Glycopolymer with Sulfated Fucose and 6'-Sialyllactose as a Dual-Targeted Inhibitor on Resistant Influenza A Virus Strains.

The frequent mutations of influenza A virus (IAV) have led to an urgent need for the development of innovative antiviral drugs. Glycopolymers offer significant advantages in biomedical applications owing to their biocompatibility and structural diversity. However, the primary challenge lies in the design and synthesis of well-defined glycopolymers to precisely control their biological functionalities. In this study, functional glycopolymers with sulfated fucose and 6'-sialyllactose were successfully synthesized through ring-opening metathesis polymerization and a postmodification strategy. The optimized heteropolymer exhibited simultaneous targeting of hemagglutinin and neuraminidase on the surface of IAV, as evidenced by MU-NANA assay and hemagglutination inhibition data. Antiviral experiments demonstrated that the glycopolymer displayed broad and efficient inhibitory activity against wild-type and mutant strains of H1N1 and H3N2 subtypes in vitro, thereby establishing its potential as a dual-targeted inhibitor for combating IAV resistance.

Orthogonally woven 3D nanofiber scaffolds promote rapid soft tissue regeneration by enhancing bidirectional cell migration.

Repairing large-area soft tissue defects caused by traumas is a major surgical challenge. Developing multifunctional scaffolds with suitable scalability and favorable cellular response is crucial for soft tissue regeneration. In this study, we developed an orthogonally woven three-dimensional (3D) nanofiber scaffold combining electrospinning, weaving, and modified gas-foaming technology. The developed orthogonally woven 3D nanofiber scaffold had a modular design and controlled fiber alignment. In vitro, the orthogonally woven 3D nanofiber scaffold exhibited adjustable mechanical properties, good cell compatibility, and easy drug loading. In vivo, for one thing, the implantation of an orthogonally woven 3D nanofiber scaffold in a full abdominal wall defect model demonstrated that extensive granulation tissue formation with enough mechanical strength could promote recovery of abdominal wall defects while reducing intestinal adhesion. Another result of diabetic wound repair experiments suggested that orthogonally woven 3D nanofiber scaffolds had a higher wound healing ratio, granulation tissue formation, collagen deposition, and re-epithelialization. Taken together, this novel orthogonally woven 3D nanofiber scaffold may provide a promising and effective approach for optimal soft tissue regeneration.

Adherence, health care utilization, and costs between long-acting injectable and oral antipsychotic medications in South Carolina Medicaid beneficiaries with schizophrenia.

BACKGROUND: Schizophrenia and schizoaffective disorder require long-term antipsychotic treatment with antipsychotic medications, but poor medication adherence can lead to increased health care utilization and costs. Long-acting injectable antipsychotics (LAIs) offer potential therapeutic advantages in that they require less frequent dosing and improved medication adherence. South Carolina has the highest adoption of LAIs among US states, making it an ideal population for comparing the effectiveness of LAIs vs oral antipsychotics (OAPs) in treating schizophrenia or schizoaffective disorder. OBJECTIVE: To evaluate the effect of LAIs compared with OAPs on medication adherence, health care resource utilization, and costs among South Carolina Medicaid beneficiaries with schizophrenia or schizoaffective disorder. METHODS: South Carolina Medicaid beneficiaries with at least 1 claim for an LAI or OAP between January 1, 2015, and December 31, 2018, aged 18 to 65, with at least 2 claims with diagnoses of schizophrenia or schizoaffective disorder were included. Propensity scores (PSs) were calculated using logistic regression adjusting for confounders and predictors of the outcome. We estimated the "average treatment effect on the treated" by employing PS-weighted t-tests and chi-square tests. RESULTS: A total of 3,531 patients met the inclusion criteria, with 1,537 (44.5%) treated with LAIs and 1,994 (56.5%) treated with OAPs. In PS-weighted analyses, the LAI cohort had a greater proportion of days covered than the OAP cohort with a 365-day fixed denominator (69% vs 64%; P < 0.0001), higher medication possession ratio with a variable denominator while on therapy (85% vs 80%; P < 0.0001), and higher persistence (82% vs 64%; P < 0.0001). The average number of inpatient visits and emergency department visits did not significantly differ between cohorts (0.28 hospitalizations, P = 0.90; 3.68 vs 2.96 emergency department visits, P = 0.19). The number of outpatient visits, including visits for medication administration, were greater in the LAI cohort (23.1 [SD 24.2]) vs OAP (16.9 [SD 21.2]; P < 0.0001); however, including the costs for medication administration visits, outpatient costs (per member) were approximately $2,500 lower in the LAI cohort (P < 0.0001). The number of pharmacy visits was greater in the OAP cohort (LAI 21.0 [SD 17.0] vs OAP 23.0 [SD 15.0]; P = 0.006). All-cause total costs were greater in the LAI cohort ($26,025 [SD $29,909]) vs the OAP cohort ($17,291 [SD $25,261]; P < 0.0001) and were driven by the difference in pharmaceutical costs (LAI $15,273 [SD $16,183] vs OAP $4,696 [SD $10,371]; P < 0.0001). CONCLUSIONS: Among South Carolina Medicaid beneficiaries, treatment with LAIs for schizophrenia or schizoaffective disorder was associated with greater medication adherence rates. Patients using LAIs had higher drug costs and total costs, but lower outpatient and total nondrug costs compared with those using OAPs.

