High Response Research Articles

Emerging detection of carbon-based gases with multiple bonds by activating Mo[dbnd]O bonding in Na, Sb-codoped NiMoO4

Exhausting carbon-based gases from building construction or comfortable household supplies have caused the main pollution gas species for the indoor air environment. Given the variety of indoor activities, many reports have been challenged to find room-temperature operational and harmless materials. Here, we report that the activating MoO vibration mode in Na,Sb doped-NiMoO4 micro-sized powder reveals the high response of CO and VOC, occupying multiple bonds at room temperature. We performed Na and Sb doping in the α-NiMoO4 crystal structure, such as introducing the Sb in Ni and interstitial doping of Na in around 4 Å of free space in the NiMoO4 crystal structure that manipulates the partial β-NiMoO4 phase. The Na,Sb-codoped NiMoO4 generates the higher MoO vibration mode from FT-IR measurement and enables carbon-based gas detection with 38 responses to CO and nearly 20 responses to VOC under 20 ppm of each analyte gases environment. Furthermore, the n-type gas sensing behavior of Na,Sb doped-NiMoO4 chemiresistor exhibits an immediate sensing response instead of a none-of response than intrinsic or single element doped NiMoO4. These results suggest that Na,Sb codoped-NiMoO4 is the applicable material for emergent warning against carbon-based gas exposure in the indoor environment. In addition, activating the electrochemical reaction site of MoO4–2 in NiMoO4 is tailorable by a simple doping process.

Efficacy of thrombopoietin receptor agonists versus rituximab in non-responsive immune thrombocytopenia-A single centre retrospective analysis.

Management of immune thrombocytopenia (ITP) beyond initial glucocorticoid therapy is challenging. In this retrospective single-centre cohort study, we compared all ITP patients relapsed or non-responsive to glucocorticoid therapy treated with either continuous TPO-RAs (n = 35) or rituximab induction (n = 20) between 2015 and 2022. While both groups showed high initial complete response rates (CR, 68.6 vs. 80.0%, ns), the overall rate of progression to the next therapy was higher after time-limited rituximab (75.0 vs. 42.9%), resulting in a lower relapse-free survival (median 16.6 vs. 25.8 months, log-rank; p < 0.05). We conclude that both treatments show similar initial efficacy and their ideal duration of therapy warrants further investigation.

Efficacy of thrombopoietin receptor agonists versus rituximab in non-responsive immune thrombocytopenia-A single centre retrospective analysis.

Management of immune thrombocytopenia (ITP) beyond initial glucocorticoid therapy is challenging. In this retrospective single-centre cohort study, we compared all ITP patients relapsed or non-responsive to glucocorticoid therapy treated with either continuous TPO-RAs (n = 35) or rituximab induction (n = 20) between 2015 and 2022. While both groups showed high initial complete response rates (CR, 68.6 vs. 80.0%, ns), the overall rate of progression to the next therapy was higher after time-limited rituximab (75.0 vs. 42.9%), resulting in a lower relapse-free survival (median 16.6 vs. 25.8 months, log-rank; p < 0.05). We conclude that both treatments show similar initial efficacy and their ideal duration of therapy warrants further investigation.

A DECOUPLED MAGNETIC INTEGRATION TECHNIQUE FOR DUAL-FREQUENCY TOPOLOGIES

The dual-frequency converter comprises a high-frequency buck unit and a low-frequency buck unit, which has the advantages of high efficiency and fast dynamic response. But also, the increase of magnetic parts leads to the power density of the converter being greatly reduced; for this problem, this paper proposes a three-section winding method to decouple the two inductors in the converter integrated into a magnetic core, given the integrated magnetic parts structure and establish its gyrator-capacitor model to derive the decoupling conditions. The flux density distribution of the magnetic components is analyzed by finite element simulation software and compared with the existing integration method; this decoupling integration method can make the flux distribution more uniform and improve the core utilization. The results show that the volume and weight are reduced by 31.2 % and 25.3 % compared with those of the separated magnetic parts, and the efficiency is also consistent with that of the separated magnetic parts, which verifies the correctness and feasibility of the theoretical analysis.

Aticaprant, a kappa opioid receptor antagonist, and the recovered 'interest and pleasure' in the concept of major depressive disorder.

