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Selective detection of disease-associated changes in the glycocalyx is an emerging field in modern targeted therapies. Detecting minor glycan changes on the cell surface is a challenge exacerbated by the lack of correspondence between cellular DNA/RNA and glycan structures. We demonstrate that multivalent displays of lectins on DNA-barcoded phages-liquid lectin array (LiLA)-detect subtle differences in density of glycans on cells. LiLA constructs displaying 73 copies of diCBM40 (CBM) lectin per virion (φ-CBM 73 ) exhibit non-linear ON/OFF-like recognition of sialoglycans on the surface of normal and cancer cells. A high-valency φ-CBM 290 display, or soluble CBM protein, cannot amplify the subtle differences detected by φ-CBM 73 . Similarly, multivalent displays of CBM and Siglec-7 detect differences in the glycocalyx between stem-like and non-stem populations in cancer. Multivalent display of lectins offer in situ detection of minor differences in glycocalyx in cells both in vitro and in vivo not feasible to currently available technologies., Competing Interests: Declaration of interests R.D. is shareholder of the start-up company 48Hour Discovery Inc. that licensed the patent application (WO2018141058A1) describing LiGA technology., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To evaluate surface roughness and bacterial adhesion after in situ biodegradation of the cementation interface of indirect restorations cemented with preheated resin composite., Methods and Materials: Resin composite blocks (Z250XT/3M ESPE) were cemented to bovine enamel (7 × 2.5 × 2 mm) using preheated microhybrid resin composites: (1) Filtek Z100 (3M ESPE) (Z100); (2) Gradia Direct X (GC America) (GDX); and (3) Light-cured resin cement RelyX Veneer (3M ESPE) (RXV) (n=21). The resin composites were preheated on a heating device (HotSet, Technolife) at 69°C for 30 minutes. Disk-shaped specimens (7 × 1.5 mm) were made for biodegradation analysis with the luting agents (n=25). The in situ phase consisted of 20 volunteers' using an intraoral palatal device for 7 days. Each device had six cylindrical wells for the blocks and the disk-shaped specimens. Biodegradation was evaluated through surface roughness (Ra), scanning electron microscopy (SEM) micromorphological analysis, and colony-forming unit (CFU) count. The film thickness of the luting agents was also measured under stereomicroscopy., Results: Increased surface roughness was observed after the cariogenic challenge without differences between the luting agents. Higher variation and surface flaws suggestive of particulate detachment were observed for Z100. No differences were observed in CFU counts., Conclusions: All materials underwent surface biodegradation, and the surface roughness of the resin cements was similar to or lower than that of the preheated resin composites. The resin composites' film thickness was thicker than that of the resin cement. Clinicians should be aware of these factors when choosing the use of preheated resin composite since it can lead to reduced longevity of the cementation interface and, therefore, restorations., (©Operative Dentistry, 2024.)

Statement of Problem: Cementation is one of the most critical steps that influence the failure rates of indirect restorations. Self-adhesive resin cements arose out of the need for technical simplification of this procedure to reduce the risk of operative errors, with good acceptance by clinicians. How the failure rate of indirect single-tooth restorations cemented with self-adhesive resin cements compares with the failure rate of those cemented conventionally is unclear., Purpose: The purpose of this systematic review and meta-analysis of randomized clinical trials was to compare self-adhesive resin cements versus conventional cements on the failure rates of indirect restorations., Material and Methods: The review was registered at the International Prospective Register of Systematic Reviews (PROSPERO - CRD42020215577). The search strategy was adapted for 5 databases (PubMed, The Cochrane Library, EMBASE, Web of Science, and LILACS) and 1 nonpeer-reviewed literature source (clinicaltrials.gov). The strategy was guided by the problem/population, intervention, comparison, outcome (PICO) question: adults indicated for indirect restorations -P, self-adhesive resin cement -I, conventional cement-C, failure rates-O. The risk of bias was assessed using the Cochrane risk of bias (RoB2) tool and guidelines. Meta-analysis merged the results from included studies by pooling the hazard ratios and standard errors, available or estimated. The certainty of evidence was assessed by using the classification of recommendations, evaluation, development, and evaluation (GRADE) approach., Results: Nine randomized clinical trials were included in qualitative and quantitative analysis. Eight studies detected nonsignificant differences in failure rates between cements. Only 1 study reported a significantly higher failure rate on single-tooth ceramic crowns luted with self-adhesive resin cement. Nonsignificant differences were detected after the results from all studies had been pooled., Conclusions: Based on clinical evidence, self-adhesive resin cements can be recommended for the cementation of indirect single-tooth