Initial Rate Research Articles

Large Scale Ontology Matching System (LSMatch)

Background: Ontology matching provides a solution to the semantic heterogeneity problem by finding semantic relationships between entities of ontologies. Over the last two decades, there has been considerable development and improvement in the ontology matching paradigm. More than 50 ontology matching systems have been developed, and some of them are performing really well. However, the initial rate of improvement was measurably high, which now is slowing down. However, there still is room for improvement, which we as a community can work towards to achieve. Method: In this light, we have developed a Large Scale Ontology Matching System (LSMatch), which uses different matchers to find similarities between concepts of two ontologies. LSMatch mainly uses two modules for matching. These modules perform string similarity and synonyms matching on the concepts of the ontologies. Results: For the evaluation of LSMatch, we have tested it in Ontology Alignment Evaluation Initiative (OAEI) 2021. The performance results show that LSMatch can perform matching operations on large ontologies. LSMatch was evaluated on anatomy, disease and phenotype, conference, Knowledge graph, and Common Knowledge Graphs (KG) track. In all of these tracks, LSMatch’s performance was at par with other systems. Conclusion: Being LSMatch’s first participation, the system showed potential and has room for improvement.

Ester reduction on bifunctional metal-acid catalysts: Effect of metal to acid ratio

Ethers are highly desirable commodities in food, cosmetics, rubber, and coatings due to their low chemical reactivity, stability, and miscibility with other organic solvents. The direct reduction of esters to ethers by reactions with H2 provides a pathway to create nonsymmetrical ethers from biomass-derived esters. Propyl acetate (PA) and H2 react over platinum nanoparticles supported on Brønsted acidic faujasite zeolite (Pt-FAU) by two primary pathways: hydrogenation to form ethyl propyl ether and water and hydrogenolysis to form acetaldehyde and propanol. Here, we evaluate how rates and selectivities for these pathways depend on the ratios of the metal to Brønsted acid sites and the densities of Brønsted acid sites within Pt-FAU. X-ray absorption spectroscopy and infrared spectroscopy of adsorbed CO show that Pt species exist in a metallic state in the presence of H2 at elevated temperatures. The vibrational frequencies of chemisorbed CO on surface Pt atoms (Pts) do not vary significantly with differences in Pt contents or Brønsted acid site (H+) density. Temperature programmed reactions of amines protonated upon Brønsted acid sites demonstrate that the fractions of Brønsted acid sites accessible to organic reactants decrease with increasing Pt content, which implies intimate contact between Pt nanoparticles and acid sites. Comparisons between electron microscopy and rate measurements indicate that the proximity between Pt and H+ matters even when Pt nanoparticles appear to be within pores. Even though rates for reactions between PA and H2 over Pt-FAU decrease significantly during the initial use of the catalysts, analysis of initial rates provides mechanistic insight into elementary steps that determine rates. Initial hydrogenation rates increase by 13-fold, and hydrogenolysis rates increase by 33-fold when the atomic ratio of Pts to H+ increases from 0.08 to 0.6. Hydrogenation and hydrogenolysis rates increase with Pts density but do not correlate with H+ densities, which indicates kinetically relevant steps occur on Pt sites. These elementary steps likely involve the formation of hydrogenated intermediates (i.e., hemiacetal) that diffuse and react rapidly upon Brønsted acid sites, which generates intraparticle hemiacetal gradients. These correlations confirm that ester reduction rates and selectivities depend sensitively on the metal to acid ratio and proximity between these functions in a manner reminiscent of bifunctional catalysts used for hydroisomerization and hydrocracking catalysis. Consequently, increasing the number of stable Pt sites close to H+ sites should increase rates per mass catalyst by increasing the concentration of hemiacetals at Brønsted acid sites.

Targeting CD20-expressing malignant melanoma cells augments BRAF inhibitor killing.