Lack of positive mood and anhedonia probably are the most specific depressive symptoms. Anhedonia is a multifaceted concept: the clinical language describes anticipatory/consummatory anhedonia and sensory/social anhedonia while the cognitive neuroscience language describes readiness for reward, energy expenditure to attain reward, updating reward presence and value. Mounting evidence supports the potential of kappa-opioid receptor (KOR) antagonists as novel pharmacotherapies for major depressive disorder : aticaprant is a potent, selective, short-acting KOR antagonist. The fast-fail approach evaluated the impact of aticaprant on the brain circuitry hypothesized to mediate anhedonia and significantly increased fMRI activation in the ventral striatal activation during reward anticipation as compared to placebo; the aticaprant induced changes in the self-reported psychological measures of anhedonia were rather inconsistent. The recently reported results of a phase 2a randomized, double-blind, placebo-controlled trial investigating the efficacy and safety of aticaprant, co-administered to an oral SSRI/SNRI antidepressant in depressed patients who had an inadequate response to 1 or 2 antidepressants. The improvement from baseline favoured the co-administration of aticaprant over the co-administration of placebo at all time points (during 6 weeks), and this was confirmed by higher response rates with aticaprant. A mid-split of patients with higher or lower than median anhedonia also showed that the patients with higher baseline anhedonia had the largest decrease on the MADRS. Tolerability and safety were reassuring. These promising results of the co-administration of aticaprant to an SSRI/SNRI in depressed patients with prominent anhedonia support he further investigation of aticaprant in larger trials.

Novel ZIFs nanostructures electro-engineered at carbon fiber for the highly sensitive and selective detection of isoeugenol.

Novel zeolitic imidazolate frameworks (ZIFs), classical subtypes of metal organic frameworks (MOFs), and nanostructures are electro-engineered onto carbon fiber (CF), leading to a unique freestanding electrochemical platform of budlike nano Zn-ZIFs decorated CF (BN-Zn-ZIFs/CF). The unique morphology, structure, and composition are characterized by electron microscopy and energy spectrum analysis. Notably, the BN-Zn-ZIFs/CF platform displays superb electrocatalysis towards the oxidation of isoeugenol with encouragingly low overpotential and high current response. The strong electrocatalytic oxidation capability of BN-Zn-ZIFs/CF makes it an excellent sensing platform for isoeugenol detection. BN-Zn-ZIFs/CF sensor exhibits high-performance isoeugenol sensing with an extremely low limit of detection (13nM) and wide detection range (0.1-700µM). Besides, the BN-Zn-ZIFs/CF sensor can greatly resist interference from common ions, major biomolecules, and some amino acids. Moreover, excellent reliability, stability, and practicality are obtained. Our work demonstrates that the as-prepared BN-Zn-ZIFs/CF can act as an high-performance electrochemical sensor for the isoeugenol detection, the well-developed ZIF nanocrystal-modified conductive substrates can be a unique platform for the efficient sensing of other molecules, and the electrochemical engineering strategy can be an effective method for the growing of fresh MOF nanocrystals at conductive substrates in various electrochemical applications.

Structural, optical, and gas sensing characteristics of synthesized environmentally friendly ZnO-ZnAl2O4 nanocomposites

In this study, we synthesized ZnO-ZnAl2O4 composites from orange peel extract by using an environmentally friendly approach. ZnO-ZnAl2O4 composites with different Al content, namely 30, 40, 50, 60, and 70 at%, were successfully synthesized, and they were characterized in detail using advanced techniques to study their structures, phases, morphologies, and electrical and optical properties. Gas sensing measurements for H2S gas showed that the sensor with 70 at% Al had the best response at 350 °C along with long-term stability. We attribute this high response to the high specific surface area (48.8 m2·g−1), the formation of ZnO-ZnO homojunctions and ZnO-ZnAl2O4 heterojunctions, and the high intrinsic sensing properties of the ZnO phase. This study is expected to contribute to the development of green approaches for the synthesis of environmentally friendly gas sensing materials.

Sea urchin inspired ultrafast response low humidity sensor based on ionic liquid modified UiO-66 with advanced applications

Numerous applications require low humidity sensors that not only sensitive but also stable, small hysteresis, high resolution and fast response. However, most reported low humidity sensors cannot possess these properties at the same time. In this work, inspired by sea urchin, we developed an ionic liquid (IL) modified metal organic framework (UiO-66) based low humidity sensor. Owing to the synergistic effect of the hydrophilicity and ionic conductivity of IL and the steric hindrance effects of UiO-66, the optimized low humidity sensor simultaneously exhibits high response (47.5), small hysteresis (0.3 % RH), ultrafast response speed (0.2 s), high resolution (1 % RH), and excellent long-term stability (>120 days). In particular, the sensor has been proved to have potential applications in visual humidity detection and water source location. This work provides a preliminary design principle that will contribute to the preparation of high-performance low humidity sensing materials.