restorations with a similar risk of failure to conventional cements., (Copyright © 2024 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Background: Uroflowmetry is a non-invasive examination considered as a first-line assessment for children with lower urinary tract symptoms (LUTS). Currently, the performance of two uroflowmetry tests is recommended by ICCS for all patients with LUTS. This study aims to evaluate the differences between two uroflowmetry tests in children with lower urinary tract symptoms and their impact on the patient's diagnostic workup and clinical outcome., Methods: Forty patients with LUTS, aged 4-17 years, were evaluated prospectively with two consecutive uroflowmetry tests and ultrasonography. They were classified based on the ICCS criteria for curve pattern and divided into two groups based on the SPU classification of fractionated (staccato and intermittent) and smooth (bell, tower and plateau). They were also separated into three groups based on estimated bladder capacity (voided volume + post-void residual on ultrasound): high (>115%), low (<60%) or normal capacity., Results: The mean age was 8 (IQR 6.0-10.0) years and 25 (62.5%) patients were female. There was an increase in nonbell-shaped curves from the first (32.5%) to the second test (52.5%). The curve shape between the uroflowmetries based on ICCS classification showed a Kappa value of 0.349 (fair). Classifying curves as fractionated or smooth yielded a Kappa value of 0.714 (substantial) (table). The Bland-Altman test showed disagreement in the parameter of time to Qmax. There was a significant difference in categorizing bladder capacity as high, low, or normal: it was concordant in 63.6% for high, 68.4% for normal and 50% for low capacity (p = 0.001)., Discussion: Despite the disagreement found classifying the curves based on the ICCS pattern, also demonstrated in other studies, there was a substantial agreement using the SPU criteria. It reinforces the greater reliability of the SPU system and it may be the key to reduce the subjectivity of uroflowmetry. Even though this classification being associated with a higher agreement in interpretation of the curves, repeating uroflowmetry does not present a clinically significant divergence that changes the patient's diagnostic workup. Our study is limited by the lack of EMG and larger sample., Conclusion: Considering the flow curve pattern, the agreement between two uroflowmetries was substantial according to the SPU and only reasonable by the ICCS classification. Regardless of some differences found between the flows, a second uroflowmetry test might not have clinical relevance that justifies its recommendation for all patients., (Copyright © 2024 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Asparagine is a non-essential amino acid crucial for protein biosynthesis and function, and therefore cell maintenance and growth. Furthermore, this amino acid has an important role in regulating several metabolic pathways, such as tricarboxylic acid cycle and the urea cycle. When compared to normal cells, tumor cells typically present a higher demand for asparagine, making it a compelling target for therapy. In this review article, we investigate different facets of asparagine bioavailability intricate role in malignant tumors raised from solid organs. We take a comprehensive look at asparagine synthetase expression and regulation in cancer, including the impact on tumor growth and metastasis. Moreover, we explore asparagine depletion through L-asparaginase as a potential therapeutic method for aggressive solid tumors, approaching different formulations of the enzyme and combinatory therapies. In summary, here we delve into studies about endogenous and exogenous asparagine availability in solid cancers, analyzing therapeutic implications and future challenges., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hepatosplenic schistosomiasis is a complex clinical condition caused by the complications of chronic infection with Schistosoma species that cause intestinal schistosomiasis. Hepatosplenic schistosomiasis derives from the fibrotic reaction stimulated around parasite eggs that are transported by the mesenteric circulation to the liver, causing periportal fibrosis. Portal hypertension and variceal gastrointestinal bleeding are major complications of hepatosplenic schistosomiasis. The clinical management of hepatosplenic schistosomiasis is not standardised and a parameter that could guide clinical decision making has not yet been identified. Transjugular intrahepatic portosystemic shunt (TIPS) appears promising for use in hepatosplenic schistosomiasis but is still reported in very few patients. In this Grand Round, we report one patient with hepatosplenic schistosomiasis treated with TIPS, which resulted in regression of oesophageal varices but had to be followed by splenectomy due to persisting severe splenomegaly and thrombocytopenia. We summarise the main challenges in the clinical management of this patient with hepatosplenic schistosomiasis, highlight results of a scoping review of the literature, and evaluate the use of of TIPS in patients with early hepatosplenic schistosomiasis, to improve the prognosis., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