Nanopore-regulated in situ polymerization for synthesis of homogeneous heparan sulfate with low dispersity.

The biological activities of heparan sulfate (HS) are intimately related to their molecular weights, degree and pattern of sulfation and homogeneity. The existing methods for synthesizing homogeneous sugar chains of low dispersity involve multiple steps and require stepwise isolation and purification processes. Here, we designed a mesoporous metal-organic capsule for the encapsulation of glycosyltransferase and obtained a microreactor capable of enzymatically catalyzing polymerization reactions to prepare homogeneous heparosan of low dispersity, the precursor of HS and heparin. Since the sugar chain extension occurs in the pores of the microreactor, low molecular weight heparosan can be synthesized through space-restricted catalysis. Moreover, the glycosylation co-product, uridine diphosphate (UDP), can be chelated with the exposed metal sites of the metal-organic capsule, which inhibits trans-cleavage to reduce the molecular weight dispersity. This microreactor offers the advantages of efficiency, reusability, and obviates the need for stepwise isolation and purification processes. Using the synthesized heparosan, we further successfully prepared homogeneous 6-O-sulfated HS of low dispersity with a molecular weight of approximately 6 kDa and a polydispersity index (PDI) of 1.032. Notably, the HS generated exhibited minimal anticoagulant activity, and its binding affinity to fibroblast growth factor 1 was comparable to that of low molecular weight heparins.

Aberrant Super-Enhancer Landscape in Enzalutamide-Resistant Prostate Cancer Cells.

Background: Castration-resistant prostate cancer (CRPC), which has developed resistance to next-generation antiandrogens, such as enzalutamide (Enz), is a lethal disease. Furthermore, transcriptional regulation by super enhancers (SEs) is crucial for the growth and spread of prostate cancer, as well as drug resistance. The functions of SEs, a significant class of noncoding DNA cis-regulatory elements, have been the subject of numerous recent studies in the field of cancer research. Materials and Methods: The goal of this research was to identify SEs associated with Enz resistance in C4-2B cells using chromatin immunoprecipitation sequencing and cleavage under targets and tagmentation (CUT&Tag). Using HOMER analysis to predict protein/gene-binding motifs, we identified master transcription factors (TFs) that may bind to SE sites. Using small interfering RNA, WST-1 assays, and qRT-PCR, we then confirmed the associations between TFs of SEs and Enz resistance. Results: A total of 999 SEs were screened from C4-2B EnzR cells in total. Incorporating analysis with RNA-seq data revealed 41 SEs to be strongly associated with the promotion of Enz resistance. In addition, we finally predicted that master TFs bind to SE-binding regions. Subsequently, we selected zinc finger protein 467 (ZFP467) and SMAD family member 3 to confirm the functional connections of master TFs with Enz resistance through SEs (ZNF467). Conclusions: In this study, SMAD3 and ZNF467 were found to be closely related to Enz-resistant CRPC. Our research uncovered a sizable group of SEs linked to Enz resistance in prostate cancer, dissected the mechanisms underlying SE Enz resistance, and shed light on potential clinical uses for SEs.