Short-term results with faricimab in neovascular age-related macular degeneration resistant to both ranibizumab and aflibercept

PurposeSome patients with neovascular age-related macular degeneration (nAMD) do not respond to anti-VEGF treatment or develop tolerance or tachyphylaxis. If optimal treatment response is lacking with a given drug, switching to another is a common practice. The aim of this study was to report short-term outcomes of treatment switch to faricimab in real-world patients with nAMD resistant to both aflibercept and ranibizumab. DesignSingle-center, retrospective real-world cohort study. MethodsChart-review of 13 eyes of 13 multi-switch patients using electronic injection database, electronic medical records, and optical coherence tomography (OCT) data from May–September 2023. ResultsFaricimab treatment led to absence of fluid (subretinal, or both subretinal and intraretinal fluid) in 31% of the eyes and a reduction of fluid in 77% of the eyes at 4 weeks following the switch. The best-corrected visual acuity did not change significantly. No ocular or systemic safety events were observed. ConclusionsSwitching to faricimab seems a reasonable option in patients with nAMD who were previously resistant to both aflibercept and ranibizumab treatment. We noted a high rate of morphological response and improvement in anatomical parameters, with nearly one-third of the patients achieving dry macula after just one injection. No change in BCVA was seen. No safety issues were noted. The durability of these results warrants additional investigations. Trial registrationClinicalTrials.gov, registration number: NCT06231121, date of registration: 21/01/2024, retrospectively registered.

The Impact of Incentives on Data Collection for Online Surveys: Social Media Recruitment Study.

The use of targeted advertisements on social media platforms (eg, Facebook and Instagram) has become increasingly popular for recruiting participants for online survey research. Many of these surveys offer monetary incentives for survey completion in the form of gift cards; however, little is known about whether the incentive amount impacts the cost, speed, and quality of data collection. This experiment addresses this gap in the literature by examining how different incentives in paid advertising campaigns on Instagram for completing a 10-minute online survey influence the response rate, recruitment advertising cost, data quality, and length of data collection. This experiment tested three incentive conditions using three Instagram campaigns that were each allocated a US $1400 budget to spend over a maximum of 4 days; ads targeted users aged 15-24 years in three nonadjacent designated market areas of similar size to avoid overlapping audiences. Four ad creatives were designed for each campaign; all ads featured the same images and text, but the incentive amount varied: no incentive, US $5 gift card, and US $15 gift card. All ads had a clickable link that directed users to an eligibility screener and a 10-minute online survey, if eligible. Each campaign ran for either the full allotted time (4 days) or until there were 150 total survey completes, prior to data quality checks for fraud. The US $15 incentive condition resulted in the quickest and cheapest data collection, requiring 17 hours and ad spending of US $338.64 to achieve 142 survey completes. The US $5 condition took more than twice as long (39 hours) and cost US $864.33 in ad spending to achieve 148 survey completes. The no-incentive condition ran for 60 hours, spending nearly the full budget (US $1398.23), and achieved only 24 survey completes. The US $15 and US $5 incentive conditions had similar levels of fraudulent respondents, whereas the no-incentive condition had no fraudulent respondents. The completion rate for the US $15 and US $5 incentive conditions were 93.4% (155/166) and 89.8% (149/166), respectively, while the completion rate for the no-incentive condition was 43.6% (24/55). Overall, we found that a higher incentive resulted in quicker data collection, less money spent on ads, and higher response rates, despite some fraudulent cases that had to be dropped from the sample. However, when considering the total incentive amounts in addition to the ad spending, a US $5 incentive appeared to be the most cost-effective data collection option. Other costs associated with running a campaign for a longer period should also be considered. A longer experiment is warranted to determine whether fraud varies over time across conditions.