Mutant BRAF targeted therapies remain a standard of care for the treatment of metastatic malignant melanoma (MM); however, high initial response rates are tempered by the persistence of residual MM cells that eventually lead to disease recurrence and mortality. As MM recurrence during targeted therapy can present with the simultaneous occurrence of multiple tumour nodules at the original body sites, we hypothesized the presence of an intrinsically resistant MM cell subpopulation. To identify an MM cell subpopulation that is intrinsically resistant to targeted therapy and possibly responsible for MM recurrence. Using melanoma cell lines, we defined culture conditions for the reproducible three-dimensional growth of melanospheres to investigate putative cancer stem cell populations. We undertook RNA sequencing and bioinformatic analysis to characterize cell populations between adherent and nonadherent culture, and cells expressing or not expressing CD20. Furthermore, we defined an in vitro assay to evaluate the killing of melanoma cancer stem cells as a therapeutic test using combination therapies targeting driver mutation and CD20. We described the culture conditions that promote MM cells to form melanospheres with a reproducible colony-forming efficiency rate of 0.3-1.3%. RNA sequencing of melanosphere vs. conventional MM cell cultures (n = 6), irrespective of the BRAF mutation status, showed that melanosphere formation was associated with growth and differentiation transcriptional signatures resembling MM tumours. Importantly, melanosphere formation also led to the emergence of a CD20+ MM cell subpopulation, similar to that observed in primary human MM tumours. CD20+ MM cells were resistant to BRAF inhibitor therapy and, consistent with this finding, demonstrated a Forkhead box protein M1 transcriptomic profile (n = 6). Combining BRAF inhibitor and anti-CD20 antibody treatment led to the additional killing of previously resistant CD20+ BRAF mutant MM cells. In patients with MM that harbour a CD20+ subpopulation, combined therapy with BRAF inhibitor and anti-CD20 antibody could potentially kill residual MM cells and prevent disease recurrence.

Benefits to Clinicians of Nonpharmacological Distraction During Pediatric Medical Procedure.

Nonpharmacologic distraction (NPD) during medical procedures in children is known to be beneficial to patients; however, no reviews have assessed their benefits to medical providers. We aimed to assess the benefits of NPD to medical providers. We searched 5 databases for relevant articles. Peer-reviewed published randomized controlled trials comparing NPD with standard care that included children who had undergone medical procedures were included. Primary outcomes were procedure time, number of medical staff involved, and initial success rate of venipuncture. Two reviewers assessed the risk of bias by using the Cochrane Collaboration (Oxford, United Kingdom)'s Randomized Controlled Trials Risk of Bias Tool, and we performed a meta-analysis to assess efficacy. We included 22 trials with 1968 participants. The main NPD was audiovisual distraction, such as tablets. No significant difference was found in venipuncture procedure time (mean difference: -9.79; 95% confidence interval: -22.38 to 2.81; low certainty). We found no studies on the number of medical staff. Our review did not find any clear NPD-associated benefit for the medical provider. The review included a small amount of literature, analyzed a small number of cases, and had a low certainty of evidence regarding procedure duration; therefore, further studies are needed to conclude the benefits to clinicians of NPD.

CHANGING THERAPY TO ACHIEVE ENDOSCOPIC HEALING IN ASYMPTOMATIC PATIENTS WITH IBD: WHEN IS PERFECT THE ENEMY OF GOOD?

