Start Of Cycle Research Articles

Structural development on Ru and RuO2 electrodes during oxygen evolution – a soft X-ray absorption spectroscopy approach

Time resolved in-situ X-ray absorption spectroscopy (XAS) in soft X-ray region was used to characterize polarized interphase on Ru and Ru oxide based electrodes under oxygen evolution reaction (OER) conditions. XAS spectra were used to align the type and population of oxygen-containing species formed at electrodes at anodic potentials with local electronic structure of the OER catalyst. The soft XAS data do not identify a single rate limiting process for OER at potentials negative to 1.7 V vs. RHE. Individual intermediates of the oxygen evolution process coexist at the surface at potentials preceding the actual OER onset. The OER is accompanied with redistribution of the electron density resulting for a start of the catalytic cycle reflecting the transfer of the electrons from water to the external circuit during catalyzed water oxidation. The observed spectral behavior indicates a confinement of the OER to the coordination unsaturated sites (cus) at the surface.

Treatment of cardiotoxicity in patients with invasive breast cancer during neoadjuvant chemotherapy

Aim – assessment of the effectiveness of complex therapy to reduce the development of early cardiovascular complications. Materials and methods. Information from medical histories and outpatient follow-up cards of 139 patients with invasive breast cancer was analyzed: in the G.V. Bondar Republican Cancer Center 64 patients (main and control groups); as an additional comparison group, the study included 75 patients of the Samara Regional Clinical Oncology Dispensary. Patients in the control group (33 people) and the Samara Regional Clinical Oncology Dispensary group (75 people) received standard therapy (RUSSCO, recommendations, 2023): doxorubicin 60 mg/m2 IV on day 1 + cyclophosphamide 600 mg/m2 IV on day 1 Day 4 – 4 courses. In 31 patients of the main observation group, in addition to similar drug treatment, in order to prevent the development of early cardiovascular complications, the method was used, which included 7 courses before the start of 1 cycle of chemotherapy + 3 courses of interval normobaric hypoxic therapy (INHT) before the start of each subsequent cycle of chemotherapy. Results. When analyzing the total effectiveness of treatment between the groups of patients, statistically significant differences were obtained: the control and main groups were compared (χ2=5.4, p=0.03), the group of the Samara Regional Clinical Oncology Dispensary group and the main group (χ2=3.45, p=0.076). Conclusions. Hypoxic therapy significantly affects the quality of life of patients. For all indicators reflecting quality of life, traditional treatment was inferior to combination drug therapy with INHT.

Evaluation of Drug-Drug Interaction Potential of Talquetamab, a T-Cell-Redirecting GPRC5D×CD3 Bispecific Antibody, as a Result of Cytokine Release Syndrome in Patients with Relapsed/Refractory Multiple Myeloma in MonumenTAL-1, Using a Physiologically Based Pharmacokinetic Model.

Cytokine release syndrome, commonly associated with T-cell immunotherapies, was observed with talquetamab, a T-cell-redirecting bispecific antibody, in the phase I/II MonumenTAL-1 study, leading to elevated interleukin (IL)-6, which can suppress cytochrome P450 (CYP) enzyme activity. We aimed to evaluate the potential impact of elevated IL-6 on the exposure of co-administered CYP450 substrates for two scenarios: (1) the observed median IL-6 profile and (2) a profile with the highest IL-6 maximum concentration following talquetamab treatment. A physiologically based pharmacokinetic model was developed based on the literature and simulations performed using observed IL-6 profiles from patients in MonumenTAL-1 who received the subcutaneous recommended phase 2 doses (RP2Ds) of talquetamab: 0.4 mg/kg weekly (QW) and 0.8 mg/kg every other week (Q2W). Median IL-6 maximum concentration was 18.4 and 7.1 pg/mL, and maximum IL-6 maximum concentration was 213 and 3503 pg/mL for talquetamab QW and Q2W RP2Ds, respectively. For the median IL-6 profile, no interaction between IL-6 and studied CYP substrates was predicted at either RP2D. The maximum IL-6 profile predicted weak-to-moderate impact on exposure of CYP2C19, CYP3A4, and CYP3A5 substrates and minimal impact on exposure of CYP1A2 substrates at both RP2Ds. Impact on exposure of CYP2C9 substrates was predicted as minimal at QW and minimal-to-weak at Q2W RP2Ds. Time to return to 20% difference from baseline enzymatic activity was predicted as 7 and 9 days after start of cycle 1 for QW and Q2W RP2Ds, respectively. These modeling results suggest that IL-6 release due to talquetamab-induced cytokine release syndrome has limited impact on potential drug-drug interactions, with the highest likelihood of impact occurring from initiation of talquetamab step-up dosing up to 7 (QW) or 9 (Q2W) days after first treatment dose in cycle 1 and during and after cytokine release syndrome. Multiple myeloma can be treated with immunotherapies such as the bispecific antibody, talquetamab, which binds the novel antigen G protein-coupled receptor family C group 5 member D on multiple myeloma cells and CD3 on T cells and induces T-cell-mediated lysis of multiple myeloma cells. Following talquetamab treatment, many patients experience cytokine release syndrome, an inflammatory immune response where levels of proinflammatory cytokines, including interleukin (IL)-6, are increased. Interleukin-6 can suppress the activity of important enzymes in the body (cytochrome [CYP] P450s) that are involved in drug clearance. This study used a physiologically based pharmacokinetic computer model to investigate the potential impact of increased IL-6 levels on CYP450 enzymes to determine subsequent impact on drugs that are metabolized by CYP450 enzymes. The results showed no predicted interaction between median levels of IL-6 observed in patients and CYP substrates (such as caffeine and omeprazole) with talquetamab. In a simulation that assessed higher (maximum) IL-6 levels observed in patients, the predicted impact of IL-6 was minimal to weak for most of the CYP substrates assessed. The effect on CYP450 enzymatic activity was highest from initiation of talquetamab step-up dosing up to 7-9 days after the first treatment dose of talquetamab. These results suggest that, in this treatment time period, elevated IL-6 levels due to talquetamab-induced cytokine release syndrome have limited impact on drugs that are CYP substrates that may be used in conjunction with talquetamab, but that the concentration and toxicity of these drugs should be monitored and the dose of CYP substrate adjusted as required.

