Mean Percentage Research Articles

Safety, tolerability, pharmacokinetics, and pharmacodynamics of TG103 injection in participants who are overweight or obese: a randomized, double-blind, placebo-controlled, multiple-dose phase 1b study

BackgroundTG103, a glucagon-like peptide-1 analog, is being investigated as an option for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of TG103 injection in participants who are overweight or obese without diabetes.MethodsIn this randomized, double-blind, placebo-controlled, multiple-dose phase 1b study, participants aged 18–75 years with a body-mass index (BMI) ≥ 26.0 kg/m2 and body weight ≥ 60 kg were enrolled from three centers in China. The study included three cohorts, and in each cohort, eligible participants were randomly assigned (3:1) to one of three once-weekly subcutaneous TG103 groups (15.0, 22.5 and 30.0 mg) or matched placebo, without lifestyle interventions. In each cohort, the doses of TG103 were escalated in 1-week intervals to the desired dose over 1 to 4 weeks. Then participants were treated at the target dose until week 12 and then followed up for 2 weeks. The primary endpoint was safety and tolerability assessed by the incidence and severity of adverse events (AEs) from baseline to the end of the follow-up period. Secondary endpoints included pharmacokinetic and pharmacodynamic profiles of TG103 and the occurrence of anti-drug antibodies to TG103.ResultsA total of 147 participants were screened, and 48 participants were randomly assigned to TG103 (15.0, 22.5 and 30.0 mg groups, n = 12 per group) or placebo (n = 12). The mean (standard deviation, SD) age of the participants was 33.9 (10.0) years; the mean bodyweight was 81.65 (10.50) kg, and the mean BMI was 29.8 (2.5) kg/m2. A total of 466 AEs occurred in 45 of the 48 participants, with 35 (97.2%) in the TG103 group and 10 (83.3%) in the pooled placebo group. Most AEs were grade 1 or 2 in severity, and there were no serious adverse events (SAEs), AEs leading to death, or AEs leading to discontinuation of treatment. The steady-state exposure of TG103 increased with increasing dose and was proportional to Cmax,ss, AUCss, AUC0-t and AUC0-inf. The mean values of Cmax,ss ranged from 951 to 1690 ng/mL, AUC0-t ranged from 150 to 321 μg*h/mL, and AUC0-inf ranged from 159 to 340 μg*h/mL. TG103 had a half-life of 110–116 h, with a median Tmax of 36–48 h. After treatment for 12 weeks, the mean (SD) values of weight loss from baseline in the TG103 15.0 mg, 22.5 mg and 30.0 mg groups were 5.65 (3.30) kg, 5.35 (3.39) kg and 5.13 (2.56) kg, respectively, and that in the placebo group was 1.37 (2.13) kg. The least square mean percent weight loss from baseline to D85 in all the TG103 groups was more than 5% with p < 0.05 for all comparisons with placebo.ConclusionsIn this trial, all three doses of once-weekly TG103 were well tolerated with an acceptable safety profile. TG103 demonstrated preliminary 12-week body weight loss without lifestyle interventions, thus showing great potential for the treatment of overweight and obesity.Trial registrationClinicalTrials.gov, NCT04855292. Registered on April 22, 2021.

Implementation of Evacuation Management Plan of a Rural Barangay in Surigao Del Norte, Philippines

This descriptive quantitative study evaluated the extent of evacuation management plan implementation as experienced by the residents of Brgy. Poblacion, San Francisco, Surigao del Norte. The respondents were 123 residents and were selected through convenient sampling. The data gathered were analyzed and treated using the following descriptive statistical tools: frequency count and percentage distribution, mean and standard deviation, and analysis of variance (ANOVA). Results showed that the camp coordination and management plan was moderately implemented. This suggests that while the plan is being implemented to some extent, there is room for improvement to ensure a more effective and robust evacuation process in the future. In addition, the findings showed a significant degree of difference in the perceived implementation extent of the evacuation phase with respect to the respondents’ years of residency, indicating that length of stay may impact residents’ knowledge, familiarity with the area, and ability to contribute to the community’s resilience during evacuations. Finally, it was recommended that implementing the recommended strategies, actions and proposed enhancement plan can have a transformative impact on the barangay’s camp coordination and management plan.