Abstract INTRODUCTION The treat-to-target strategy for inflammatory bowel disease (IBD) recommends optimizing or changing therapy in patients who have not achieved clinical remission and endoscopic healing. In asymptomatic patients, the potential benefit of changing therapy to achieve endoscopic healing is less clear, particularly since <40% typically achieve endoscopic healing with current therapy. We sought to define appropriateness of changing therapy in asymptomatic IBD patients with active endoscopic inflammation. METHODS Using the RAND/UCLA Appropriateness Method, a panel of 9 IBD specialists considered appropriateness of changing therapy in 16 scenarios of patients with ulcerative colitis (UC) and 96 scenarios of Crohn’s disease (CD), rating them on a 9-point Likert scale as inappropriate (1-3), uncertain (4-6), or appropriate (7-9). Patients in all scenarios were asymptomatic with active endoscopic disease; variables included disease extent, behavior, prior treatment, recent disease progression, and prior disease complications. Current therapy was assumed to be optimized, so the only options were changing therapy or continuing current therapy. An additional 14 scenarios explored whether age >65 years and the possibility of pregnancy within the next year influenced treatment decision-making. Initial ratings were collected via online anonymous survey, discussed at an in-person meeting, and collected as final ratings in a second anonymous survey using a modified Delphi approach. Disagreement was assessed using a validated index. RESULTS Panelists rated it appropriate to change therapy (i.e., expected benefit sufficiently exceeds expected negative consequences) in 96/126 scenarios, generally those with progressive, complicated, and/or extensive disease; 27 scenarios of patients with mild and/or stable disease were rated uncertain, particularly in those with prior exposure to ≥3 drug classes (Table). Changing therapy in asymptomatic patients was rated inappropriate in three scenarios: in patients with UC Mayo 1 disease previously treated with ≥3 therapy classes with no endoscopic progression in the last year; in any patient who showed endoscopic improvement over the last year; and in any patient with CD who had only scattered aphthous ulcers. Patient age >65 years influenced a decision to change therapy specifically for anti-TNFs and JAK inhibitors; the possibility of pregnancy also influenced decision-making. Despite variability in ratings, the threshold for disagreement was not crossed for any scenario. CONCLUSIONS Our panel of IBD specialists rated appropriateness of changing therapy to achieve endoscopic healing in asymptomatic patients with UC and CD in a variety of scenarios. Our findings can be used to help guide clinical decision-making in this population until data from ongoing randomized studies are available (NCT05230173).

Organophosphate Esters in Building Materials from China: Levels, Sources, Emissions, and Preliminary Assessment of Human Exposure.

Source characteristics and health risks of indoor organophosphate esters (OPEs) are limited by the lack of knowledge on emission processes. This study attempted to integrate the contents and emissions of OPEs from indoor building materials to assess human health effects. Thirteen OPEs were investigated in 80 pieces of six categories of building materials. OPEs are ubiquitous in the building materials and ∑13OPE contents varied significantly (p < 0.05) from 72.8 ng/g (seam agent) to 109,900 ng/g (wallpaper). Emission characteristics of OPEs from the building materials were examined based on a microchamber method. Depending on the sample category, the observed initial area-specific emission rates of ∑13OPEs varied from 154 ng/m2/h (carpet) to 2760 ng/m2/h (wooden floorboard). Moreover, the emission rate model was developed to predict the release levels of individual OPEs, quantify source contributions, and assess associated exposure risks. Source apportionments of indoor OPEs exhibited heterogeneities in multiple environmental media. The joint OPE contribution of wallpaper and wooden floorboard to indoor dust was up to 94.8%, while latex paint and wooden floorboard were the main OPE contributors to indoor air (54.2%) and surface (76.1%), respectively. Risk assessment showed that the carcinogenic risks of tris(2-chloroethyl) phosphate (3.35 × 10-7) were close to the acceptable level (1 × 10-6) and deserved special attention.

Reaction Kinetics using a Chemputable Framework for Data Collection and Analysis

AbstractAutomated chemistry platforms have been widely explored, but many focus on fixed tasks for chemical synthesis or analysis. However, a typical synthetic chemistry workflow utilizes both, such as kinetic measurements for reaction development and optimization. Due to their repetitive and time‐consuming nature, kinetic measurements are often omitted, which limits the mechanistic investigation of reactions. Herein, we present a “Chemputer” platform with on‐line analytics (UV/Vis, NMR) which automates routine kinetic measurements. The system's capabilities are showcased by exploring an inverse electron‐demand Diels–Alder using initial rate measurements, a metal complexation using variable time normalization analysis (VTNA), and formation of a series of tosylamide derivatives using Hammett analysis. Over 60 individual experiments are presented which required minimal intervention, highlighting the significant time savings of automation. Owing to the modular design of the platform, which facilitates rapid integration of commercial analytical tools, our approach is widely accessible and adjustable to the reaction under investigation. The platform is operated using the chemical programming language, XDL, hence experimental procedures and results are stored in a precise, computer‐readable format. We propose that widespread adoption of this reporting protocol in the chemical community could build a database of validated kinetic data beneficial for Machine Learning.