A Pharmacologic Evaluation of Buprenorphine in Pregnancy and the Postpartum Period.

The dosing regimen in the package insert for sublingual buprenorphine is similar for pregnant and nonpregnant people despite the physiologic changes seen during pregnancy. To compare plasma buprenorphine pharmacokinetics during and after pregnancy and relate buprenorphine concentration to the pharmacodynamic endpoints of pupil diameter, Clinical Opioid Withdrawal Scale (COWS), and craving scores. Prospective cohort of 22 pregnant people undergoing 33 pharmacologic studies (6-8 hours each) during pregnancy or postpartum. Participants were on a stable daily dose of 2-8 mg sublingual buprenorphine every 6 or 8 hours. The dosing frequency was selected by the participant. On study day, baseline measurements of plasma buprenorphine, pupil diameter, COWS, and craving scores were obtained, then the usual morning dose was taken, and measurements were repeated several times over 1 dosing interval. The dose-normalized area under the plasma buprenorphine concentration time curve was significantly (P = 0.036) lower during pregnancy (155 ± 52 ng × min/mL) than postpartum (218 ± 113 ng × min/mL). Buprenorphine trough concentrations were similar at the start (1.1 ± 0.7 ng/mL) and end of a dosing cycle (1.2 ± 0.8 ng/mL) regardless of dosing frequency. Pupillary diameter, COWS, and craving scores returned to baseline as buprenorphine concentrations approached ~1 ng/mL. Pregnant people require a higher dose of buprenorphine to achieve concentrations comparable to nonpregnant people. There is a temporal relationship between the plasma buprenorphine concentration and the pharmacodynamic markers of pupillary diameter, COWS, and craving scores. An average plasma concentration of ~1 ng/mL was associated with the lowest level of COWS and craving scores.

Sodium orthovanadate protects against ulcerative colitis and associated liver damage in mice: insights into modulations of Nrf2/Keap1 and NF-κB pathways.

Ulcerative colitis (UC) is a prominent category of disease that is associated with bowel inflammation, it can occur at any period of life and is prevalently rising on a global scale. Dextran sulfate sodium (DSS) has been extensively used to develop colitis due to its ability to mimic human UC, providing consistent and reproducible inflammation, ulceration, and disruption of the epithelial barrier in the colon. Chronic inflammation in the gut can lead to alterations in the gut-liver axis, potentially impacting liver function over time, while direct evidence linking diversion colitis to liver damage is limited. Thus, the present study aims to assess the gut and liver damage against DSS and the possible molecular mechanisms. Forty-seven animals were randomly assigned to six groups. Ulcerative colitis was induced using 2.5% w/v DSS in three alternate cycles, each lasting 7 days, with 1-week remission periods in between. SOV (5 and 10 mg/kg, orally) and the standard drug 5-aminosalicylic acid (100 mg/kg, orally) were administered from the start of the 2nd DSS cycle until the end of the experiment. Biochemical parameters, ELISA, histopathological, and immunohistochemical analyses have been conducted to assess damage in the colon and liver. SOV significantly reduced colitis severity by lowering the DAI score, oxidative stress markers (LPS, IL-1β, MPO, nitrite), and restoring liver biomarkers (SGPT, SGOT). Histopathological findings supported these protective benefits in the liver and gut. Moreover, immunohistochemical analysis showed SOV enhanced the expression of the cytoprotective mediator Nrf2/Keap-1 and reduced the expression of inflammatory mediators NF-κB and IL-6. Present findings concluded that SOV demonstrated a dose-dependent effect against UC through anti-inflammatory and antioxidant pathways, with the highest dose of SOV 10 mg/kg having more significant (p < 0.001) results than the low dose of 5 mg/kg.

Combined Transcriptome and Circulating Tumor DNA Longitudinal Biomarker Analysis Associates With Clinical Outcomes in Advanced Solid Tumors Treated With Pembrolizumab.