Self-centering dual rocking core system with viscous dampers in additional rocking sections

To mitigate the high mode effects and reduce the force requirements of the structural members in the multi-story self-centering dual rocking core (SDRC) system, this paper proposes the multiple self-centering dual rocking core system with viscous dampers in additional rocking sections (MSDRCV system). The sketch and ideal working mechanisms of the MSDRCV system are interpreted. The additional rocking sections are set to decrease the force requirements of structural members and viscous dampers are included to mitigate high mode responses of the additional rocking sections, introducing seismic performance enhancement. Comparative analyses on a 9-story MSDRCV system with viscous dampers in rocking sections, a 9-story multiple self-centering dual rocking core system without viscous dampers in rocking sections (MSDRC system) and a 9-story SDRC system were carried out. The MSDRCV and MSDRC system can realize the reduction of the force demands in structural members in contrast to the SDRC system. Nevertheless, the high mode responses caused the uncontrollable displacement concentration in the MSDRC system and hence aggravated the seismic performance under rare seismic events. The analysis results in the frequency domain confirmed that the viscous dampers in the MSDRCV system can efficiently control the high-mode responses. The effects of the design parameters of the viscous dampers on the peak responses of the MSDRCV systems were comprehensively studied via parametric analyses. The results offer guidance for the viscous dampers design.

FINAL outcome ANALYSIS FROM THE PHASE II TUXEDO-1 TRIAL OF TRASTUZUMAB-DERUXTECAN IN HER2-positive breast cancer PATIENTS WITH active brain metastases.

Brain metastases (BM) are a devastating complication of HER2-positive metastatic breast cancer (BC) and treatment strategies providing optimized local and systemic disease control are urgently required. The antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) improved progression-free survival (PFS) and overall survival (OS) over trastuzumab emtansine but data regarding intracranial activity is limited. In the primary outcome analysis of TUXEDO-1, a high intracranial response rate (RR) was reported with T-DXd. Here, we report final PFS and OS results. TUXEDO-1 accrued adult patients with HER2-positive BC and active BM (newly diagnosed or progressing) without indication for immediate local therapy. The primary endpoint was intracranial RR; secondary endpoints included PFS, OS, safety, quality-of-life (QoL), and neurocognitive function. PFS and OS were estimated with the Kaplan-Meier method and analysed in the per-protocol population. At 26.5 months median follow-up, median PFS was 21 months (95% CI 13.3-n.r.) and median OS was not reached (95% CI 22.2-n.r.). With longer follow-up, no new safety signals were observed. The most common grade 3 adverse event was fatigue (20%). Grade 2 interstitial lung disease and a grade 3 symptomatic drop of left-ventricular ejection fraction were observed in one patient each. QoL was maintained over the treatment period. T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive BC BM in line with results from the pivotal trials. These results support the concept of ADCs as systemic therapy for active BM.

MWIRGas-YOLO: Gas Leakage Detection Based on Mid-Wave Infrared Imaging.

The integration of visual algorithms with infrared imaging technology has become an effective tool for industrial gas leak detection. However, existing research has mostly focused on simple scenarios where a gas plume is clearly visible, with limited studies on detecting gas in complex scenes where target contours are blurred and contrast is low. This paper uses a cooled mid-wave infrared (MWIR) system to provide high sensitivity and fast response imaging and proposes the MWIRGas-YOLO network for detecting gas leaks in mid-wave infrared imaging. This network effectively detects low-contrast gas leakage and segments the gas plume within the scene. In MWIRGas-YOLO, it utilizes the global attention mechanism (GAM) to fully focus on gas plume targets during feature fusion, adds a small target detection layer to enhance information on small-sized targets, and employs transfer learning of similar features from visible light smoke to provide the model with prior knowledge of infrared gas features. Using a cooled mid-wave infrared imager to collect gas leak images, the experimental results show that the proposed algorithm significantly improves the performance over the original model. The segment mean average precision reached 96.1% (mAP50) and 47.6% (mAP50:95), respectively, outperforming the other mainstream algorithms. This can provide an effective reference for research on infrared imaging for gas leak detection.