Reaction Kinetics using a Chemputable Framework for Data Collection and Analysis.

Automated chemistry platforms have been widely explored, but many focus on fixed tasks for chemical synthesis or analysis. However, a typical synthetic chemistry workflow utilizes both, such as kinetic measurements for reaction development and optimization. Due to their repetitive and time-consuming nature, kinetic measurements are often omitted, which limits the mechanistic investigation of reactions. Herein, we present a "Chemputer" platform with on-line analytics (UV/Vis, NMR) which automates routine kinetic measurements. The system's capabilities are showcased by exploring an inverse electron-demand Diels-Alder using initial rate measurements, a metal complexation using variable time normalization analysis (VTNA), and formation of a series of tosylamide derivatives using Hammett analysis. Over 60 individual experiments are presented which required minimal intervention, highlighting the significant time savings of automation. Owing to the modular design of the platform, which facilitates rapid integration of commercial analytical tools, our approach is widely accessible and adjustable to the reaction under investigation. The platform is operated using the chemical programming language, XDL, hence experimental procedures and results are stored in a precise, computer-readable format. We propose that widespread adoption of this reporting protocol in the chemical community could build a database of validated kinetic data beneficial for Machine Learning.

The Aha! experience is associated with a drop in the perceived difficulty of the problem.

The study investigated the correlation between the intensity of the Aha! experience and participants' subjective difficulty ratings of problems before and after finding their solutions. We assumed that the Aha! experience arises from a shift in processing fluency triggered by changing from an initially incoherent problem representation to a coherent one, which ultimately leads to the retrieval of a solution with unexpected ease and speed. First, we hypothesized that higher Aha! experience ratings would indicate more sudden solutions, manifesting in a reduced correlation between the initial difficulty ratings and solution times. Second, we hypothesized that higher Aha! experience ratings would correspond to a greater shift in the subjective difficulty ratings between the initial and retrospective assessments. To test our hypotheses, we developed a novel set of rebus puzzles. A total of 160 participants solved rebuses and provided initial (within 5 s of problem presentation) and retrospective difficulty ratings (following the generation or presentation of a correct solution). They also rated their Aha! experience (after solution generation or presentation), confidence in solutions, and the likability of each rebus. Our findings revealed that the initial ratings of the problem's subjective difficulty were positively correlated with the solution time and that this correlation decreased in the case of a stronger Aha! experience. Aha! experience ratings were positively correlated with the differences between initial and retrospective difficulty ratings, confidence, solution accuracy, and rebus likability. We interpreted our results to be in line with the processing fluency and metacognitive prediction error accounts.

Removal of low concentration of perchlorate from natural water by quaternized chitosan sphere (CGQS): Efficiency and mechanism research

In this study, an innovative approach utilizing betaine as a raw material was employed to effectively modify the surface of chitosan with quaternary ammonium groups. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectrometer (FTIR) characterization showed that the quaternary ammonium groups on betaine were successfully loaded on the chitosan surface. The effects of dosage, pH, initial perchlorate concentration, temperature and co-existing anions on the removal efficiency of perchlorate were investigated. The saturated adsorption capacity of CGQS was 35.41 mg/g under natural condition. The impact of initial perchlorate concentrations and column flow rates on the column adsorption experiments were investigated, as well as natural water tests. Sterilizing performance experiments of CGQS were carried out innovatively. Under the condition of initial concentration of 0.5 mg/L, 9 BV/h (bed volume per hour), the effluent natural water was up to standard (≤0.07 mg/L) with a treatment capacity of 210 BV/g, and the sterilizing rate of CGQS was up to 97.02%. The proposed adsorption mechanisms involved surface pore adsorption, electrostatic adsorption of quaternary ammonium groups, and ion exchange between chloride and perchlorate ions. The CGQS prepared in this work had great potential for treating trace perchlorate contamination in natural water.