Immune gene expression signatures are emerging as potential biomarkers for immunotherapy (IO). VIGex is a 12-gene expression classifier developed in both nCounter (Nanostring) and RNA sequencing (RNA-seq) assays and analytically validated across laboratories. VIGex classifies tumor samples into hot, intermediate-cold (I-Cold), and cold subgroups. VIGex-Hot has been associated with better IO treatment outcomes. Here, we investigated the performance of VIGex and other IO biomarkers in an independent data set of patients treated with pembrolizumab in the INSPIRE phase II clinical trial (ClinicalTrials.gov identifier: NCT02644369). Patients with advanced solid tumors were treated with pembrolizumab 200 mg IV once every 3 weeks. Tumor RNA-seq data from baseline tumor samples were classified by the VIGex algorithm. Circulating tumor DNA (ctDNA) was measured at baseline and start of cycle 3 using the bespoke Signatera assay. VIGex-Hot was compared with VIGex I-Cold + Cold and four groups were defined on the basis of the combination of VIGex subgroups and the change in ctDNA at cycle 3 from baseline (ΔctDNA). Seventy-six patients were enrolled, including 16 ovarian, 12 breast, 12 head and neck cancers, 10 melanoma, and 26 other tumor types. Objective response rate was 24% in VIGex-Hot and 10% in I-Cold/Cold. VIGex-Hot subgroup was associated with higher overall survival (OS) and progression-free survival (PFS) when included in a multivariable model adjusted for tumor type, tumor mutation burden, and PD-L1 immunohistochemistry. The addition of ΔctDNA improved the predictive performance of the baseline VIGex classification for both OS and PFS. Our data indicate that the addition of ΔctDNA to baseline VIGex may refine prediction for IO.

Internal Medicine and Internal Medicine-Pediatrics Residency Program Website Traffic Patterns Across Two Institutions and Five Electronic Residency Application Service (ERAS) Cycles.

Background Since the start of the COVID-19 pandemic in Spring 2020, medical residency program recruitment has become increasingly web-based due to the transition to virtual interviews. Although social media use by residency programs has soared during this time, applicant surveys show that official program websites remain the most used online resource. According to survey-based studies, the content that applicants favor on program websites tends to mirror their priorities in choosing programs. However, it is unclear whether applicant-reported priorities in program choice and website content truly drive program website traffic. In this analysis, we will elucidate website traffic patterns from two Internal Medicine residency programs and two Internal Medicine-Pediatrics programs, both in terms of the thematic content of high-traffic pages and changes in traffic patterns throughout the Electronic Residency Application Service (ERAS) application cycle. We will provide novel, data-driven guidance to residency program leadership regarding website content. Methodology For each of the four programs included in the analysis, total pageviews on a monthly basis were obtained for the annual ERAS application cycles taking place from 2017 through 2022. For one Internal Medicine program, data was only available for its current website from 2020 to 2022. The mean monthly pageviews were calculated for each page within each website. The total site traffic trends across each year and within high-traffic months were totaled as well. Results As expected, the highest traffic period for all programs in all years was the days before the application deadline, with a secondary, smaller spike in traffic around Match Day. In general, the most popular pages for all four programs were thematically in line with the top five applicant priorities in the 2022 National Resident Matching Program applicant survey, namely, geographic location, goodness of fit, program reputation, work/life balance, and current program residents. Three of the websites featured unique content that unexpectedly proved to be as popular as the top survey-reported topics, such as pages related to a new major clinical site, a new integrated subspecialty pathway, and, most profoundly, a pipeline program for certain applicants from groups that are underrepresented in medicine. Alumni career content was also heavily trafficked across all four programs. Conclusions Program directors should plan twice-yearly updates to residency program websites, timed to be finished by the start of the ERAS cycle in the fall, and again just before Match Day in March. Program directors should include specific, up-to-date information about unique program features. Future research should incorporate a more diverse variety of programs, software-based page content analysis, and traffic source data.

P-680 Comparison of ovarian hyperstimulation syndrome (OHSS) rates resulting from conventional dosing versus personalized dosing of follitropin delta in ovarian stimulation, analysis of RITA, ESTHER-1 trials