Knowledge, Attitudes, and Beliefs of Paulinian College Students about Diabetes

The main purpose of the study was to evaluate the degree of knowledge, attitudes, and beliefs of Paulinian college students on diabetes for appropriate plans and interventions. The participants were 218 Paulinian college students at St. Paul University Surigao during the academic year 2022-2023. The study employed a quantitative descriptive research design involving the use of a researcher-made survey questionnaire that underwent validation and pilot testing. The data gathered were analyzed and treated by using the following descriptive statistical tools: frequency count and percentage distribution, mean and standard deviation, analysis of variance (ANOVA), and Shapiro-Wilk test. Results showed that the college students had a significant degree of difference in the level of respondent’s attitudes and beliefs on Diabetes based on behavior formation and belief generation when grouped according to age, sex, and socio-economic status. Students had significant differences in their attitudes and beliefs when grouped as to their knowledge as there was found to be a correlation between attitudes and beliefs. Generally, the findings showed that there is a significant degree of difference in the level of respondent’s knowledge, attitudes, and beliefs. It was recommended to provide an action plan as a health education strategy according to their knowledge about Diabetes for a continuum favorable attitude of students and change their beliefs on a more scientific approach and analyze deeply the misconceptions regarding the disease.

Adherence to Hypertension Management Practices Based on International Society of Hypertension (ISH) Guidelines among Hypertensive Patients

Hypertension is a significant global health concern with profound cardiovascular implications. The researchers used a quantitative research design employing a descriptive research survey approach and the instrument used to seek information was a researcher-made questionnaire for assessing demographic characteristics, adherence to hypertension management such as medication adherence, lifestyle changes, and blood pressure control. These tools were used in data analysis frequency count and percentage distribution, mean and standard deviation, and lastly analysis of variance (ANOVA). This abstract presents a study conducted in Brgy. Washington, Surigao City, focusing on adherence to hypertension management guidelines by the International Society of Hypertension (ISH). Respondents generally showed high adherence to hypertension management, primarily taking medicine, with moderate adherence to monitoring blood pressure, physical activity, and diet, influenced by demographic factors. The study found no significant difference in medication adherence or adherence to a balanced diet among hypertensive individuals in Brgy. Washington, but did show differences based on age, occupation, income, and years of hypertension, emphasizing the need for community-based initiatives.

Plozasiran, an RNA Interference Agent Targeting APOC3, for Mixed Hyperlipidemia.

Persons with mixed hyperlipidemia are at risk for atherosclerotic cardiovascular disease due to an elevated non-high-density lipoprotein (HDL) cholesterol level, which is driven by remnant cholesterol in triglyceride-rich lipoproteins. The metabolism and clearance of triglyceride-rich lipoproteins are down-regulated through apolipoprotein C3 (APOC3)-mediated inhibition of lipoprotein lipase. We carried out a 48-week, phase 2b, double-blind, randomized, placebo-controlled trial evaluating the safety and efficacy of plozasiran, a hepatocyte-targeted APOC3 small interfering RNA, in patients with mixed hyperlipidemia (i.e., a triglyceride level of 150 to 499 mg per deciliter and either a low-density lipoprotein [LDL] cholesterol level of ≥70 mg per deciliter or a non-HDL cholesterol level of ≥100 mg per deciliter). The participants were assigned in a 3:1 ratio to receive plozasiran or placebo within each of four cohorts. In the first three cohorts, the participants received a subcutaneous injection of plozasiran (10 mg, 25 mg, or 50 mg) or placebo on day 1 and at week 12 (quarterly doses). In the fourth cohort, participants received 50 mg of plozasiran or placebo on day 1 and at week 24 (half-yearly dose). The data from the participants who received placebo were pooled. The primary end point was the percent change in fasting triglyceride level at week 24. A total of 353 participants underwent randomization. At week 24, significant reductions in the fasting triglyceride level were observed with plozasiran, with differences, as compared with placebo, in the least-squares mean percent change from baseline of -49.8 percentage points (95% confidence interval [CI], -59.0 to -40.6) with the 10-mg-quarterly dose, -56.0 percentage points (95% CI, -65.1 to -46.8) with the 25-mg-quarterly dose, -62.4 percentage points (95% CI, -71.5 to -53.2) with the 50-mg-quarterly dose, and -44.2 percentage points (95% CI, -53.4 to -35.0) with the 50-mg-half-yearly dose (P<0.001 for all comparisons). Worsening glycemic control was observed in 10% of the participants receiving placebo, 12% of those receiving the 10-mg-quarterly dose, 7% of those receiving the 25-mg-quarterly dose, 20% of those receiving the 50-mg-quarterly dose, and 21% of those receiving the 50-mg-half-yearly dose. In this randomized, controlled trial involving participants with mixed hyperlipidemia, plozasiran, as compared with placebo, significantly reduced triglyceride levels at 24 weeks. A clinical outcomes trial is warranted. (Funded by Arrowhead Pharmaceuticals; MUIR ClinicalTrials.gov number NCT04998201.).