Design of lateral dynamic control objectives for multi-wheeled distributed drive electric vehicles

The lateral dynamic control system for electric vehicles aims to improve vehicle performance, making it critical to propose reasonable lateral dynamic control objectives. Therefore, in this study, a novel lateral dynamic control objectives is proposed for multi-wheeled distributed drive electric vehicles. Initially, utilizing the classical two-degrees-of-freedom (2DOF) vehicle model, two initial yaw rate references were established for handling characteristics of manoeuvrability and stability, respectively. The yaw rate references consider the vehicle velocity, steering wheel angle and road friction coefficient limitations. Considering the vital role of the sideslip angle in ensuring vehicle stability, a sophisticated weighting factor was developed based on a detailed analysis of the vehicle dynamics within the sideslip angle-sideslip angle rate phase plane. The weighting factor was determined based on the position of the vehicle state in the phase plane. This factor was adeptly applied to harmonise our dual control objectives, culminating in an integrated control aim that encapsulates the individual benefits of each. Finally, the lateral dynamic control objective was realised using a direct yaw moment control (DYC) system. The effectiveness of the proposed control objective was validated through hardware-in-the-loop (HIL) simulations.

Differences in the Residual Behavior of a Bumetrizole-Type Ultraviolet Light Absorber during the Degradation of Various Polymers.

The alteration of an ultraviolet light absorber (UVA: UV-326) in polymers (PP, HDPE, LDPE, PLA, and PS) over time during degradation was studied using an enhanced degradation method (EDM) involving sulfate ion radicals in seawater. The EDM was employed to homogeneously degrade the entire polymer samples containing the UVA. The PP and PS samples containing 5-phr (phr: per hundred resin) UVA films underwent rapid whitening, characterized by the formation of numerous grooves or crushed particles. Notably, the UVA loss rate in PS, with the higher glass transition temperature (Tg), was considerably slower. The behavior of crystalline polymers, with the exception of PS, was analogous in terms of the change in UVA loss rate over the course of degradation. The significant increase in the initial loss rate observed during EDM degradation was due to microplasticization. A similar increase in microplasticization rate occurred with PS; however, the intermolecular interaction between UVA and PS did not result in as pronounced an increase in loss rate as observed in other polymers. Importantly, the chemical structure of UVA remained unaltered during EDM degradation. These findings revealed that the primary cause of UVA loss was leaching from the polymer matrix.

Electrically Conductive Natural Rubber Composite Films Reinforced with Graphite Platelets.

Green natural rubber (NR) composites reinforced with synthetic graphite platelets, using alginate as a thickening and dispersing agent, were successfully developed to improve mechanical properties, chemical resistance, and electrical conductivity. The fabrication was performed using a latex aqueous microdispersion process. The research demonstrated the effective incorporation of graphite platelets into the NR matrix up to 60 parts per hundred rubbers (phr) without causing agglomeration or phase separation. Graphite incorporation significantly improved the mechanical strength of the composite films. NR with 60 phr of graphite exhibited the highest Young's modulus of 12.3 MPa, roughly 100 times that of the neat NR film. The reinforcement also strongly improved the hydrophilicity of the composite films, resulting in a higher initial water absorption rate compared to the neat NR film. Moreover, the incorporation of graphite significantly improved the chemical resistance of the composite films against nonpolar solvents, such as toluene. The composite films exhibited biodegradability at about 21% to 30% after 90 days in soil. The electrical conductivity of the composite films was considerably enhanced up to 2.18 × 10-4 S/cm at a graphite loading of 60 phr. According to the improved properties, the developed composites have potential applications in electronic substrates.