Abstract Study question To compare OHSS rates with conventional dosage of follitropin delta in the RITA-1 and RITA-2 trials (hereafter ‘RITA’) to personalized dosing in the ESTHER-1 trial. Summary answer RITA and ESTHER-1 had similar efficacy and OHSS rates despite differences in dosing regimens, possibly due to differences in fresh transfer cancellation rates. What is known already Follitropin delta is a human cell-line derived follicle stimulating hormone whose fixed dosage in ovarian stimulation, personalized based upon body weight and serum anti-Müllerian hormone (AMH) and body weight, has been shown to be safe and effective in Gonadotrophin Releasing Hormone (GnRH) antagonist ovarian stimulation protocols. In the present trial, conventional dosing of follitropin delta allowing for dose revisions has been evaluated in GnRH antagonist ovarian stimulation protocols to demonstrate the broad utility of this gonadotrophin therapeutic and to address United States (US) regulatory considerations. Study design, size, duration RITA were randomized, double-blind, controlled, US multicentre trials of follitropin delta. The primary endpoint was cumulative ongoing pregnancy rate after fresh/frozen transfers within 12 months of cycle start. 1058 women 18-42 years randomized 10:1 to follitropin delta or placebo. ESTHER-1 was a randomized, European multicentre, assessor-blind, noninferiority trial of follitropin delta. The primary endpoints were fresh transfer ongoing pregnancy and implantation rates. 1329 women 18-40 years randomized 1:1 to follitropin delta or follitropin alfa. Participants/materials, setting, methods In RITA, 12 µg/day, 15 µg/day dosages were used for 4 days: 18-34 or 35-42 years, respectively, with 3 µg dose adjustments thereafter depending on response. Human chorionic gonadotropin (hCG) was used if &amp;lt; 20 follicles of ≥ 12 mm and estradiol level &amp;lt;3,000 pg/mL. Else, agonist trigger and fresh transfer cancellation; ≥20 oocytes retrieved also cancelled fresh transfer. In ESTHER-1, hCG was used if &amp;lt; 25 follicles of ≥ 12 mm. Else, agonist trigger, and fresh transfer cancellation. Main results and the role of chance The ongoing pregnancy rate per fresh transfer with follitropin delta was 41.9% in RITA and 36.3% in ESTHER-1. The primary efficacy endpoint was met for all 3 trials. Rates and severity defined by Golan criteria of OHSS observed in RITA and ESTHER-1 were similar, respectively for: all OHSS, any grade (3.1% versus 3.5%), Grade 1 (0.3% versus 0.5%), Grade 2 (0.8% versus 0.9%), Grade 3 (1.8% versus 1.1%), Grade 4 (0.2% versus 0.6%), and Grade 5 (0.1% versus 0.5%). The rate of early OHSS, defined as onset ≤9 days after trigger of final follicular maturation, was also similar, respectively for any grade (2.2% versus 2.6%), Grade 1 (0.3% versus 0.3%), Grade 2 (0.6% versus 0.9%), Grade 3 (1.1% versus 0.8%), Grade 4 (0.1% versus 0.3%) and Grade 5 (0.1 % versus 0.3%). However, the fresh transfer cancellation rate was &amp;gt;3x higher in RITA (35.2%) than in ESTHER-1 (11.1%). Limitations, reasons for caution Other reasons for transfer cancellation in all trials included adverse events or no blastocyst available for transfer; however, no significant differences were observed. A placebo comparator was selected for RITA to meet regulatory requirements for double-blinding; women with ≤3 oocytes retrieved were offered support for treatment outside of the trials. Wider implications of the findings Stimulation with follitropin delta is effective and associated with low rates of OHSS when used with either conventional or personalized dosing. However, stricter criteria for the use of hCG as trigger and allowance of fresh transfer may be required with conventional dosing to maintain this safety profile. Trial registration number NCT01956110, NCT03740737, NCT03738618

Gait phase normalization resolves the problem of different phases being compared in gait cycle normalization

For time-continuous analysis of gait, the problem of variations in cycle durations is resolved by normalizing to the gait cycle, but results depend on the definition of the cycle start. Gait cycle normalization ignores variations in gait phase durations, which results in averaging and comparing data across different phases. We propose gait phase normalization as part of a comprehensive method for independently analyzing magnitude and timing differences. First, gait phases are identified and differences in absolute and/or relative timing of phase durations or any point of interest between conditions or groups are analyzed using standard statistics. Next, time-continuous gait data is normalized to gait phases, and statistical parametric mapping (SPM) is used to assess magnitude differences in gait data. This approach is demonstrated on data recorded from ten young healthy adults walking on a treadmill at five different speeds. Sagittal knee angle was normalized to gait cycle or gait phase using five different gait cycle start events. Walking at different speeds resulted in significant changes in gait phase durations, highlighting a problem ignored by gait cycle normalization. SPM results for knee angle normalized to gait cycle varied from normalization to gait phases. Gait phase normalized SPM results were robust to the definition of the cycle start, in contrast to gait cycle normalized data. The approach of analyzing phase durations and normalizing data to gait phases overcomes previous limitations and enables a comprehensive analysis of magnitude and timing differences in time-continuous gait data and could be readily adapted to other tasks.

تقدير الكفاءة الاقتصادية والفنية لمشاريع تسمين العجول في محافظة واسط للعام 2022

Calf breeding and fattening projects in general are considered the main source of meat production in Iraq. This vital and widespread sector is considered the largest in Wasit Governorate. There are a significant number of fields specialized in raising and fattening calves. Despite the increase in production that the owners of these fields have experienced, these Owners face difficulties in obtaining expensive feed and poor vaccines, veterinary services and treatments imported and controlled by the private sector, which has led to high economic costs. Calf fattening projects have similar social and economic advantages. Calf fattening, which is a sub-sector of the livestock sector, has an important role in transforming... Calves turn into high-quality and efficient beef through economic use. Increased live weight, feed intake, feed efficiency and capacity, and the relationship between profitability are direct factors on calf breeding and fattening projects. The results showed that the total costs (fixed and variable) for the average projects in the sample amounted to approximately (136,779) one hundred and thirty-six million, seven hundred and seventy-nine thousand Iraqi dinars. Through the results, it was shown that the variable costs have a greater relative importance in the calf rearing and fattening projects in the study area than the fixed costs, and the other costs are due to the prices of the calves upon purchase (before the start of the fattening cycle), so their percentage reached (61.46%) of the total total costs, while the cost amounted to (61.46%). Net sale of one calf after fattening (2009000) is two million and nine thousand dinars The economic efficiency and its components for the calf rearing and fattening projects in the study sample were estimated using the DEAP data envelopment analysis method and according to the cost function variables in light of the resources used and their prices assuming changing returns to scale. The economic efficiency and its components, both the technical and Allocative efficiency of the calf breeders in the study sample, were estimated using the data envelopment analysis method (DEAP), and the results of the estimates of economic (EE), technical (TE), and Allocative (AE) efficiency were confirmed. By reviewing these results, it was found that the level of technical efficiency of the study sample ranged Between a minimum of about 72.4%) and a maximum of 100%), with an average of (97.5%). As for the number of fields that achieved full efficiency (100%), it reached 30 fields, and a percentage of (60%) was formed. As for the fields that achieved efficiency between (%80-100%) reached (49) fields, and as for the fields that achieved technical efficiency (72.4%), it was one field.