Corrected Aggregate Workload approach on order release by considering job’s routing position induced variable indirect load

Purpose Workload contribution calculation approaches in the existing literature overestimate or underestimate indirect workload, which increases both workload fluctuation and shop floor throughput performance. This study optimizes a Corrected Aggregate Workload (CAW) approach to control the workload contribution of workstations and Work In Progress (WIP) levels, thereby improving the shop floor throughput performance.Design/methodology/approach This study adopts simulation experiment by SimPy, and experimental factors are: (1) two workload contribution methods (CAW method and considering Position Corrected Aggregate Workload [PCAW] method); (2) two release methods (LUMS COR release and immediate release); (3) eleven workload norms for LUMS COR release (from 7- to 15-time units), and infinite workload norm for immediate release; and (4) two dispatching rules (First Come First Served, FCFS and Operation Due Date, ODD). Each scenario is replicated 100 times, and for each replication data are collected for 10,000 time units, being the warm-up period set to 3,000-time units.Findings The results of this study confirm that the PCAW calculation method outperforms the CAW method, especially during higher workload norm levels. The PCAW method is considered the better solution in practice due to its excellent performance in terms of percentage tardiness and mean tardiness time. The efficient workload contribution approach, as discussed in this study, has the potential to offset delivery performance loss that results from throughput performance loss.Originality/valueThis study proposes a novel approach that considers the workstations’ position in the routing of the job and the position of jobs CAW method. The results demonstrated that it allows shop floor throughput time to be short and feasible. It controls WIP by workload contribution of workstations, resulting in a lean shop floor. Therefore, workload contribution calculation is of particular significance for high-variety Make-To-Order (MTO) companies.

Stereotactic central/core ablative radiation therapy: results of a phase I study of a novel strategy to treat bulky tumor

PurposeBulky tumor remains as a challenge to surgery, chemotherapy and conventional radiation therapy. Hence, in efforts to overcome this challenge, we designed a novel therapeutic paradigm via strategy of Stereotactic Central/Core Ablative Radiation Therapy (SCART).), which is based on the principles of SBRT (stereotactic body radiation therapy and spatially fractionated radiation therapy (SFRT). We intend to safely deliver an ablative dose to the core of the tumor and with a low dose at tumor edge. The purpose of the phase 1 study was to determine dose-limiting toxicities (DLT)s and the Maximum Tolerated Dose (MTD) of SCART.Methods and materialsWe defined a SCART-plan volume inside the tumor, which is proportional to the dimension of tumor. VMAT/Cyberknife technique was adopted. In the current clinical trial; Patients with biopsy proven recurrent or metastatic bulky cancers were enrolled. The five dose levels were 15 Gy X1, 15Gy X3, 18GyX3, 21GyX3 and 24GyX3, while keeping the whole tumor GTV’s border dose at 5Gy each fraction. There was no restriction on concurrent systemic chemotherapy agents.Results21 patients were enrolled and underwent SCART. All 21 patients have eligible data for study follow-up. Radiotherapy was well tolerated with all treatment completed as scheduled. The dose was escalated for two patients to 24GyX3. No grade 3 or higher toxicity was observed in any of the enrolled patients. The average age of patients was 66 years (range: 14–85) and 13 (62%) patients were male. The median SCART dose was 18Gy (range: 15 - 24). Six out of the 18 patients with data for overall survival (OS) died, and the median time to death was 16.3 months (range: 1 - 25.6). The mean percent change for tumor shrinkage between first visit volumes and post-SCART volumes was 49.5% (SD: 40.89, p-value:0.009).ConclusionSCART was safely escalated to 24 GyX 3 fractions, which is the maximum Tolerated Dose (MTD) for SCART. This regimen will be used in future phase II trials.