Coupled magneto-mechanical response of laminate composites comprising a layer of Ni-Mn-Ga microparticles

Ni-Mn-Ga ferromagnetic shape memory alloys (FSMAs), exhibiting a giant magnetic field induced strain (MFIS), high work output and fast response, are highly promising materials for emerging technologies to be used in automotive, aerospace, and robotics industries, among others. Their magnetic-to-mechanical energy conversion ability is characterized by the coupled magneto-mechanical response they show when magnetic field and mechanical stress are simultaneously applied. In the present work we elaborated a series of laminated composites comprising a layered ensemble of single crystalline Ni-Mn-Ga microparticles built-in between Cu foils via small layers of silicone rubber. Such a simple and robust design enabled an in-depth study of the simultaneous influence of the magnetic field and compressive opposing stress on MFIS and the generated force of the particle layer driving out-of-plane magnetomechanical response of the laminate. Self-consistent parameters characterizing a magnetic field- and stress-induced martensitic variant reorientation in the particles were disclosed by the measurements and comprehensive analysis of both the magnetization curves under opposing constant stresses (complemented by tracking residual strains with X-ray µ-CT imaging) and compressive stress-strain dependences under transversal magnetic field. In particular, an accurate value of the magnetic-to-mechanical energy conversion coefficient, equal to Cme = (2.3 ± 0.13) MPa/T2, and the value of maximum magnetostress of about 2.3 MPa generated by microparticles were determined, in a good agreement with bulk Ni-Mn-Ga single crystals (SC). In contrast to bulk SC, particles are technologically and costly more efficient. They have much higher degree of freedom in terms of composites design allowing the development of advanced miniature actuators and sensors.

Comprehensive analysis and identification of subtypes and hub genes of high immune response in lung adenocarcinoma

BackgroundThe advent of immunotherapy targeting immune checkpoints has conferred significant clinical advantages to patients with lung adenocarcinoma (LUAD); However, only a limited subset of patients exhibit responsiveness to this treatment. Consequently, there is an imperative need to stratify LUAD patients based on their response to immunotherapy and enhance the therapeutic efficacy of these treatments.MethodsThe differentially co-expressed genes associated with CD8 + T cells were identified through weighted gene co-expression network analysis (WGCNA) and the Search Tool for the Retrieval of Interacting Genes (STRING) database. These gene signatures facilitated consensus clustering for TCGA-LUAD and GEO cohorts, categorizing them into distinct immune subtypes (C1, C2, C3, and C4). The Tumor Immune Dysfunction and Exclusion (TIDE) model and Immunophenoscore (IPS) analysis were employed to assess the immunotherapy response of these subtypes. Additionally, the impact of inhibitors targeting five hub genes on the interaction between CD8 + T cells and LUAD cells was evaluated using CCK8 and EDU assays. To ascertain the effects of these inhibitors on immune checkpoint genes and the cytotoxicity mediated by CD8 + T cells, flow cytometry, qPCR, and ELISA methods were utilized.ResultsAmong the identified immune subtypes, subtypes C1 and C3 were characterized by an abundance of immune components and enhanced immunogenicity. Notably, both C1 and C3 exhibited higher T cell dysfunction scores and elevated expression of immune checkpoint genes. Multi-cohort analysis of Lung Adenocarcinoma (LUAD) suggested that these subtypes might elicit superior responses to immunotherapy and chemotherapy. In vitro experiments involved co-culturing LUAD cells with CD8 + T cells and implementing the inhibition of five pivotal genes to assess their function. The inhibition of these genes mitigated the immunosuppression on CD8 + T cells, reduced the levels of PD1 and PD-L1, and promoted the secretion of IFN-γ and IL-2.ConclusionsCollectively, this study delineated LUAD into four distinct subtypes and identified five hub genes correlated with CD8 + T cell activity. It lays the groundwork for refining personalized therapy and immunotherapy strategies for patients with LUAD.

P-669 Not the oocyte yield but the number of embryos predicts live birth at high response: analysis of 39,136 fresh IVF/ ICSI cycles from National Database