N9: Pilot study of novel shortened induction for high-risk neuroblastoma.

10052 Background: N9 induction for high-risk neuroblastoma was designed to limit non-hematological toxicity (especially ototoxicity) and to prevent relapse in the central nervous system (CNS). N9 builds on 2 novel regimens: high-dose cyclophosphamide-topotecan-vincristine (CTV) and ifosfamide-carboplatin-etoposide (ICE), each with good penetration across the blood-brain barrier. Methods: N9 is a pilot study (Clinicaltrials.gov.NCT04947501) to assess feasibility and safety. Secondary/exploratory objectives include response, collection of peripheral blood stem cells (PBSCs; ≥5x106/kg CD34(+) cells sufficient for ≥2 rescues), tumor resection, and assessment of central nervous system relapse. Early stopping rules centered on excessive delay in timing of chemotherapy. Eligibility criteria included age &gt;1-to-&lt;13 years; 1 prior chemotherapy cycle was allowed. CTCAE Version 5.0 and International Neuroblastoma Response Criteria are used.N9 comprises 4 cycles of chemotherapy. Cycles start after absolute neutrophil count is &gt;500/μL, platelets &gt;100,000/μL, and non-hematologic toxicities grade ≤2. Intervals of 21-28 days between start of cycles are foreseen. PBSC collection and surgery follow &gt;3 cycles. Cycles #1 and #4 (CTV): cyclophosphamide 70mg/kg/day, days 1-2, topotecan 2mg/m2/day, days 1-4, and vincristine 0.067mg/kg, day 1. Cycle #2 (ICE): ifosfamide 1500mg/m2/day, days 1-5, carboplatin 400mg/m2/day, days 1-2, and etoposide 100mg/m2/day, days 1-5. Cycle #3: cyclophosphamide (as in CTV) and 72-hr infusions of doxorubicin 75mg/m2 and vincristine 0.067mg/kg. Results: The target number of 15 patients were enrolled: 10/2021-9/2023; age 1.5–9.8 (median 3.3) years; 14 stage M, 1 stage L2; and 10 post-1 cycle of other chemotherapy. They completed N9 without undue toxicity: all cycles started on time, organ functions remained intact, 11/11 patients tested had no ototoxicity, and acute toxicities were typical for myelosuppression (including uncomplicated fever/neutropenia). Responses were complete (n=6), partial (n=5), and stable disease (n=4). The target number of PBSCs was collected in 12 patients (9-75, median 14 x106/kg CD34(+) cells), 4x106/kg in 2 patients, and pending in 1. All patients had gross total resections of the primary tumor. Post-N9, patients did not undergo transplant, but proceeded to immunotherapy (naxitamab) or chemoimmunotherapy (naxitamab+irinotecan-temozolomide). Of 9 with residual disease post-N9, 7 achieved CR (median of 5.6 months from study entry) and 1 achieved metabolic CR (16 months), though 3 subsequently relapsed (no CNS). Conclusions: N9 shows promise for reducing chemotherapy and long-term toxicity. Less chemotherapy without compromising survival is a realistic goal by virtue of the advances with anti-GD2 monoclonal antibodies which, in combination with GM-CSF+low-dose chemotherapy, are highly effective against chemo-resistant disease in bone/bone marrow. Clinical trial information: NCT04947501 .

Viral hepatitis screening in patients with early breast cancer receiving cancer therapy: A quality improvement initiative.

11125 Background: ASCO guidelines recommend screening all patients for hepatitis B virus (HBV) before initiation of cancer therapy. Comprehensive screening for HBV includes measuring HBV surface antigen (HBsAg), HBV core antibody (anti-HBc), and antibody to HBV surface antigen (anti-HBs). ASCO also recommends hepatitis C virus (HCV) screening in patients with cancer. Cancer patients receiving cancer therapy represent a vulnerable population and reactivation of undetected hepatitis virus can lead to devastating consequences such as liver failure and death. At MD Anderson Cancer Center, rates of hepatitis screening for all cancer patients has been historically low. For example, rates are around 29% for HBV screening in patients receiving cancer therapy in 2019-2021. The aim of this quality improvement study is to increase rates of HBV and HCV screening in early breast cancer patients in the Breast Medical Oncology clinic at MD Anderson before undergoing cancer therapy to at least 50%. Methods: Quality improvement measures were implemented by 1) creation of an order panel in the electronic medical record (EMR) which contains all tests needed for comprehensive HBV and HCV screening (HBsAg, anti-HBc, HBsAb, and anti-HCV), and 2) an educational session to providers in the Breast Medical Oncology clinics. Data was collected for patients seen at MD Anderson initiating cancer therapy (start of cycle 1) between April 1, 2023 until September 30th, 2023. Inclusion criteria were early breast cancer patients (Stage I-III) and receiving chemotherapy at MD Anderson. Exclusion criteria were Stage IV disease, or those receiving chemotherapy at an outside institution. Results: A total of 340 patients were screened, and 219 were determined to meet inclusion criteria for data extraction. In total, 105 patients (48%) received comprehensive HBV screening, with 137 (63%) receiving at least one HBV test. A total of 122 (56%) patients were screened for HCV. Combining data for both HBV and HCV, 88 (40%) received both comprehensive HBV and HCV screening (HBsAg, anti-HBc, anti-HBs, anti-HCV). A majority of patients (91% for HBV and 93% for HCV) were screened prior to cycle 1 of cancer therapy. The EMR order panel was utilized in 51 (23%) of patients. Anti-HBc was positive in 8 of those tested, and HBsAg was positive in 1 patient. No patients tested positive for HCV. Conclusions: Screening rates for HBV and HCV individually were near or exceeded our goal, however rates of combined HBV and HCV screening were lower. Going forward, additional education to providers as well as increased awareness of the available order panel will be needed to ensure we are comprehensively screening for both HBV and HCV in our patients. [Table: see text]