#366 Humanistic burden of immunoglobulin A nephropathy and focal segmental glomerulosclerosis on patients and care-partners (HONUS): results for Europe

Abstract Background and Aims Rare proteinuric kidney diseases are associated with clinical and economic burden, however, the humanistic burden associated with these conditions has not been directly evaluated. HONUS is a multi-national, cross-sectional survey study designed to evaluate the humanistic burden associated with two rare kidney diseases, immunoglobulin A nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS), from the patient and caregiver perspectives in the United States and Europe. The current analysis presents preliminary results from adults with IgAN or FSGS and their care-partners in Spain, Germany, France, or the United Kingdom. Method The study recruited adult patients (≥ 18 years old) with IgAN or FSGS and their adult care-partners. Participants completed an online survey including demographic and clinical characteristics, health-related quality of life (HRQoL) (i.e., Kidney Disease Quality of Life Instrument [KDQoL] including 12-Item Short Form Survey [SF-12]), anxiety and depression (i.e., Generalized Anxiety Disorder Assessment [GAD-7], Patient Health Questionnaire [PHQ-9]), and disease impact on work productivity (i.e., Work Productivity and Activity Impairment [WPAI]). Descriptive analyses were conducted. Results From Europe, 26 IgAN patients, 9 FSGS patients, and their care-partners (4 IgAN and 2 FSGS patients did not report having a care-partner) participated in the survey before November 2023. Mean age for IgAN and FSGS patients was 42.2 years and 51.4 years, with 61.5% and 44.4% being female, respectively. Over two-fifths of both IgAN (42.3%) and FSGS patients (44.4%) were in chronic kidney disease (CKD) stage 3, 4 or 5 (on dialysis), while over one-quarter had received a kidney transplant (IgAN: 26.9%; FSGS: 44.4%). Most patients had worse CKD status since diagnosis (IgAN: 61.5%; FSGS: 77.8%). Hypertension and anemia were the most common comorbidities in both groups. In terms of HRQoL, mean (SD) SF-12 physical and mental component scores (PCS, MCS) indicated IgAN patients were more impacted on the mental component (PCS: 47.3 [11.6], MCS: 43.2 [10.9]), with FSGS patients more impacted on the physical component (PCS: 40.6 [6.0], MCS: 43.8 [9.1]), reflecting generally worse HRQoL (lower scores) than previously published European general population scores (50.0 for PCS and MCS). Moderate to severe anxiety was reported by 30.8% of IgAN and 33.3% of FSGS patients, and moderate to severe depression by 30.8% of IgAN and 44.4% of FSGS patients. Among employed IgAN patients (69.2%), mean percent absenteeism (work time missed) was reported at 13.3%, presenteeism (impairment while working) at 17.7%, and overall work productivity loss at 17.7% due to IgAN-related reasons (only 3 FSGS patients [33.3%] were employed; outcomes not shown). Mean percent activity impairment was reported at 27.3% in IgAN and 43.3% in FSGS patients. Most paired care-partners were partners of patients (IgAN: 81.8%, FSGS: 71.4%), with a mean age of 46.6 years (IgAN) and 50.1 years (FSGS). Mean (SD) SF-12 PCS and MCS of IgAN care-partners were 53.3 (8.8) and 47.9 (10.8), respectively (FSGS: 47.0 [10.6], 49.4 [9.5]). Mild to moderate anxiety was reported in 31.8% (IgAN) and 42.9% (FSGS) of care-partners, with one IgAN care-partner (4.6%) reporting severe anxiety. Mild to moderate depression was reported in 27.3% (IgAN) and 71.4% (FSGS) of care-partners, with two IgAN care-partners (9.1%) reporting moderately severe or severe depression. Among employed IgAN care-partners (86.4%), mean percent absenteeism was reported at 14.2%, presenteeism at 9.3%, and overall work productivity loss at 9.9% due to IgAN-related reasons. Mean percent activity impairment was reported at 18.6% in IgAN and 17.1% in FSGS care-partners. Conclusion Patients with IgAN and FSGS in Europe experience impaired HRQoL compared to previously published European population estimates, as well as anxiety, depression, and impaired productivity. Care-partners of these patients also experience impaired HRQoL, in terms of mental components, and reduced overall productivity.