Quercetin-Loaded Bioglass Injectable Hydrogel Promotes m6A Alteration of Per1 to Alleviate Oxidative Stress for Periodontal Bone Defects.

Periodontal disease ranks third among noncommunicable illnesses, behind cancer and cardiovascular disease, and is closely related to the occurrence and progression of various systemic diseases. However, elucidating the processes of periodontal disease and promoting periodontal bone regeneration remains a challenge. Here, quercetin is demonstrated to reduce the oxidative stress state of orofacial mesenchymal stem cells (OMSCs) in vitro and to affect the osteogenic growth of OMSCs through molecular mechanisms that mediate the m6A change in Per1. Nevertheless, the limited therapeutic efficacy of systemic medication and the limitations of local medication resulting from the small, moist, and highly dynamic periodontal environment make it challenging to treat periodontal tissues with medication. Herein, a biosafe injectable hydrogel drug-controlled delivery system is constructed as a bone-enhancing factory and loaded with quercetin to treat oxidative stress injury in periodontal tissues. This drug-carrying system made up of nanoscale bioglass microspheres and a light-cured injectable hydrogel, allows effective drug particle loading and cementation in the dynamic and moist periodontal environment. Furthermore, the system demonstrates the ability to stimulate OMSCs osteogenic differentiation in a Per1-dependent manner, which ultimately promotes periodontal bone repair, suggesting that this system has potential for clinical periodontal therapy.

A robust web-based tool to predict viral shedding in patients with Omicron SARS-CoV-2 variants.

Background: Data on viral kinetics and variants affecting the duration of viral shedding were limited. Our objective was to determine viral shedding in distinct severe acute respiratory syndrome coronavirus 2 variants, including Omicron BA.4/5 and BF.7, and to identify the relevant influencing factors. Methods: We carried out a longitudinal cohort study at Beijing Xiaotangshan Fangcang shelter hospital from May to June 2022 (Omicron BA.4/5) and from November to December 2022 (Omicron BF.7). Nucleocapsid protein (N) and open reading frame (ORF) genes were considered as the target genes of the reverse transcription PCR. The daily results of cycle threshold (CT), including lowest ORF1ab-CT values for days 1-3 post-hospitalisation and lowest N-CT values for days 1-3 post-hospitalisation (CT3minN) and demographic and clinical characteristics were collected. Results: 1433 patients with coronavirus disease 2019 (COVID-19) were recruited from the Fangcang shelter hospital, in which 278 patients were diagnosed with Omicron BA.4/5 and 1155 patients with Omicron BF.7. Patients with BF.7 infection showed a longer duration of viral shedding. The duration of viral shedding was associated with the variants age, alcohol use, the severity of COVID-19 and CT3minN. Moreover, the nomogram had excellent accuracy in predicting viral shedding. Conclusions: Our results indicated that patients with Omicron BF.7 had a longer period of contagiousness than those with BA.4/5. The duration of viral shedding was affected by a variety of factors and the nomogram may become an applicable clinical instrument to predict viral shedding. Furthermore, we developed a new COVID-19 viral shedding predicting model that can accurately predict the duration of viral shedding for COVID-19, and created a user-friendly website to apply this prediction model (https://puh3.shinyapps.io/CVSP_Model/).

Structural Elucidation of Glycosaminoglycans in the Tissue of Flounder and Isolation of Chondroitin Sulfate C.