Abstract Study question Oocyte or embryo yield- which is a better predictor of live birth (LB) in fresh cycle IVF/ ICSI? Summary answer The embryo yield is better than oocyte in predicting fresh-cycle LB and positively correlates with LB at high ovarian response when the oocytes yield doesn’t. What is known already As the LB rates plateau after a certain oocyte yield, the number of oocytes collected no longer can predict the live birth in IVF/ ICSI cycles with fresh embryo transfer.Since pregnancy outcomes also depend on the number of mature oocytes obtained, fertilisation rate and subsequent embryo development, it can be postulated that the number of total or transferrable embryos could be a better predictor of LB. Study design, size, duration Retrospective analysis of 39,136 fresh IVF/ ICSI cycles that met the inclusion criteria from the national database published by Human Fertilisation and Embryology Authority (HFEA) in the United Kingdom. We analysed 2 years of published data between January 2015 and December 2016. Participants/materials, setting, methods Only the first cycles of IVF/ ISCI that had oocyte retrieval procedure with intended fresh embryo transfer were included. Couples with any cause of infertility and female partners aged up to 44 years were included. Very few cycles with &amp;gt;25 oocytes had fresh transfer, therefore excluded. The ovarian response has been graded by 0-5, 6-10, 11-15, 16-20, 21-25 collected oocytes. Significant confounders found in univariate analysis were adjusted for in the multiple regression model. Main results and the role of chance Women’s age, method of insemination (IVF or ICSI) and number of transferred embryos and stage of transfer significantly associated with LB in univariate analysis (p &amp;lt; 0.0001 each). The oocyte yield predicted fresh-cycle LB only in low response group (0-5 oocytes), but not in higher response groups. Total number of embryos, the number of transferable embryos and embryo utilisation rate remained positively correlated with LB in all response groups. The number of transferable embryos found to be the best predictor of LB with the highest adjusted OR 1.51 (CI:1.4-1.65, p &amp;lt; 0.0001) in the lowest response (0-5 oocyte) group, that gradually declined to 1.06 (CI:1.03-1.10, p = 0.0003) in 21-25 oocytes group. Followed next by the total number of embryos with the highest adjusted OR of 1.20 (CI:1.13-1.27, p &amp;lt; 0.0001) in the lowest response (0-5 oocytes) group, down to 1.04 (CI:1.02-1.06, p = 0.0003) in the 21-25 oocytes group. The number of oocytes was the weakest in predicting LB (adjusted OR 1.07 (CI 1.02-1.12; p = 0.003) in the 0-5 oocytes group only. The inference remained the same when ICSI cycles with supposedly sperm factor was excluded. Limitations, reasons for caution Information on patient’s BMI or stimulation dose is not available in the HFEA database. However, it might have little impact in our findings, given large sample size. Ages are given in groups, so the groups taken as ordinal (dummy) variables in multiple regression analysis. Cumulative LB data were not available. Wider implications of the findings Having been influenced by both oocyte and sperm competency, the number of transferable embryos may have a stronger relation with the pregnancy outcomes than merely the oocyte number. On theory, this may be applicable for cumulative LB too, but awaiting confirmation by data evidence. Trial registration number Not applicable

P-577 A randomized trial to compare the live birth rate following the progestin-primed ovarian stimulation versus the antagonist protocol in women with anticipated high ovarian responses

Abstract Study question Is there difference in the live birth rate following the progestin-primed ovarian stimulation (PPOS) versus the antagonist protocol in women with anticipated high ovarian responses? Summary answer The live birth rates of the first frozen embryo transfer following PPOS and the antagonist protocol were comparable in women with anticipated high ovarian responses. What is known already Progestin when given orally inhibits the pituitary LH surge during ovarian stimulation when taken orally i.e. progestin-primed ovarian stimulation. Two randomized trials showed similar number of oocytes for PPOS and the antagonist protocol in oocyte donation cycles. However, there is still no randomized trial to compare the live birth rate between PPOS and the antagonist protocol. Study design, size, duration This is a randomized controlled trial of 784 infertile women conducted from June 2020 and October 2021. Participants/materials, setting, methods Infertile women aged &amp;lt;43 years undergoing the first IVF cycle in a tertiary fertility center and having antral follicle count &amp;gt;15 randomly assigned in a 1:1 ratio into two groups: PPOS group and the antagonist group. Medroxyprogesterone 10 mg daily was given from the start of ovarian stimulation until the day of ovulation trigger in the PPOS group. The primary outcome was the live birth rate of the first frozen embryo transfer. Main results and the role of chance 784 women were randomly assigned into two groups: PPOS group (n = 392) and antagonist group (n = 392). Embryo transfer was either cancelled or postponed in 62 (62/392, 15.8%) women in the PPOS group and 65 (65/392, 16.6%) in the antagonist group because of no transferable embryos or no frozen embryo transfer within 6 months following randomization. The two groups were similar in demographic characteristics and number of oocytes obtained/fertilized, the number of cleaving embryos, number of good quality embryos at day 3, number of blastocysts developed and number of embryo/blastocyst frozen. There was no statistically significant difference in the live birth rate of the first frozen embryo transfer cycle between the progestin-primed ovarian stimulation and antagonist groups based on both intention to treat [37.5.0% (147/392) versus 32.7% (128/392), RR 1.148 (95% CI = 0.949–1.390), P = 0.16] and per protocol analysis [44.5% (147/330) versus 39.1.% (128/327), RR 1.138 (95%CI = 0.950–1.364), P = 0.16]. Both groups showed comparable clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy and cumulative live birth rates. Limitations, reasons for caution Women with anticipated high ovarian responses were recruited and the results may not be extrapolated to the general population seeking IVF. This is not a blind study although the live birth rate as the primary outcome is objection. The duration of the study is 6 months since randomization. Wider implications of the findings In situations in which fresh embryo transfer is not required such as oocyte/embryo freezing for fertility preservation, oocyte donation or preimplantation genetic testing, the PPOS protocol may be preferred over the antagonist protocol. Trial registration number NCT04414761