American Bullfrogs, Aquarana catesbeiana, are invasive anuran species distributed worldwide. One of the adverse impacts that this species causes in native communities is as a reservoir host for pathogens and parasites. Here, we report the coinfection of two pathogenic organisms in A. catesbeiana: Ranavirus and the nematode Eustrongylides. Bullfrogs were collected in the wild in a pond close to the urban area of São Paulo, Brazil. The prevalence of both pathogens was high: 77% were infected with ranavirus with a mean viral load of 1010.3 viral copies, and 100% of the bullfrogs were infected by Eustrongylides sp. with a mean intensity of infection of 13.4 specimens per host. Four host specimens (31%) presented pathological signs that seemed to be related to the Eustrongylides sp. infection, such as internal organs adhered to each other due to high intensity and large size of the nematodes, ulcers, and raw flesh wounds caused by the nematode. The pathogenic and concomitant infections have potential zoonotic implications and raise concerns about human infection risks for Eustrongylides infection. Moreover, such infections may represent an additional level of threat to native communities through the potential shifts in patterns of parasite and pathogen transmission. Future research involving the native anuran community is essential to ascertain whether invasive bullfrogs are attenuating or exacerbating diseases such as ranavirosis and eustrongylidiosis., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Acute lymphoblastic leukaemia is currently treated with bacterial L-asparaginase; however, its side effects raise the need for the development of improved and efficient novel enzymes. Previously, we obtained low anti-asparaginase antibody production and high serum enzyme half-life in mice treated with the P40S/S206C mutant; however, its specific activity was significantly reduced. Thus, our aim was to test single mutants, S206C and P40S, through in vitro and in vivo assays. Our results showed that the drop in specific activity was caused by P40S substitution. In addition, our single mutants were highly stable in biological environment simulation, unlike the double-mutant P40S/S206C. The in vitro cell viability assay demonstrated that mutant enzymes have a higher cytotoxic effect than WT on T-cell-derived ALL and on some solid cancer cell lines. The in vivo assays were performed in mice to identify toxicological effects, to evoke immunological responses and to study the enzymes' pharmacokinetics. From these tests, none of the enzymes was toxic; however, S206C elicited lower physiological changes and immune/allergenic responses. In relation to the pharmacokinetic profile, S206C exhibited twofold higher activity than WT and P40S two hours after injection. In conclusion, we present bioengineered E. coli asparaginases with high specific enzyme activity and fewer side effects.

Thermostability is an important and desired feature of therapeutic proteins and is critical for the success or failure of protein drugs development. It can be increased by PEGylation-binding of poly(ethylene glycol) moieties-or glycosylation-post-translational modification to add glycans. Here, the thermostability and thermodynamic parameters of native, PEGylated, and glycosylated versions of the antileukemic enzyme crisantaspase were investigated. First-order kinetics was found to describe the irreversible deactivation process. Activation energy of the enzyme-catalyzed reaction ( E *) was estimated for native, PEGylated, and glycosylated enzyme (10.2, 14.8, and 18.8 kJ mol -1 respectively). Half-life decreased progressively with increasing temperature, and longer half-life was observed for PEG-crisantaspase (87.74 min) at 50 °C compared to the native form (9.79 min). The activation energy of denaturation of PEG-crisantaspase (307.1 kJ mol -1 ) was higher than for crisantaspase (218.1 kJ mol -1 ) and Glyco-crisantaspase (120.0 kJ mol -1 ), which means that more energy is required to overcome the energy barrier of the unfolding process. According to our results, PEG-crisantaspase is more thermostable than its native form, while Glyco-crisantaspase is more thermosensitive.

The pink sugarcane mealybug Saccharicoccus sacchari (Cockerell, 1895) (Hemiptera: Pseudococcidae) occurs practically in all sugarcane producing regions Saccharum spp. (Poaceae) causing damage. Little information is available about insect's biology under Brazilian conditions. In this work, biological development of pink sugarcane mealybug was studied at temperatures of 23 °C ± 2 °C and 28 °C ± 2 °C without photophase and relative humidity of 80%. Number and viability of eggs, incubation time, duration of the last oviposition, duration of each nymphal instar, viability of the nymphs, start of oviposition and longevity of the females were recorded. Biological development of insects was stipulated by the SAS University Edition software, version 9.4. There were differences in the life cycle of the pseudococcid at both temperatures evaluated. Females of S. sacchari had three nymphal instars and reproduce asexually. Asexual reproduction occurs in the field and under controlled conditions. By increasing the temperature increases, insect lived longer and the presence of the winged male in Brazil indicates the possibility of sexual reproduction of the species.