#190 Long-term treatment with lumasiran: final results from the phase 2 open-label extension study

Abstract Background and Aims Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder in which hepatic oxalate overproduction can lead to kidney failure and life-threatening systemic disease. Lumasiran, an RNA interference (RNAi) therapeutic indicated for treatment of PH1 to lower urinary oxalate (UOx) and plasma oxalate (POx) levels, reduces hepatic oxalate production by degrading the mRNA encoding glycolate oxidase. Patients with PH1 who completed a Phase 1/2 study were eligible to enroll in a Phase 2 open-label extension (OLE) study (NCT03350451) within 12 months of completing the Phase 1/2 study. Method Patients enrolled in the 54-month Phase 2 OLE had previously met eligibility criteria for the Phase 1/2 study, including: age 6 to 64 years, PH1 confirmed by genetic criteria, 24-hour (24 h) UOx excretion &amp;gt;0.7 mmol/1.73 m2/day, estimated glomerular filtration rate (eGFR) &amp;gt;45 mL/min/1.73 m2, and a stable pyridoxine (vitamin B6) regimen for patients taking vitamin B6. In the Phase 2 OLE, patients were to initiate subcutaneous lumasiran 1.0 mg/kg once monthly (qM), 3.0 mg/kg qM, or 3.0 mg/kg every 3 months (q3M) based on their dose/regimen in the Phase 1/2 study. The primary endpoint was the incidence of adverse events (AEs). Secondary endpoints were change in 24 h UOx corrected for body surface area (BSA) over time, change in 24 h UOx:creatinine ratio (UOx:Cr) over time, and change in estimated glomerular filtration rate (eGFR) over time. Change over time in POx and plasma glycolate, incidence of anti-drug antibodies (ADAs), and rates of kidney stone AEs were also assessed. Results All 20 patients (median age 11.5 years; 65% female) who completed the Phase 1/2 study entered the Phase 2 OLE (Table 1). Most patients (65%) were taking vitamin B6 at baseline. All patients transitioned to the 3.0 mg/kg q3M dose/regimen by month (M) 21, and all patients completed the study. Six patients transitioned to commercially available lumasiran prior to M54 but on or after M45. The most common treatment-related AEs were injection-site reactions (ISRs) with 13 events in 8 patients (40%); all ISRs were graded mild. Of all lumasiran doses administered during the OLE, 3% (13 of 427 total doses of lumasiran) were associated with ISRs. Other than ISRs, the only treatment-related AEs affecting &amp;gt;1 patient were increases in bilirubin (N=3 patients; 15%); all events resolved without lumasiran dosing changes. Severe AEs were reported by 2 patients (10%); serious AEs were reported by 7 patients (35%). No deaths occurred. No severe or serious AEs were related to treatment, and no patients discontinued lumasiran or withdrew due to AEs. Lumasiran treatment led to a substantial reduction in 24 h UOx relative to the Phase 1/2 study-derived baseline (Fig. 1A). At M54, the mean absolute change from baseline in 24 h UOx was −1.5 mmol/24 h/1.73 m2 and the mean percent change was −68%. From M42 through M54, 24 h UOx was ≤1.5×ULN in ≥89% of patients. At M54, the mean percent change from baseline in 24 h UOx:Cr was −77%. Mean eGFR was generally stable over time (Fig. 1B). Mean absolute change from baseline in eGFR at M54 was −1.6 mL/min/1.73 m2. Lumasiran treatment also led to reductions in POx from baseline, and mean post-baseline POx values remained within the normal range through M54. Mean plasma glycolate levels were elevated at the start of the Phase 2 OLE due to persistence of the treatment effect from the Phase 1/2 study. After treatment resumed, levels increased and then plateaued. One patient (5%) had an ADA positive result at M6 but no ADA-related AEs; subsequent tests were negative through M48. Overall, the kidney stone AE rate was low during the Phase 2 OLE (0.17/person-year (PY]); by comparison, the rate of symptomatic kidney stones was 0.45/PY during the 12 months prior to the Phase 1/2 study and the kidney stone AE rate was 0.90/PY during the Phase 1/2 study. Conclusion In the longest follow-up reported to date, lumasiran treatment was well tolerated in patients with PH1 in the Phase 2 OLE. The most common treatment-related AEs were mild, transient ISRs; no severe or serious AEs were treatment related. Mean 24 h UOx reductions were sustained over more than 4.5 years of treatment. Mean eGFR was stable over time.