Slurry erosion behaviour of AlCoCrFeNi high entropy alloy coating prepared by atmospheric plasma spraying

ABSTRACT This study explores the application of AlCoCrFeNi high entropy alloy (HEA) coating on the SS316L steel using atmospheric plasma spraying to enhance durability in erosive environments. Annealing the coated sample at 650°C resulted in a uniform, dense coating with homogeneous HEA distribution, exhibiting a 16.2% improvement in microhardness compared to the pre-annealed coating. Slurry jet erosion testing revealed that under specific conditions (10 m s−1 impact velocity, 90° impingement angle and 10 wt-% slurry concentration), the annealed coating demonstrated a lower erosion rate. Increased velocity correlated with higher erosion rates due to augmented material removal, while normal angles exhibited lower erosion rates than oblique angles, emphasising plastic deformation over material removal. Initial erosion rate increases with slurry concentration were observed, followed by a decrease due to the protective effect of a slurry cloud at higher concentrations. Overall, the HEA-coated layer effectively safeguarded against erosive wear, particularly post-annealing, because of enhanced hardness.

Postoperative complications following neoadjuvant therapy and surgery in a phase 2 borderline resectable pancreatic cancer clinical trial (Alliance A021501).

664 Background: Postoperative complications in patients with borderline resectable pancreatic cancer treated with neoadjuvant therapy and pancreatectomy in the national cooperative group setting have not been previously characterized. Further, the impact of preoperative hypofractionated radiotherapy on postoperative outcomes is largely unknown. We sought to quantify perioperative morbidity among patients with pancreatic cancer who received neoadjuvant modified FOLFIRINOX chemotherapy with or without hypofractionated radiotherapy on a multicenter clinical trial. Methods: The A021501 phase 2 trial randomized patients with borderline resectable pancreatic ductal adenocarcinoma to 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX then hypofractionated radiotherapy (Arm 2), followed by pancreatectomy (Dec 31, 2016-Jan 1, 2019). Patients underwent resection according to defined operative standards at enrolling centers without specific requirements for either surgeon or hospital volume. Surgical complications and adverse events were assessed and captured at a single time point of 90 days after surgery and compared between treatment arms. Results: Of 126 enrolled patients, 51 (40%) underwent pancreatectomy (n=32, Arm 1; n=19, Arm 2) at 28 institutions. Vascular resection was performed in 19 patients (37%). One patient in Arm 2 died within 90 days after surgery. Rates of any surgical complication were 19% (n=6) in Arm 1 and 42% (n=8) in Arm 2 (p=0.07). Median length of stay was 7 days (range 5-38 days). Five (10%) patients required reoperation within 90 days. Readmission rates were higher in Arm 2 than Arm 1 (16% vs. 42%, p=0.04) but there were no differences in rates of reoperation, pancreatic fistula or abscess requiring drainage, or wound infection between study arms. 54% of patients (n=26/48) experienced a grade 3 or higher adverse event, with no difference between treatment arms (47% versus 67%, p=0.7). Rates of initiation of adjuvant therapy did not differ between treatment arms (66% vs. 68%, p=0.4). Pancreatic fistula and abscess were associated with adjuvant therapy (p&lt;0.01). No difference in overall survival was observed based on occurrence of surgical complications (HR 1.1; 95% CI 0.5-2.6). Conclusions: In this national cooperative group study of patients with borderline resectable pancreatic cancer,postoperative complications following neoadjuvant chemotherapy, radiation, and surgical resection were consistent with rates previously reported by high-volume institutions and using large datasets. Multimodality trials of preoperative therapy for locoregionally advanced pancreatic cancer may be safely performed in the cooperative group setting. Clinical trial information: NCT02839343 .

Improvement of the nutritional support management system for patients in intensive care units.