Impact of chemotherapy-induced peripheral neuropathy permanence on patients' preference to discontinue chemotherapy.

12046 Background: Chemotherapy-induced peripheral neuropathy (CIPN) diminishes patients’ functional ability and quality of life; approximately 40% of patients experience CIPN symptoms 3 years after treatment. Due to the absence of effective CIPN treatments, ASCO guidelines recommend discontinuing chemotherapy in patients experiencing intolerable CIPN symptoms. Little is known about patient’s preference to continue or discontinue chemotherapy when experiencing CIPN, and whether the potential permanence of CIPN symptoms affects this decision. The objective of this prospective observational study was to determine the effect of CIPN symptom permanence on patients’ preference to discontinue chemotherapy. Methods: Patients receiving taxane and/or platinum chemotherapy for breast or colorectal cancer were enrolled in a prospective observational clinical study. Patients reported their CIPN severity using the EORTC CIPN20 patient-reported outcome questionnaire at the start of each treatment cycle. At the same time, patients were asked if they would prefer to continue or discontinue chemotherapy treatment under the hypothetical scenario that their current CIPN symptoms would be temporary or permanent. A generalized linear mixed effects model was used to determine the effect of CIPN severity, permanence, and other clinical variables on a patient’s decision to discontinue (vs. continue) chemotherapy treatment. Results: A total of 66 patients completed data collection at least one time, of whom 55 (83%) had breast cancer, 12 (18%) had metastatic disease, and 52 (79%) received a taxane. The odds a patient would prefer to discontinue chemotherapy treatment if their CIPN symptoms would be permanent (vs. temporary) were nearly 30 times greater (odds ratio (OR)=30.15, 95% confidence interval (CI): 15.73-57.79, p&lt;0.001, Table). There was a statistical trend toward preferring to discontinue chemotherapy treatment as CIPN symptom severity increased (OR=1.09, 95% CI: 1.00-1.19, p=0.063). Conclusions: The potential for CIPN symptoms to be permanent has a huge effect on whether patients want to continue or discontinue chemotherapy treatment. Additional data is needed on the incidence and predictors of permanent CIPN. More importantly, shared decision-making tools that convey the risk of permanent CIPN, and the potential risk of discontinuing chemotherapy treatment, are needed to facilitate patient-centered treatment decisions so that each patient with cancer achieves their personal treatment goals. [Table: see text]

Quantifying lumbar mobility using a single tri-axial accelerometer

BackgroundLumbar mobility is regarded as important for assessing and managing low back pain (LBP). Inertial Measurement Units (IMUs) are currently the most feasible technology for quantifying lumbar mobility in clinical and research settings. However, their gyroscopes are susceptible to drift errors, limiting their use for long-term remote monitoring. Research questionCan a single tri-axial accelerometer provide an accurate and feasible alternative to a multi-sensor IMU for quantifying lumbar flexion mobility and velocity? MethodsIn this cross-sectional study, 18 healthy adults performed nine repetitions of full spinal flexion movements. Lumbar flexion mobility and velocity were quantified using a multi-sensor IMU and just the tri-axial accelerometer within the IMU. Correlations between the two methods were assessed for each percentile of the lumbar flexion movement cycle, and differences in measurements were modelled using a Generalised Additive Model (GAM). ResultsVery high correlations (r > 0.90) in flexion angles and velocities were found between the two methods for most of the movement cycle. However, the accelerometer overestimated lumbar flexion angle at the start (-4.7° [95 % CI -7.6° to -1.8°]) and end (-4.8° [95 % CI -7.7° to -1.9°]) of movement cycles, but underestimated angles (maximal difference of 4.3° [95 % CI 1.4° to 7.2°]) between 7 % and 92 % of the movement cycle. For flexion velocity, the accelerometer underestimated at the start (16.6°/s [95%CI 16.0 to 17.2°/s]) and overestimated (-12.3°/s [95%CI -12.9 to -11.7°/s]) at the end of the movement, compared to the IMU. SignificanceDespite the observed differences, the study suggests that a single tri-axial accelerometer could be a feasible tool for continuous remote monitoring of lumbar mobility and velocity. This finding has potential implications for the management of LBP, enabling more accessible and cost-effective monitoring of lumbar mobility in both clinical and research settings.