#1891 Evaluating the safety and effectiveness of Tolvaptan for management of adult Korean ADPKD patients (ESSENTIAL study): final report

Abstract Background and Aims Tolvaptan, a selective vasopressin V2 receptor antagonist, was first approved by Korean FDA in 2015 as a treatment option in autosomal dominant polycystic kidney disease (ADPKD). In order to prescribe Tolvaptan safely and effectively, we designed the phase 4 clinical trial among Korean ADPKD patients with chronic kidney disease (CKD) stage 1-3. Method Korean patients aged 19 to 50 with rapidly progressing ADPKD were enrolled in the study. The dose titration was performed every one week for a total of 4 weeks. The patient was prescribed Tolvaptan with the maximum tolerable dose up to 120 mg per day. A total duration of Tolvaptan prescription was 24 months. The primary outcome was the incidence of treatment emergent adverse events (TEAE) including drug-induced liver injury (DILI). The secondary outcomes were the annual mean percent change of total kidney volume (TKV) and the annual mean change of estimated glomerular filtration rate (eGFR). Results A total of 117 patients were included in the analysis. Mean age was 38.7 ± 8.4 years old and male were predominant (58.1%). The average TKV was 2066 ± 1094 mL and mean eGFR was 79.7 ± 27.7 mL/min/1.73 m2. Mean duration of Tolvaptan exposure was 1.7 ± 0.6 years and the average daily dose of Tolvaptan was 94.4 ± 24.1 mg/day. A total of 489 treatment-emergent adverse events (TEAE) occurred in 106 (90.6%) patients during study duration. The drug-induced liver injury and aquaresis-related adverse events were two most common adverse events. A total of 17 DILI cases (14.5%) occurred during the study period and mostly within 18-month period. However, liver enzymes were normalized after drug discontinuation The patients with previous history of liver disease as well as those who were prescribed higher dose of Tolvaptan demonstrated higher frequency of DILI. Mean growth rate of TKV after Tolvaptan treatment was 4.5 ± 0.5% and mean eGFR decline rate was -3.0 ± 0.39 mL/min/1.73 m2/year. Comparing with the predicted value from calculation, Tolvaptan attenuated both TKV growth and eGFR decline rate. Conclusion This study is the first post-marketing survey assessing the safety and efficacy of Tolvaptan in Korean ADPKD patients. The incidence of DILI was higher than the previous studies and especially in those with liver disease and higher Tolvaptan prescription dose. While Tolvaptan can effectively reduce TKV and attenuate eGFR decline, the clinicians should be aware of higher frequency of DILI among Korean population.