Nutritional support for patients hospitalized in the intensive care unit (ICU) is an important part of clinical treatment and care, but there are significant implementation difficulties. To introduce a modified nutritional support management system for ICU patients based on closed-loop information management and psychological counseling. The division of functions, personnel training, system construction, development of an intelligent decision-making software system, quality control, and improvement of the whole process were carried out to systematically manage nutritional support for ICU patients. Following the implementation of the whole process management system, the scores of ICU medical staff's knowledge, attitudes/beliefs, and practices regarding nutritional support were comprehensively enhanced. The proportion of hospital bed-days of total enteral nutrition (EN) in ICU patients increased from 5.58% to 11.46%, and the proportion of EN plus parenteral nutrition increased from 42.71% to 47.07%. The rate of EN initiation within 48 h of ICU admission increased from 37.50% to 48.28%, and the EN compliance rate within 72 h elevated from 20.59% to 31.72%. After the implementation of the project, the Self-rating Anxiety Scale score decreased from 61.07 ± 9.91 points to 52.03 ± 9.02 points, the Self-rating Depression Scale score reduced from 62.47 ± 10.50 points to 56.34 ± 9.83 points, and the ICU stay decreased from 5.76 ± 2.77 d to 5.10 ± 2.12 d. The nutritional support management system based on closed-loop information management and psychological counseling achieved remarkable results in clinical applications in ICU patients.

Does a simplified algorithm and integrated HCV care model improve linkage to care, retention, and cure among people who inject drugs? A pragmatic quality improvement randomized controlled trial protocol

BackgroundAs many as 2.4 million Americans are affected by chronic Hepatitis C Virus (HCV) in the United States.In 2018, the estimated number of adults with a history of HCV infection in San Diego County was 55,354 (95% CI: 25,411–93,329). This corresponded to a seroprevalence of 2.1% (95% CI: 2.1–3.4%). One-third of infections were among PWID. Published research has demonstrated that direct-acting antivirals (DAAs) have high efficacy and can now be used by primary care providers to treat HCV. In addition, limited evidence exists to support the effectiveness of simplified algorithms in clinical trial and real-world settings. Even with expanded access to HCV treatment in primary care settings, there are still groups, especially people who inject drugs (PWID) and people experiencing homelessness, who experience treatment disparities due to access and treatment barriers. The current study extends the simplified algorithm with a streetside ‘one-stop-shop’ approach with integrated care (including the offer of buprenorphine prescriptions and abscess care) using a mobile clinic situated adjacent to a syringe service program serving many homeless populations. Rates of HCV treatment initiation and retention will be compared between patients offered HCV care in a mobile clinic adjacent to a syringe services program (SSP) and homeless encampment versus those who are linked to a community clinic’s current practice of usual care, which includes comprehensive patient navigation.MethodsA quasi-experimental, prospective, interventional, comparative effectiveness trial with allocation of approximately 200 patients who inject drugs and have chronic HCV to the "simplified care" pathway (intervention group) or the "usual care" pathway (control group). Block randomization will be performed with a 1:1 randomization.DiscussionPrevious research has demonstrated acceptable outcomes for patients treated using simplified algorithms for DAAs and point-of-care testing in mobile medical clinics; however, there are opportunities to explore how these new, innovative systems of care impact treatment initiation rates or other HCV care cascade outcomes among PWID.Trial registrationWe have registered our study with ClinicalTrials.gov, a resource of the United States National Library of Medicine. This database contains research studies from United States and other countries around the world. Our study has not been previously published. The ClinicalTrials.gov registration identifier is NCT04741750.

Does patent pledge reduce pollution and carbon emissions? Evidence from China

The existing literature has extensively examined the impact of green innovations, such as patents, on pollution and carbon emissions. However, there has been comparatively less emphasis on the debt financing of green innovation by using patents as collateral. This oversight may have implications for the realization of pollution and carbon emissions reduction goals. Using a natural experiment based on the patent pledge pilot policy in China, this study investigates the impact of patent pledge on pollution and carbon emissions. We find that a significant reduction in the emissions of sulfur dioxide and carbon dioxide attributable to the patent pledge pilot policy, particularly in cities with lower initial green patent rates, and these results still hold after an array of robustness checks. We show that the encouragement of green innovation and the stimulation of environmental entrepreneurship are the mechanisms underlying these emission reduction effects. Furthermore, our analysis indicates that the impact of patent pledges on emission reduction is more pronounced in cities characterized by higher levels of government-reported environmental concern, public engagement in environmentally related searches, pollution information transparency indices, and green development evaluation indices.