Glycosaminoglycans (GAGs) are valuable bioactive polysaccharides with promising biomedical and pharmaceutical applications. In this study, we analyzed GAGs using HPLC-MS/MS from the bone (B), muscle (M), skin (S), and viscera (V) of Scophthalmus maximus (SM), Paralichthysi (P), Limanda ferruginea (LF), Cleisthenes herzensteini (G), Platichthys bicoloratus (PB), Pleuronichthys cornutus (PC), and Cleisthenes herzensteini (CH). Unsaturated disaccharide products were obtained by enzymatic hydrolysis of the GAGs and subjected to compositional analysis of chondroitin sulfate (CS), heparin sulfate (HS), and hyaluronic acid (HA), including the sulfation degree of CS and HS, as well as the content of each GAG. The contents of GAGs in the tissues and the sulfation degree differed significantly among the fish. The bone of S. maximus contained more than 12 µg of CS per mg of dry tissue. Although the fish typically contained high levels of CSA (CS-4S), some fish bone tissue exhibited elevated levels of CSC (CS-6S). The HS content was found to range from 10-150 ug/g, primarily distributed in viscera, with a predominant non-sulfated structure (HS-0S). The structure of HA is well-defined without sulfation modification. These analytical results are independent of biological classification. We provide a high-throughput rapid detection method for tissue samples using HPLC-MS/MS to rapidly screen ideal sources of GAG. On this basis, four kinds of CS were prepared and purified from flounder bone, and their molecular weight was determined to be 23-28 kDa by HPGPC-MALLS, and the disaccharide component unit was dominated by CS-6S, which is a potential substitute for CSC derived from shark cartilage.

Coupling Nano and Atomic Electric Field Confinement for Robust Alkaline Oxygen Evolution.

The alkaline oxygen evolution reaction (OER) is a promising avenue for producing clean fuels and storing intermittent energy. However, challenges such as excessive OH- consumption and strong adsorption of oxygen-containing intermediates hinder the development of alkaline OER. In this study, we propose a cooperative strategy by leveraging both nano-scale and atomically local electric fields for alkaline OER, demonstrated through the synthesis of Mn single atom doped CoP nanoneedles (Mn SA-CoP NNs). Finite element method simulations and density functional theory calculations predict that the nano-scale local electric field enriches OH- around the catalyst surface, while the atomically local electric field improves *O desorption. Experimental validation using in situ attenuated total reflection infrared and Raman spectroscopy confirms the effectiveness of the nano-scale and atomically electric fields. Mn SA-CoP NNs exhibit an ultra-low overpotential of 189 mV at 10 mA cm-2 and stable operation over 100 hours at ~100 mA cm-2 during alkaline OER. This innovative strategy provides new insights for enhancing catalyst performance in energy conversion reactions.

A sonication-filtration method for acquisition of integrated bacterial communities from phycosphere.

Bacteria in phycosphere engage in intricate interactions with microalgae by exchanging organic and inorganic matter. However, elucidating the primary roles of bacteria in phycosphere has been a big challenge, due to the lack of adequate methods for separating tightly associated bacteria from microalgal cells. In this study we evaluated several isolation methods including centrifugation, filtration, sonication combined with filtration, and tween lysis followed by sonication and filtration, aiming to efficiently acquire complete bacterial communities from phycosphere. The results demonstrated that the sonication-filtration approach maximally preserves the original characteristics of the bacterial communities. This method will facilitate the acquisition and further analysis of future experimental data.

Impact of Lianhua Qingwen on viral shedding in omicron mild/asymtomatic patients: a real-world study.