Protocol change improves live birth and recurrent cycle cancellation rates after a previous IVF cycle cancellation: an analysis of 13000 autologous cycles reported to SART CORS.

After an IVF cycle cancellation, does changing the stimulation protocol affect the odds of live birth and recurrent cancellation in the subsequent cycle? After IVF cycle cancellation, compared to those who repeated the same stimulation protocol, those who changed their protocol had higher odds of live birth and lower odds of recurrent cycle cancellation. There is limited data addressing the effect of changing the stimulation protocol after an IVF cycle is cancelled during initial stimulation. The odds of live birth outcomes are not known so far in studies addressing the effect of changing the protocol. Retrospective Cohort Study using the 2014-2017 Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database. The data included 13135 patients with a first autologous IVF cycle that resulted in a cycle cancellation and was followed by a second autologous cycle within the study period. We excluded fertility preservation cycles, supernumerary cycle attempts after the second IVF cycle attempt, and cycles with more than one stimulation protocol documented per cycle start. Patients who received the same protocol for both cycles (n = 6434) were compared to those who changed their protocol in the second cycle (n = 6701). Multivariable logistic regression analyses were performed to estimate the adjusted odds of live birth and recurrent cancellation. Changing the protocol in the second cycle resulted 14% lower odds of recurrent cycle cancellation (P = 0.01) and 17% higher odds of live birth after fresh transfers (P = 0.04). When stratifying the data by specific combinations of protocol change (agonist flare, agonist suppression, antagonist), there was an increase in live birth when switching from antagonist to agonist suppression (odds ratio (OR) = 1.36, P = 0.03) and from agonist suppression to antagonist (OR = 1.73, P = 0.01) compared to those who repeated their same stimulation protocol. Specifically in poor responders, outcomes were worse when using the agonist flare protocol and significantly improved with the agonist suppression protocol. Comparison of response to stimulation between first and second cycles cannot be made in this study because the index IVF cycle was cancelled during ovarian stimulation, and thus there is no reportable outcome data for that cycle. Additionally, SART only tracks the three stimulation protocols addressed in this study and does not have data on more contemporary protocols that are used in poor responders thus limiting the generalizability of our findings. Using the SART CORS database, which includes >90% of all reported IVF cycles in the USA, provides generalizability to the demographically diverse IVF populations found here. In agreement with prior studies assessing change in IVF protocols, the agonist flare protocol seems to result in worse IVF outcomes, and based on our results, we believe that there is no role for the agonist flare protocol in patients with a prior poor response to stimulation. None declared. N/A.

Real-World Pharmacokinetics, Effectiveness, and Safety of Atezolizumab in Patients With Unresectable Advanced or Recurrent NSCLC: An Exploratory Study of J-TAIL

IntroductionThis study validated real-world pharmacokinetic (PK) data using an established population PK (PopPK) model for atezolizumab in Japanese patients with NSCLC and explored the relationship between PK parameters, effectiveness, and adverse events (AEs) for the 1200 mg once every three weeks regimen. MethodsA subgroup of 262 of 1039 patients from J-TAIL consented to this exploratory research for PK evaluation of atezolizumab monotherapy for unresectable advanced/recurrent NSCLC (August 2018 to October 2019; 197 institutions). We evaluated plasma concentrations before the start of the third cycle of atezolizumab infusion classified into quartiles 1 to 4, their association with effectiveness, and the association between atezolizumab maximum plasma concentrations (Cmax) calculated using the existing PopPK model and AEs of special interest (AESIs). ResultsOverall, 175 of 262 patients were included; baseline characteristics were similar to those of patients enrolled in J-TAIL (Eastern Cooperative Oncology Group performance status ≥ 2, 12.0%; age ≥ 75 y, 28.9%; atezolizumab as more than or equal to third-line treatment, 57.5%). Atezolizumab plasma concentrations were similar to previously reported data among Japanese/non-Japanese patients. The overall survival was significantly shorter in patients with lower atezolizumab plasma concentrations in Q1 versus Q2 to Q4, although progression-free survival remained the same. The PK data adequately fit the PopPK model, with the frequency of AESIs increasing as the calculated Cmax at cycle 1 increased. ConclusionsIn real-world Japanese patients with unresectable advanced/recurrent NSCLC, PKs were similar to previous reports. Certain patient populations had shorter overall survival, and atezolizumab plasma concentrations in cycle 3 were lower in this population. Elevated Cmax at cycle 1 may be associated with an increased frequency of AESIs.

Variation in the timing and duration of autumn leaf phenology among temperate deciduous trees, native shrubs and non-native shrubs.