Organ-specific mercury stable isotopes, speciation and particle measurements reveal methylmercury detoxification processes in Atlantic Bluefin Tuna

Identifying metabolism and detoxification mechanisms of Hg in biota has important implications for biomonitoring, ecotoxicology, and food safety. Compared to marine mammals and waterbirds, detoxification of MeHg in fish is understudied. Here, we investigated Hg detoxification in Atlantic bluefin tuna Thunnus thynnus using organ-specific Hg and Se speciation data, stable Hg isotope signatures, and Hg and Se particle measurements in multiple tissues. Our results provide evidence for in vivo demethylation and biomineralization of HgSe particles, particularly in spleen and kidney. We observed a maximum range of 1.83‰ for δ202Hg between spleen and lean muscle, whereas Δ199Hg values were similar across all tissues. Mean percent methylmercury ranged from 8% in spleen to 90% in lean muscle. The particulate masses of Hg and Se were higher in spleen and kidney (Hg: 61% and 59%, Se: 12% and 6%, respectively) compared to muscle (Hg: 2%, Se: 0.05%). Our data supports the hypothesis of an organ-specific, two-step detoxification of methylmercury in wild marine fish, consisting of demethylation and biomineralization, like reported for waterbirds. While mass dependent fractionation signatures were highly organ specific, stable mass independent fractionation signatures across all tissues make them potential candidates for source apportionment studies of Hg using ABFT.

Assessment of CXCL13 plasma level in chronic lymphocytic leukemia and its relation to other prognostic markers

Abstract: BACKGROUND: Chronic lymphocytic leukemia is a mature B-cell malignancy where there is a progressive accumulation of leukemic cells with a distinctive immunophenotype as consequence to defective apoptosis and survival signals derived from the microenvironment. CXC chemokine ligand 13 (CXCL13) chemokines have recently emerged as crucial orchestrators for lymphocyte trafficking and activation. These secreted polypeptides exert their function by binding to specific cell surface receptors and can be divided into two categories: homeostatic and inflammatory. The CXCL13 is an efficacious attractant of naive B-cells in vitro and has been shown to be produced constitutively by stromal cells in lymphoid follicles of human lymph nodes. The CXCL13-CXCR5 axis has been previously shown to contribute to the progression of several malignancies and possibly CLL relapse. OBJECTIVE: The aim of this study to compare the plasma level of CXCL13 in a patient with CLL with healthy normal control and to correlate the plasma level of CXCL13 to beta-2 microglobulin (β2 M) and other hematological parameters in CLL. PATIENTS, MATERIALS AND METHODS: This cross-sectional study was conducted on 50 CLL patients who were newly diagnosed. A total of 30 healthy individuals were included in this study as a control group. Measurement of plasma CXCL13 and beta-2 microglobulin levels was done by the enzyme-linked immunosorbent assay. RESULTS: Fifty CLL patients were studied and compared with thirty control group of healthy individuals. The mean level of CXCL13 was 67.48 pg/ml in CLL patients while it was 69.2 pg/ml in control, so it is statistically not significant (P = 0.363). The mean level of β2 M was 50.89 ug/ml in CLL patients while it was 50.59 ug/ml in control, so it is statistically not significant (P = 0.702). The percentage of stage A of CLL patients was 22.44%, stage B was18.36%, and stage C was 10.20%. The percentages of lymphadenopathy, splenomegaly, and hepatomegaly were 66%, 32%, and 16%, respectively. The mean of malignant cell percentage in stage A was 55.18%; in stage B, it was 69.28%; and in stage C, it was 81%, so it is statistically significant (P &lt; 0.001). CXCL13 shows no statistically significant between Cd38+ and CD38− and P value was 0.950. CONCLUSIONS: There was no correlation in level of CXCL13 between the CLL group and the control group. There was no correlation in level of CXCL13 and β2 M in the CLL group.

Abstract A005: Exploring liquid biopsy for the detection of bladder cancer: Unraveling RNA fusions