Background: Lianhuaqingwen (LHQW), a traditional Chinese medicine comprised of 13 herbal extracts renowned for their robust heat-clearing and detoxifying properties, has gained widespread utilization in China but has yet to garner similar recognition abroad. It is believed to exhibit efficacy in ameliorating symptoms in individuals afflicted with coronavirus disease 2019 (COVID-19). However, the precise impact of LHQW on viral shedding (VS), particularly in the context of mild or asymptomatic infections caused by the Omicron BF.4/5 or BF.7 variants of COVID-19, remained inadequately elucidated. Consequently, a real-world study was conducted, involving patients diagnosed with COVID-19, with the primary objective of ascertaining the effectiveness of LHQW in this specific clinical context. Methods: We conducted an investigation on Omicron-infected patients through a single-center, propensity score-matched real-world study conducted at Xiaotangshan Fangcang Hospital from May to November 2022. A total of 3,368 COVID-19 patients were enrolled in the study, all of whom presented mild or asymptomatic infections caused by either BF.4/5 or BF.7 strains of the virus. Demographic and clinical data were systematically collected from medical records. Patients were allocated to receive treatment with LHQW (designated as the treatment group) or received no LHQW treatment (designated as the not-treated/no-treatment group). Viral load was quantified utilizing quantitative real-time PCR (qPCR), and the duration of VS was defined as the time interval between the initial negative test result and the date of COVID-19 diagnosis or symptom onset. Results: The study encompassed a cohort of 3,368 patients, and following propensity score matching, a subset of 296 patients was meticulously chosen for subsequent analysis. Notably, baseline characteristics exhibited disparities between the treatment and not-treated/no-treatment groups. However, post-matching, these characteristics achieved a commendable level of comparability. Our findings unequivocally demonstrated that there existed no statistically significant disparity in VS. This holds true when comparing patients subjected to LHQW treatment against those not administered LHQW, as well as when contrasting individuals presenting asymptomatic and mild COVID-19 manifestations. Conclusion: No statistically significant difference in VS was observed between patients who underwent LHQW treatment and those who did not. Additional investigations are imperative to provide a comprehensive assessment of LHQW's efficacy, particularly in patients afflicted with severe COVID-19 or those infected with viral strains distinct from BF.4/5 or BF.7.

Natural Polymers - Based Hydrogel Dressings for Wound Healing.

SIGNIFICANCE: Acute wounds such as severe burns and chronic wounds like diabetic ulcers present a significant threat to human health. Wound dressings made from natural polymers offer inherent properties that effectively enhance wound healing outcomes and reduce healing time. RECENT ADVANCES: Numerous innovative hydrogels are being developed and translated to the clinic to successfully treat various wound types. This underscores the substantial potential of hydrogels in the future wound care market. Economically, annual sales of wound care products are projected to reach $15-22 billion by 2024. CRITICAL ISSUES: While chitosan-, cellulose-, and collagen-based hydrogel dressings are currently commercially available, scaling up and manufacturing hydrogels for commercial products remains a challenging process. Additionally, ensuring the sterility and stability of the chemical or biological components comprising the hydrogel are critical considerations. FUTURE DIRECTIONS: In light of the persistent increase in wound fatalities and the resulting economic and social impacts, as well as the importance of educating the public about dietary health and disease, there should be increased investment in new wound care dressings, particularly hydrogels derived from natural products. With numerous researchers dedicated to advancing preclinical hydrogels, the future holds promise for more innovative and more personalized hydrogel wound dressings.

Immune-enhancing activity of compound polysaccharide on the inactivated influenza vaccine.

Traditional Chinese medicine polysaccharides have numerous biological activities with broad applications in the biomedical industries. However, a clear understanding of the pharmacological activities of compound polysaccharides with multi-component structures remain challenging. This study aimed to investigate the immune boosting effect of compound polysaccharides on the influenza vaccine and assess the preliminary structure-activity relationship. The compound polysaccharide (CP) was isolated from the combined Chinese herbs lentinan, pachymaran and tremellan, and purified by gradient ethanol precipitation to obtain its subcomponents of CP-20, CP-40, CP-60, and CP-80 with decreasing molecular weights. These polysaccharides were mainly composed of glucans with different linkage patterns, including α-(1 â†’ 3)-glucan, α-(1 â†’ 4)-glucan and ß-(1 â†’ 6)-glucan. A significant improvement was observed in the survival of mice vaccinated with inactivated (IAV) vaccine and the isolated polysaccharides as adjuvants. A reduction in the pulmonary virus titer and weight loss were also observed. Moreover, CP-40 and CP-60, as well as the original CP, significantly enhanced the serum anti-IAV antibody titers and interleukin IL-2, IL-5, and IL-6 concentrations. These preliminary results indicate the immune boosting effect of the compound polysaccharides is highly relevant to the specific structural properties of the subcomponent, and CP-40 is worthy of further exploration as a glycan adjuvant for the IAV vaccine.