Background: Limited long-term safety data are published on HA/CaHA/L, a hybrid dermal filler combining hyaluronic acid (HA), calcium hydroxyapatite (CaHA), and lidocaine (L)., Methods: This retrospective multicenter study assessed treatment-emergent adverse events (TEAEs) in adults treated with HA/CaHA/L. The full analysis set (FAS) included eligible consented adults ( N  = 403); the long-term safety analysis (LTSA) set included FAS participants with greater than or equal to 12-months HA/CaHA/L exposure ( n  = 243)., Results: Participants were majority female (94.0%), with Fitzpatrick skin phototypes II/III (80.1%) and a mean age of 50.1 years. Most participants (86.4%) received one HA/CaHA/L treatment. The median time between participants' first HA/CaHA/L treatment and chart review was 15.4 months. Participants received a mean of 2.2 mL (0.5-8.9 mL) filler per treatment. Treated areas were predominantly malar (71.2%) and mandible (69.7%) regions. Most participants (95.0%) had one or more aesthetic treatments other than HA/CaHA/L [eg, other dermal fillers (84.1%), botulinum toxin (63.3%)]. Nineteen (4.7%) FAS participants had 20 documented TEAEs; most (3.5%, n  = 14 participants) were mild in severity. Twelve TEAEs in 11 participants (2.7%) were related to HA/CaHA/L: induration (three, 0.7%), edema (3, 0.7%), and implant site nodules (five, 1.2%), which were noninflammatory and likely related to product placement. Among the LTSA, 15 (6.2%) participants had 16 documented TEAEs (six edema, five implant site nodules, one inflammation, three skin induration, one hypersensitivity); most were mild in severity. Nine TEAEs in eight participants (3.3%) were HA/CaHA/L-related. No treatment-emergent serious AEs were reported., Conclusion: The data from this noninterventional retrospective study support the favorable longer term (>12 month) safety profile of HA/CaHA/L., Competing Interests: Braz is an investigator and advisory board member for Allergan Aesthetics, an AbbVie company. Colucci is an investigator, speaker, and consultant for Allergan Aesthetics, an AbbVie company. Macedo de Oliveira, Monteiro, Ormiga, and Wanick are investigators, speakers, and advisory board members for Allergan Aesthetics, an AbbVie company. Cazerta, Kerson, Musumeci, and Silberberg are full-time employees of AbbVie Inc and may own AbbVie stock. Allergan Aesthetics, an AbbVie Company, funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Sarah J. Cross, PhD, of AbbVie Inc. and editorial support was provided by Angela T. Hadsell of AbbVie Inc.; both were funded by AbbVie Inc., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Ultraviolet (UV) radiation from sunlight can damage DNA, inducing mutagenesis and eventually leading to skin cancer. Topical sunscreens are used to avoid the effect of UV irradiation, but the topical application of DNA repair enzymes, such as photolyase, can provide active photoprotection by DNA recovery. Here we produced a recombinant Thermus thermophilus photolyase expressed in Escherichia coli, evaluated the kinetic parameters of bacterial growth and the kinetics and stability of the enzyme. The maximum biomass (𝑋 𝑚𝑎𝑥 ) of 2.0 g L -1 was reached after 5 h of cultivation, corresponding to 𝑃 X  = 0.4 g L -1 h. The µ 𝑚𝑎𝑥 corresponded to 1.0 h -1 . Photolyase was purified by affinity chromatography and high amounts of pure enzyme were obtained (3.25 mg L -1 of cultivation). Two different methods demonstrated the enzyme activity on DNA samples and very low enzyme concentrations, such as 15 µg mL -1 , already resulted in 90% of CPD photodamage removal. We also determined photolyase k M of 9.5 nM, confirming the potential of the enzyme at very low concentrations, and demonstrated conservation of enzyme activity after freezing (-20°C) and lyophilization. Therefore, we demonstrate T. thermophilus photolyase capacity of CPD damage repair and its potential as an active ingredient to be incorporated in dermatological products., (© 2024 Wiley-VCH GmbH.)