The Cascade of Care for Early Infant Diagnosis in Zimbabwe: Point of Care HIV Testing at Birth and 6-8 Weeks.

Routine birth testing of HIV-exposed infants (HEI) using point of care (POC) nucleic acid testing may allow for earlier diagnosis and treatment of infants living with HIV, but more data are needed on retention in care for those diagnosed at birth and re-testing for those with a negative HIV birth test. POC birth testing (within 48 hours of birth) was offered to all HEI born at 10 public maternities in Zimbabwe from November 2018 to July 2019. Data were abstracted from routine registers, including information on re-testing at 6-8 weeks for infants testing HIV-negative at birth and 6-month retention in care among infants diagnosed with HIV at birth. Of 2854 eligible HEIs, 2806 (98.3%) received POC HIV birth testing. Thirty-nine infants with HIV were identified (1.4%), and 23 (59%) were started on antiretroviral therapy (ART). Twenty infants (51%) remained on ART at 6 months. Of the 2694 infants who tested negative at birth, 1229 (46.5%) had a documented retest at 6-8 weeks. 7 (0.6%) of those infants tested HIV-positive. The uptake of POC birth testing was high in study facilities, but low rates of ART initiation after a positive birth test, despite high retention on ART through 6 months, diminish the impact of POC birth testing and must be addressed. Among infants who tested negative at birth, rates of testing at 6-8 weeks of life (46%) were slightly lower than national rates of testing at the same age without a birth test (56%) during the study period. Improving infant HIV testing rates at 6-8 weeks, regardless of birth testing, should be a priority.

Erzhi pills reverse PD-L1-mediated immunosuppression in melanoma microenvironment

BackgroundCancer immunotherapies aimed at activating immune system, especially by blocking immune checkpoints, have become a successful modality for treating patients with advanced cancers. However, its clinical practice is frequently conceded by high outcomes, low initial response rates and severe side effects. New strategies are necessary to complement and advance this biological therapy. Erzhi Pills (EZP) have diverse pharmaceutical effects including immune regulation, anti-tumor and anti-senescence. We hypothesized that EZP could exert its antitumor effect through immunomodulation. PurposeThe aim of this study was to investigate the effects of EZP on anti-tumor activities, and define its molecular mechanisms. MethodsBy applying melanoma model with high immune infiltrates, we determined the anti-melanoma effect of EZP. To identify whether this effect was mediated by direct targeting tumor cells, cell viability and apoptosis were examined in vitro. Network pharmacology analysis was used to predict the potential mechanisms of EZP for melanoma via immune response. Flow cytometry, immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA) and crystal violet (CV) experiments were performed to detect T cell infiltrations and functions mediated by EZP. The mechanism of EZP was further investigated by western blotting both in vivo and in vitro. ResultsThe administration of EZP significantly inhibited tumor weight and volume. EZP extract could only slightly reduce cell viability and induce melanoma apoptosis. Network pharmacology analysis predicted that JAK-STAT signaling pathway and T cell receptor signaling pathway might be involved during EZP treatment. Flow cytometry and IHC analyses showed that EZP increased the number of CD4+ T cells and enhanced the function of CD8+ T cells. In co-culture experiments, EZP elevated killing ability of T cells. Western blotting showed that EZP treatment reduced PD-L1 signaling pathway. ConclusionThese findings indicated that EZP exerted anti-melanoma effects by inducing apoptosis and blocking PD-L1 to activate T cells. EZP might represent a promising candidate drug for cancer immunotherapies.