A Strain-Promoted Divergent Chemical Steroidation Unveils Potent Anti-Inflammatory Pseudo-Steroidal Glycosides.

The development of novel agents with immunoregulatory effects is a keen way to combat the growing threat of inflammatory storms to global health. To synthesize pseudo-steroidal glycosides tethered by ether bonds with promising immunomodulatory potential, we develop herein a highly effective deoxygenative functionalization of a novel steroidal donor (steroidation) facilitated by strain-release, leveraging cost-effective and readily available Sc(OTf)3 catalysis. This transformation produces a transient steroid-3-yl carbocation which readily reacts with O-, C-, N-, S-, and P-nucleophiles to generate structurally diverse steroid derivatives. DFT calculations were performed to shed light on the mechanistic details of the regioselectivity, underlying an acceptor-dependent steroidation mode. This approach can be readily extended to the etherification of sugar alcohols to enable the achievement of a diversity-oriented, pipeline-like synthesis of pseudo-steroidal glycosides in good to excellent yields with complete stereo- and regiospecific control for anti-inflammatory agent discovery. Immunological studies have demonstrated that a meticulously designed cholesteryl disaccharide can significantly suppress interleukin-6 secretion in macrophages, exhibiting up to 99% inhibition rates compared to the negative control. These findings affirm the potential of pseudo-steroidal glycosides as a prospective category of lead agents for the development of novel anti-inflammatory drugs.

High normal alanine aminotransferase is an indicator for better response to antiviral therapy in chronic hepatitis B.

Background: Evidence shows people living with CHB even with a normal ALT (40U/L as threshold) suffer histological disease and there is still little research to evaluate the potential benefit of antiviral benefits in them. Methods: We retrospectively examined 1352 patients who underwent liver biopsy from 2017 to 2021 and then obtained their 1-year follow-up data to analyze. Results: ALT levels were categorized into high and low, with thresholds set at >29 for males and >15 for females through Youden's Index. The high normal ALT group showed significant histological disease at baseline (56.43% vs 43.82%, p< 0.001), and better HBV DNA clearance from treatment using PSM (p=0.005). Similar results were obtained using 2016 AASLD high normals (male >30, female >19). Further multivariate logistic analysis showed that high normal ALT (both criterias) was an independent predictor of treatment (OR 1.993, 95% CI 1.115-3.560, p=0.020; OR 2.000, 95% CI 1.055-3.793, p=0.034) Both of the models had higher AUC compared with current scoring system, and there was no obvious difference between the two models (AUC:0.8840 vs 0.8835). Conclusion: Male >30 or female >19 and Male >29 or female>15 are suggested to be better thresholds for normal ALT. Having a high normal ALT in CHB provides a potential benefit in antiviral therapy.

Photocatalytic Generation of H2O2 Via a Hydrogen-Abstraction Pathway by Bi2.15WO6 under Visible Light.

Photocatalytic technology is a popular research area for converting solar energy into environmentally friendly chemicals and is considered the greenest approach for producing H2O2. However, the corresponding reactive oxygen species (ROS) and pathway involved in the photocatalytic generation of H2O2 by the Bi2.15WO6-glucose system are still not clear. Quenching experiments have established that neither •OH nor h+ contribute to the formation of H2O2, and show that the formed surface superoxo (≡Bi-OO•) and peroxo (≡Bi-OOH) species are the predominant ROS in H2O2 generation. In addition, various characterizations indicate the enhanced electron-transfer on the surface of Bi2.15WO6 with increasing contents of glucose via the ligand-to-metal charge transfer pathway, confirming H-transfer from glucose to ≡Bi-OO• or ≡Bi-OOH. The increased production of H2O2 with decreasing bond dissociation energy (BDEO-H) values of various phenolic compounds again supports the H-transfer mechanism from phenolic compounds to ≡Bi-OO• and then to ≡Bi-OOH. DFT calculations further reveal that on the Bi2.15WO6 surface, oxygen is sequentially reduced to ≡Bi-OO• and ≡Bi-OOH, while H-transfer from H2O or glucose to ≡Bi-OO• and ≡Bi-OOH, resulting in the production of H2O2. The lower energy barrier of H-transfer from adsorbed glucose (0.636 eV) than that from H2O (1.157 eV) indicates that H-transfer is more favorable from adsorbed glucose. This work gives new insight into the photocatalytic generation of H2O2 by Bi2.15WO6 in the presence of glucose/phenolic compounds via the H-abstraction pathway.