Directly Acting Anti-Viral Drugs and Its Metabolic Side Effects in Patients with Chronic HCV

Abstract Background Hepatitis C virus (HCV) is a major cause of chronic liver disease, with an estimated 170 million people infected worldwide. Treatment of hepatitis C virus has traditionally been difficult because of low rates of treatment success and high rates of treatment discontinuation due to side effects. Aim of the Work The aim of this work is to study side effects of directly acting anti HCV drug (DAA) and its progression in metabolism of lipid profile, blood sugar level, and renal function. Patients and Methods This case study had been carried out on 200 subjects presented to Department of Internal Medicine at Kobbri ELkobba hospital inpatient and outpatient clinics between March 2016 and September 2016. Results sustained virological response (12 weeks) after end of the treatment in more than 90% of patients, Liver function parameters including albumin, bilirubin, and prothrombin time and liver enzymes Ast, Alt improved in the majority of patients during and after the end of therapy,but there is significant increase in urea level, serum creatinin and HbA1C. There is significant decrease in LDL and mild increase in TG level. Conclusion Once-daily oral daclatasvir plus sofosbuvir with or without Ribavirin was associated with high rates of sustained virologic response among patients infected with HCV, including chronic cirrhotic patients and relapsers, successful treatment associated with Improvement of liver function parameters in the majority of patients, Increase in urea level, serum creatinin and HbA1C. There is significant decrease in LDL and mild increase in TG level.

Impact of Direct Acting Antivirals Therapy on Novel Fibrosis Index for Assessment of Hepatic Fibrosis in Comparison with AST to Platelet Ratio and Fibrosis-4 (FIB-4) Indices in Egyptian Patients with Chronic Hepatitis C Infection in Correlation with Fibroscan

Abstract Background Chronic viral infection causes multiple waves of inflammation and tissue repair which involves deposition of extracellular matrix resulting in scarring or progressive fibrosis over time and ultimately leading to liver cirrhosis. The introduction of DAAs has improved eradication rate of HCV and achievement of SVR. In addition to the high rates of sustained virological response (SVR), hepatic fibrosis may regress, and the risks of complications, such as hepatic failure and portal hypertension are reduced after SVRs, Stage of liver fibrosis in chronic HCV infection is a well-established factor that determines the severity of disease and associated complications. Numerous noninvasive fibrosis scores, imaging techniques and new serum fibrosis markers have been applied to evaluate the phases of liver fibrosis, and have mostly replaced liver biopsy Transient elastography (TE) is the most accurate method with high sensitivity and specificity for advanced fibrosis the aminotransferase (AST)/platelet ratio index (APRI) and the fibrosis-4 (FIB-4) scores are the most widely used in viral hepatitis C patients, particularly in those with significant fibrosis and cirrhosis. Objective The aim of this study is to evaluate Impact of Direct Acting Antivirals therapy on Novel fibrosis index for assessment of hepatic fibrosis in comparison with AST to Platelet ratio and fibrosis-4(FIB-4) indices in Egyptian patients with chronic hepatitis C infection in correlation with fibro scan. Patients and Methods This is a prospective Cohort clinical study performed on 100 Egyptian patients are ≥18 years of age who have chronic infection with hepatitis C who will be treated with combination of IFN-free DAAs (Sofosbuvir &amp; Daclatasvir ± Ribavirin) for 3 months. oral informed consent was taken from all patients included in the study. Results In the current study, there was significant regression of degree of fibrosis after treatment with DAAs in all patients achieving SVR by fibroscan, APR and fib4. novel fibrosis index is reliable and good tool in assessment of liver fibrosis in correlation to fibroscan, APRI and FIB4 especially significant fibrosis with the cut off value in prediction of hepatic fibrosis stage 4 was &amp;gt;3.1 and has sensitivity of 81.5% while the specificity was 74.1%. The positive predictive value was 66% while the negative predictive value was 86.8% Conclusion Novel fibrosis index has been found to be good reliable marker for assessment of liver fibrosis with high accuracy of predicting f4 fibrosis stage. There was significant marked reduction of fibrosis degree by fibroscan and non invasive indices (APRI &amp;FIB4) after treatment with directly acting antiviral in both cirrhotic and non cirrhotic patients regardless the treatment regimen used with improved overall liver function tests especially albumin level, liver enzymes, hemoglobin level and platelet count in patients who reached SVR.