The timing and duration of autumn leaf phenology marks important transitions in temperate deciduous forests, such as, start of senescence, declining productivity and changing nutrient cycling. Phenological research on temperate deciduous forests typically focuses on upper canopy trees, overlooking the contribution of other plant functional groups like shrubs. Yet shrubs tend to remain green longer than trees, while non-native shrubs, in particular, tend to exhibit an extended growing season that confers a competitive advantage over native shrubs. We monitored leaf senescence and leaf fall (2017-2020) of trees and shrubs (native and non-native) in an urban woodland fragment in Wisconsin, USA. Our findings revealed that, the start of leaf senescence did not differ significantly between vegetation groups, but leaf fall started (DOY 273) two weeks later in shrubs. Non-native shrubs exhibited a considerably delayed start (DOY 262) and end of leaf senescence (DOY 300), with leaf-fall ending (DOY 315) nearly four weeks later than native shrubs and trees. Overall, the duration of the autumn phenological season was longer for non-native shrubs than either native shrubs or trees. Comparison of the timing of spring phenophases with the start and end of leaf senescence revealed that when spring phenology in trees starts later in the season senescence also starts later and ends earlier. The opposite pattern was observed in native shrubs. In conclusion, understanding the contributions of plant functional groups to overall forest phenology requires future investigation to ensure accurate predictions of future ecosystem productivity and help address discrepancies with remote sensing phenometrics.

Comparative study of wastewater treatment efficiency: ozone vs. atmospheric oxygen with a manganese dioxide catalyst

Abstract This study aims to validate the wastewater treatment technique and compare the effectiveness of applying an ozone mixture and atmospheric oxygen in the presence of a catalyst (manganese dioxide) with various dosages. A total of 540 replicates were performed, corresponding to different levels of manganese dioxide concentrations during oxygen and ozone delivery (270 repetitions for each of the experiments). The research was carried out using an experimental setup developed by the authors. The maximum efficiency of oxidation processes was observed within 15–30 min after the start of the treatment cycle. The decrease in the level of chemical oxygen demand within the first quarter-hour during ozone treatment was significantly greater compared to atmospheric oxygen treatment (p ≤ 0.05). The method's efficiency increased to 53% for ozone and 41% for oxygen after 30 min of purification (p ≤ 0.05). Lower catalyst consumption was observed when using an ozone mixture. The tested technology can be recommended for wastewater treatment with high hydrocarbon concentrations. The findings of the study indicated the potential application of ozone treatment with a manganese catalyst for treating wastewater with high hydrocarbon content, thereby fostering the development of more effective water purification methods in the industrial sector.

End-of-treatment 18[F]-FDG PET can predict early progression in patients receiving bendamustine-rituximab for follicular lymphoma in first relapse: a prospective West Japan hematology Study Group (W-JHS) NHL01 trial.

Response determined by 18[F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)-CT after induction therapy can predict progression-free survival (PFS) in follicular lymphoma (FL). However, little prospective research has examined the significance of PET after second-line therapy. We conducted a prospective multicenter phase II trial (W-JHS NHL01) of bendamustine plus rituximab (BR) without rituximab maintenance for FL in first relapse. This study aimed to evaluate the usefulness of end-of-treatment (EOT)-PET for predicting PFS in FL patients in first relapse. EOT-PET examinations were performed between 6 and 8weeks from the start of the last BR cycle. The primary endpoint was 1-year PFS. Key secondary endpoints were overall response rate (ORR), complete response rate (CRR), and 1-year overall survival (OS). Seventy-five patients were enrolled, and 8 were excluded from analysis. ORR was 86.6% and CRR was 59.7%. One-year PFS was 88.9% (95% confidence interval [CI] 80.7-94.3%) and 1-year OS in 75 patients was 97.3% (95% CI 89.6-99.3%). One-year PFS was significantly inferior in EOT-PET-positive patients (n = 9) compared with PET-negative patients (n = 58) (77.8% vs. 93.1%; p = 0.02). We confirmed that EOT-PET after second-line BR therapy could predict early progression in FL patients in first relapse.

Low δ18O and δ30Si TTG at ca. 2.3 Ga Hints at an Intraplate Rifting Onset of the Paleoproterozoic Supercontinent Cycle

AbstractThe start of the Paleoproterozoic supercontinent cycle is typically taken as the initiation of orogenesis at ca. 2.1 Ga leading to the assembly of Earth's first supercontinent, Columbia. However, the dearth of ca. 2.5–2.2 Ga geological records makes it difficult to deduce tectonic factors during the onset of the Paleoproterozoic supercontinent cycle. The petrogenesis of tonalite–trondhjemite–granodiorite (TTG) provides useful proxies for tracing prevailing geodynamic regimes of early continental evolution. However, marked decreases of TTG and other magmatism occurred across the Archean–Paleoproterozoic transition and have previously precluded forming testable hypotheses. Early Paleoproterozoic TTGs have been identified in the North China Craton (NCC) and other cratons, which may represent the last major pulse of TTGs globally. Here we present low δ18O and δ30Si ca. 2.3 Ga TTGs from the NCC, together with thermodynamic modeling and compilation of stable O and Si isotopes for TTGs globally through time. The ca. 2.3 Ga TTGs were derived from the partial melting of Archean basaltic crust and give lighter average zircon δ18O (3.15 ± 0.35‰) and whole‐rock δ30Si values (−0.17 ± 0.08‰) than most Archean TTGs. Considering coeval mafic‐felsic igneous rocks, and lithospheric thinning since ca. 2.5 Ga based on estimated crustal thickness through the Neoarchean–Paleoproterozoic, we posit the onset of an intraplate rifting consistent with the anomalous low‐δ18O magmatism. Continental rifting of Archean cratons/supercratons plausibly hints at the formation of rifts driving subduction initiation as the veritable onset of the Paleoproterozoic supercontinent cycle.