Enhanced Hydrogen Evolution Catalysis of Pentlandite due to the Increases in Coordination Number and Sulfur Vacancy during Cubic-Hexagonal Phase Transition.

The search for new phases is an important direction in materials science. The phase transition of sulfides results in significant changes in catalytic performance, such as MoS2 and WS2 . Cubic pentlandite [cPn, (Fe, Ni)9 S8 ] can be a functional material in batteries, solar cells, and catalytic fields. However, no report about the material properties of other phases of pentlandite exists. In this study, the unit-cell parameters of a new phase of pentlandite, sulfur-vacancy enriched hexagonal pentlandite (hPn), and the phase boundary between cPn and hPn are determined for the first time. Compared to cPn, the hPn shows a high coordination number, more sulfur vacancies, and high conductivity, which result in significantly higher hydrogen evolution performance of hPn than that of cPn and make the non-nano rock catalyst hPn superior to other most known nanosulfide catalysts. The increase of sulfur vacancies during phase transition provides a new approach to designing functional materials.

Evaluation of the diagnostic utility of metagenomic next-generation sequencing testing for pathogen identification in infected hosts: a retrospective cohort study.

Background: Metagenomic next-generation sequencing (mNGS) testing identifies thousands of potential pathogens in a single blood test, though data on its real-world diagnostic utility are lacking. Objectives: Determine the diagnostic utility of mNGS testing in practice and factors associated with high clinical utility. Design: Retrospective cohort study of mNGS tests ordered from June 2018 through May 2020 at a community teaching hospital. Methods: Tests were included if ordered for diagnostic purposes in patients with probable or high clinical suspicion of infection. Exclusions included patient expiration, hospice care, or transfer outside of the institution. Utility criteria were established a priori by the research team. Two investigators independently reviewed each test and categorized it to either high or low diagnostic utility. Reviewer discordance was referred to a third investigator. The stepwise multiple regression method was used to identify clinical factors associated with high diagnostic utility. Results: Among 96 individual tests from 82 unique patients, 80 tests met the inclusion criteria for analysis. At least one potential pathogen was identified in 58% of tests. Among 112 pathogens identified, there were 74 bacteria, 25 viruses, 12 fungi, and 1 protozoon. In all, 46 tests (57.5%) were determined to be of high diagnostic utility. Positive mNGS tests were identified in 36 (78.3%) and 11 (32.4%) of high and low diagnostic utility tests, respectively (p < 0.001). Antimicrobials were changed after receiving test results in 31 (67.4%) of high utility tests and 4 (11.8%) of low utility tests (p < 0.0001). In the multiple regression model, a positive test [odds ratio (OR) = 10.9; 95% confidence interval (CI), 3.2-44.4] and consultation with the company medical director (OR = 3.6; 95% CI, 1.1-13.7) remained significantly associated with high diagnostic utility. Conclusion: mNGS testing resulted in high clinical utility in most cases. Positive mNGS tests were associated with high diagnostic utility. Consultation with the Karius® medical director is recommended to maximize utility.

Evaluating the real world utility of using a diagnostic test that uses cell-free DNA to identify bacteria, viruses, fungi and protozoa from blood in hospitalized adult and pediatric patients Our institution has utilized a meta-genomic test that identifies bacteria, DNA-based viruses, fungi and protozoa from blood sample in hospitalized patients to support diagnostics in select clinical cases. We evaluated the utility of these tests in an adult and pediatric population. We found that 58% of the 96 tests from 82 unique patients produced a pathogen. Overall, a majority (58%) of tests were deemed to be of high utility which directly resulted in changes in antimicrobial therapy, selection of duration of therapy, direction for new diagnostics, or avoidance of further need for diagnostics. Positive tests and consultation with the medical director of the laboratory were both associated with high utility of the tests.