P-608 Cumulative live birth rates after 3 consecutive embryo transfers in freeze-all cycles following gonadotropin-releasing hormone antagonist protocol versus progesterone-primed ovarian stimulation

Abstract Study question Do cumulative live birth rates in freeze-all cycles differ between gonadotropin-releasing hormone (GnRH) antagonist protocol and progesterone-primed ovarian stimulation (PPOS)? Summary answer GnRH antagonist and PPOS protocols have similar cumulative live birth rates in freeze-all cycles. What is known already GnRH antagonists and progesterone have been used for pituitary suppression in ovarian stimulation cycles. While PPOS protocol has the advantage of oral usage and lower cost, data regarding the laboratory and clinical outcome is limited and confounding. Freeze-all cycles might provide a better model to assess the impact of PPOS protocol and GnRH antagonist protocol on laboratory, clinical outcomes and cumulative live birth rates. Study design, size, duration A retrospective cohort study on IVF cycles performed (n = 568) between January 2020 and May 2022.The entire cohort of embryos were cryopreserved at the blastocyst stage.Inclusion criteria were 18-42 years of age,ICSI for severe male factor infertility.Exclusion criteria were PGD and severe endometriosis.Indications for cryopreservation in the antagonist group were high ovarian response (n:102),endometrial polyps (n:34),high follicular phase P4(n:48) and elective purposes(n:260).PPOS was used due to a transient shortage of GnRH antagonist in the market (n:124). Participants/materials, setting, methods 568 women (GnRH antagonist:444; PPOS:124) were included in the analysis.The primary outcome was the cumulative live birth rate (CLBR) after 3 consecutive embryo transfer cycle, and the secondary outcome parameters were the number of M-II oocytes, fertilization rate and blastocyst utilization rate. Student’s t-test was used for normally distributed continuous data and Fisher’s exact tests for categorical data were used. A generalized estimating equation model and logistic regression analysis were performed to adjust for confounding factors. Main results and the role of chance The mean age of the GnRH antagonist group was 34.1 ± 5.3 and 34.5 ± 5.7 years in PPOS group (p = 0.38). The baseline characteristics including BMI, serum AMH levels, duration of infertility, duration of stimulation and gonadotropin ampules used were similar in both groups. Estradiol and progesterone levels at the time of ovulation trigger were higher in GnRH antagonist cycles (2383.5 ± 1375.4 vs 2034.5 ± 1218.3, p = 0.02 and 0.7 ± 0.6 vs 0.5 ± 0.4, p = 0.01, respectively) The mean number of cumulus-oophorus complexes (12.9 ± 7.4 vs 11.5± 10.0, p = 0.61), M-II oocytes (10.0± 6.1 vs 9.1± 6.1, p = 0.14), frozen blastocysts (4.8± 3.5 vs 4.7± 3.6, p = 0.71) were similar between GnRH antagonist and PPOS groups, respectively. Fertilization rates (84.4% vs 87.2%, p = 0.12) and blastocyst utilization rates (63.4% vs 65.9%, p = 0.34) were also similar between GnRH antagonist and PPOS groups, respectively. The number of transferred embryos and the number of unused blastocysts were similar between groups. The CLBRs after one IVF cycle and 3 consecutive frozen-thawed blastocyst transfers were comparable in GnRH antagonist and PPOS cycles (56.8% and 53.2%, p = 0.37, respectively). Limitations, reasons for caution This was a retrospective study with relatively small sample size performed at a single fertility center, which may limit the generalizability of our findings. Wider implications of the findings If the fresh embryo transfer is not intended, PPOS protocol can be used in all patient types with cost-effective and patient-friendly manner. Trial registration number 2024.013.IRB2.012