BCB monomer, TPE-BCB, achieved through the introduction of an ether bond onto the BCB’s four-membered ring via Williamson reaction. TPE-BCB demonstrates remarkable low-temperature curing properties, characterized by a ring-opening peak temperature of 190 °C, representing a 25% reduction compared to conventional BCBs. Fully cured TPE-BCB resins exhibit exceptional dielectric and mechanical properties, coupled with minimal water absorption. Additionally, the incorporation of TPE with aggregation-induced emission (AIE) characteristics enhances the resins’ luminescence and photolithographic capabilities. Notably, our TPE-BCB resins achieve impressive photolithography performance with a resolution ratio of up to 10 µm. In contrast to conventional BCB-functionalized resins, TPE-BCB offers the dual advantage of low-temperature curing and luminescence. This development marks a significant step in the advancement of low-temperature curing BCB materials and serves as a pioneering example in the realm of multi-layer wafer bonding materials.

Background Due to changes in dietary habits tree nuts (TN) are consumed in many households and TN allergy appears to be increasing. One risk factor seems to be allergies to other food such as peanuts. The aim of our study was to investigate, how often peanut-sensitized infants and toddlers are co-sensitized to cashew, hazelnut and walnut and to determine the likelihood of its clinical relevance by their 2S albumin-specific (s)IgE. Methods Sera of 101 peanut-sensitized children, 5 to 24 months of age (median 16 months) were analyzed regarding sIgE to hazelnut, walnut and cashew and to their 2S-albumins Cor a 14, Jug r 1 and Ana o 3 as well as to Ara h 1 and 2, by using the NOVEOS TM immunoanalyzer system. Results 96% of the peanut-sensitized children were co-sensitized to at least one TN with 94.1% to hazelnut, 87.1% to walnut and 84.2% to cashew. More than half (58.4%) of the children were sensitized to at least one 2S albumin with similar rates for infants and toddlers, 26.7% to all three. Moreover, sensitization rates were similar in peanut allergic and tolerant children. Estimating the likelihood of clinical relevance, 15.8% of all peanut-sensitized children had an at least 90% probability to be hazelnut and/or cashew allergic. Conclusion TN sensitization seems to be common among peanut-sensitized infants and toddlers. Many had a high likelihood to be TN allergic. Therefore, it should be considered to determine TN-sIgE in peanut-sensitized children if TN are not consumed so far.

Leucism, in which pigmentation is lost over part or the entire body of an animal, has a range of possible genetic causes. Here, we report leucism in an individual tiger keelback (Rhabdophis tigrinus) found on Jeung Island, Shinan-gun, Jeollanam-do, South Korea, during a survey of the distribution of reptiles in the area. The individual was observed sunbathing in the bushes next to a pond. This individual exhibited ecdysis, thus it considered that have normal feeding activity. Our report represents the first observation of leucism in R. tigrinus, and thus, further analysis is needed of this phenotype to more clearly understand its impact on the species and its natural history.

Feathers comprise a series of evolutionary innovations but also harbor colour, a key biological trait known to co-vary with life history or complex traits. Those relationships are particularly true in melanin-based pigmentation species due to known pleiotropic effects of the melanocortin pathway – originating from melanin-associated phenotypes. Here we explore the molecular basis of melanin coloration and expected co-variation at the molecular level in the melanin-based, colour polymorphic system of the tawny owl (Strix aluco). An extensive body of literature has revealed that grey and brown tawny owl colour morphs differ in a series of life history and behavioral traits. Thus, it is plausible to expect co-variation also at molecular level between colour morphs. To investigate this possibility, we assembled the first draft genome of the species against which we mapped ddRADseq reads from 220 grey and 150 brown morphs - representing 10 years of pedigree data from a population in Southern Finland - and explored genome-wide associations with colour phenotype. Our results revealed putative molecular signatures of cold adaptation strongly associated with the grey phenotype, namely a non-synonymous substitution in MCHR1, plus 2 substitutions in non-coding regions of FTCD and FAM135A whose genotype combinations obtained a predictive power of up to 100% (predicting grey colour). These suggest molecular basis of cold environment adaptations predicted to be grey-morph specific. Our results potentially reveal part of the molecular machinery of melanin-associated phenotypes and provide novel insights towards understanding the functional genomics of colour polymorphism in melanin-based pigmented species.