Rapid Initiation of Antiretroviral Therapy with Coformulated Bictegravir, Emtricitabine, Tenofovir Alafenamide Versus Efavirenz, Lamivudine and Tenofovir Disoproxil Fumarate in HIV-positive Men Who Have Sex with Men in China: Week 48 Results of the Multicenter, Randomized Clinical Trial.

BACKGROUND: Most international treatment guidelines recommend rapid initiation of antiretroviral therapy (ART) for people newly diagnosed with HIV-1 infection, but experiences with rapid ART initiation remain limited in China. We aimed to evaluate the efficacy and safety of efavirenz (400-mg) plus lamivudine and tenofovir disoproxil fumarate (EFV + 3TC + TDF) versus coformulated bictegravir, emtricitabine, tenofovir alafenamide (BIC/FTC/TAF) in rapid ART initiation among HIV-positive men who have sex with men (MSM). METHODS: This multicenter, open-label, randomized clinical trial enrolled MSM aged ≥18 years to start ART within 14 days of confirmed HIV diagnosis. The participants were randomly assigned in a 1:1 ratio to receive EFV(400-mg) + 3TC + TDF or BIC/FTC/TAF. The primary end point was viral suppression (<50 copies/ml) at 48 weeks per FDA Snapshot analysis. RESULTS: Between March 2021 and July 2022, 300 participants were enrolled; 154 were assigned to receive EFV + 3TC + TDF (EFV group) and 146 BIC/FTC/TAF (BIC group). At week 48, 118 (79.2%) and 140 (95.9%) participants in the EFV and BIC group, respectively, were retained in care with viral suppression; and 24 (16.1%) and 1 (0.7%) participant in the EFV and BIC group (p < 0.001), respectively, discontinued treatment due to adverse effects, death, or loss to follow-up. The median increase of CD4 count was 181 and 223 cells/µL (p = 0.020), respectively, for the EFV and BIC group, at week 48. The overall incidence of adverse effects was significantly higher for the EFV group (65.8% vs 37.7%, P < 0.001). CONCLUSION: BIC/FTC/TAF was more efficacious and safer than EFV(400-mg) + 3TC + TDF for rapid ART initiation among HIV-positive MSM in China.

An analysis of the relationship of triglyceride glucose index with gastric cancer prognosis: A retrospective study.

AIMS/INTRODUCTION: Gastric cancer, one of the most common malignant tumors worldwide, is affected by insulin resistance. The triglyceride glucose (TYG) index is considered a surrogate indicator of insulin resistance; however, its prognostic value in patients with gastric cancer remains obscure. This study aimed to determine whether the TYG index could predict the long-term prognosis of patients with gastric cancer after radical resection gastrectomy. MATERIALS AND METHODS: We retrospectively analyzed patients with gastric cancer who underwent radical resection gastrectomy. The preoperative TYG index was calculated using the patients' laboratory data. Patients were divided into two groups based on a high or low TYG index. We observed overall survival and evaluated the clinical application value of the index using Cox proportional hazards regression to calculate independent parameters. A prediction model was also established. RESULTS: In total, 822 patients with gastric cancer were included. The high and low TYG index groups comprised 353 and 469 patients, respectively. The overall survival time was significantly longer in the high-index group than in the low-index group. In the multivariate analysis, TYG index, preoperative age, surgical procedure, tumor node metastasis (TNM) stage, N stage, and postoperative complications (all p < 0.01) were considered independent prognostic predictors. Based on the multivariate analysis, the riglyceride glucose (TYG) index hazard ratio was 0.70 (95% confidence interval, 0.54-0.89, p = 0.004). CONCLUSIONS: We established a model with a high clinical application value and clinical practice relevance to predict the prognosis of gastric cancer. In this model, TYG was an independent protective factor for gastric cancer prognosis.