Soils affect the distribution of hydrological processes by partitioning precipitation into different components of the water balance. Therefore, understanding soil-water dynamics at a catchment scale remains imperative to future water resource management. In this study the value of hydropedological insights to calibrate a processes based model. Soil morphology was used as soft data to assist in the calibration of the SWAT+ model at five different catchment sizes (48 km 2, 56 km 2, 174 km 2, 674 km 2 and 2421 km 2) in the Sabie River catchment, South Africa. The aim of this study was to calibrate the SWAT+ model to accurately simulate long-term monthly streamflow predictions as well as to reflect internal soil hydrological processes using a procedure focusing on hydropedology as a calibration tool in a multigauge system. Results indicated that calibration improved streamflow predictions where R 2 and Nash-Sutcliffe Efficiency (NSE) improved substantially, R 2 improved by 2 to 8% and NSE from negative correlations to values exceeding 0.5 at four of the five catchment scales compared to the uncalibrated model. Results confirm that soil mapping units can be calibrated individually within SWAT+ to improve the representation of hydrological processes. Particularly, the spatial linkage between hydropedology and hydrological processes, which is captured within the soil map of the catchment, can be adequately reflected within the model structure after calibration. This research should lead to an improved understanding of hydropedology as soft data to improve hydrological modelling accuracy.

The study aims to quantify the effect of Dufour number, on flow patterns and heat transfer rates in the exponentially accelerated vertical plate with MHD flow and chemical reaction. The unsteadiness of the flow suggests that time-dependent changes in velocity, temperature, and other relevant parameters are considered. MHD further complicates analysis with the electromagnetic interactions between the fluid and the field. The fluid, be characterized as a gray, absorbing/emitting radiation medium, indicating that it absorbs and emits thermal radiation but does not exhibit scattering behavior. Set of partial differential equations are then resolve using FEM. Graphical results are then discussed. Profiles vary with different, Dufour number, radiation, or temperature-dependent heat source/sink parameter. By varying the values of these governing parameters, on the skin-friction coefficient, Nusselt number, and Sherwood number are also analyzed.

INTRODUCTIONThe prognosis of adult relapse or refractory B cell acute lymphoblastic leukemia (r/r B-ALL) is dismal, with a complete remission rate of approximately 18%-44% if receiving salvage chemotherapy[1]. In recent years, immunotherapy represented by blinatumomab, inotuzumab ozogamicin (InO) and chimeric antigen T-cell (CART) therapy has demonstrated profound efficacy in r/r B-ALL[3-5]. However, those who have persistent positive measurable residual disease (MRD) still remain a high risk of relapse and poor outcome [2]. So far, only blinatumomab is approved for the treatment of MRD in B-ALL[4]. CD22 is detected to be expressed in more than 90% of B-ALL patients, indicating that CD22 is an ideal therapeutic target for B-ALL [6]. InO is an antibody-drug conjugate comprising a humanized anti-CD22 monoclonal antibody conjugate to calicheamicin. According to the INO-VATE study, significantly higher rate of complete remission was observed in r/r B-ALL patients who received InO monotherapy compared with traditional chemotherapy (73.8% vs 30.9%, P <0.0001) This encouranging data lead to the approvment of InO for the treatment of r/r B-ALL by the US Food and Drug Administration in 2017 [3]. Hitherto, the application of InO in the treatment of MRD has not been reported.

Coat colour and pattern are a distinguished feature in mammalian carnivores, shaped by climatic cycles and habitat type. It can be expressed in various ways, such as gradients, polymorphisms, and rare colour variants. Although natural selection explains much of the phenotypic variation found in the wild, genetic drift and heterozygote deficiency, as prominent in small and fragmented populations, may also affect phenotypic variability through the fixation of recessive alleles. The aim of this study was to test whether rare colour variants in the wild could relate to a deficiency of heterozygotes, resulting from habitat fragmentation and small population size. We present an overview of all rare colour variants in the order Carnivora, and compiled demographic and genetic data of the populations where they did and did not occur, to test for significant correlations. We also tested how phylogeny and body weight influenced the presence of colour variants with phylogenetic generalized linear mixed models (PGLMMs). We found 40 colour-variable species and 59 rare colour variants. In 17 variable phenotypic populations for which genetic diversity was available, the average AR was 4.18, HO = 0.59, and HE = 0.66, and FIS = 0.086. We found that variable populations displayed a significant reduction in heterozygosity and allelic richness compared to non-variable populations across species. We also found a significant negative correlation between population size and inbreeding coefficients. Therefore, it is possible that small effective size had phenotypic consequences on the extant populations. The high frequency of the rare colour variants (averaging 20%) also implies that genetic drift is locally overruling natural selection in small effective populations. As such, rare colour variants could be added to the list of phenotypic consequences of inbreeding in the wild.

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