Abstract Introduction: This study delves into the promising realm of liquid biopsy for the non-invasive detection of bladder cancer. Leveraging urine as a valuable source, our investigation focuses on identifying RNA fusions associated with bladder cancer, with specific attention to ETV6-NTRK3 and PRCC-TFE3. The utilization of liquid biopsy offers a less invasive and more accessible approach to diagnosing bladder cancer, potentially revolutionizing the field of cancer diagnostics. These specific RNA fusions in urine samples may serve as reliable biomarkers for early detection and monitoring of bladder cancer. This research contributes to the ongoing efforts to enhance diagnostic methodologies to improve patient outcomes and streamline cancer management. Materials and Methods: Urine was collected from healthy male donors using UAS, a urine preservative from Novosanis, for improved urine preservation and stability. The urine samples with UAS were centrifuged at 16,000 xg for 10 min to obtain cf-urine. Three 20 mL aliquots of the precleared supernatant urine samples were spiked with an RNA fusion reference standard from Anchor Molecular containing ETV6-NTRK3 and PRCC-TFE3RNA at a concentration of 20ng/mL. All samples were extracted using the nRichDX Revolution Max20 cfTNA Isolation Kit. The eluants from the extracted samples were DNAse treated. The extracted cfTNAs profile was assessed on 4150 TapeStation System, Agilent, using RNA ScreenTape. Extracted nucleic acids from urine were evaluated using a RT-qPCR assay to quantify the number of copies of the fusion RNAs. Results: The Renal RNA fusions ETV6-NTRK3 and PRCC-TFE3RNA were successfully extracted using the nRichDX Revolution cfTNA Isolation Kit. TapeStation analysis demonstrated prominent 18S and 28S peaks, confirming the successful extraction of RNA from 20 mL urine samples. The mean percent recovery of the recovered RNA Fusion mutation was about 70% via RT-qPCR. Conclusion: Our findings indicate a recovery rate of approximately 70% for spiked RNA fusions in the urine samples. This research holds the promise of revolutionizing cancer diagnostics by introducing a method that is not only reliable but also convenient for early detection and monitoring. Identifying specific RNA fusions in urine samples as biomarkers is a significant step in enhancing diagnostic methodologies. As we contribute to these ongoing efforts, we aim to improve patient outcomes and streamline the management of bladder cancer through innovative and effective diagnostic approaches. Citation Format: Mayer Saidian, Jason Saenz, Carlos Hernandez, Lauren Lee, Andrew Dunnigan, Yabin Lu, Nafiseh Jafari. Exploring liquid biopsy for the detection of bladder cancer: Unraveling RNA fusions [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A005.

Studies on genetic variability parameters for seed yield and its component traits in mungbean [Vigna radiata (L.) Wilczek] germplasm under arid environment

Genetic variability is the most important factor for the success of any crop improvement program. Hence, the evaluation of germplasm has to be conducted as a preliminary step to study the extent of variability available in the germplasm and to identify suitable high-yielding genotypes that can be utilized in the crop improvement program. The present investigation was carried out to estimate genetic variability, heritability, and genetic advance for yield and yield contributing characters among seventy-nine diverse genotypes of mungbean for eleven quantitative traits. Significant differences were observed among genotypes for all eleven characters studied. The high degree of genetic variability along with high heritability and high genetic advance as percent of mean were recorded for seed yield per plant, number of pods per plant, harvest index, biological yield per plant, and plant height; which indicates that these characteristics were under the control of additive gene action and therefore, form the basis of selection for the mungbean improvement program.

Text Messages With Financial Incentives for Men With Obesity

Effective weight loss interventions are needed for men with obesity. To determine whether an intervention that combined text messaging with financial incentives attained significant weight loss at the 12-month follow-up compared with the control group and whether an intervention of text messaging alone attained significant weight loss at the 12-month follow-up compared with the control group. An assessor-blinded randomized clinical trial conducted in Belfast, Bristol, and Glasgow areas in the UK. A total of 585 men with body mass index (BMI) of 30 or more were enrolled between July 2021 and May 2022. Final follow-up occurred June 2023. Participants were randomly assigned to 12 months of behavioral focused text messages combined with financial incentives (n = 196), 12 months of behavioral focused text messages alone (n= 194), or a waiting list (control group; n= 195). The financial incentive consisted of a monetary reward that was lost if weight loss targets were not met. All participants received weight management information and a pedometer at baseline. The 2 primary comparisons were the 12-month comparison of within-participant weight change between the text messaging with financial incentive group and the control group and the comparison between the text messaging alone group and the control group (minimum clinically important difference, 3%). The P value defined for statistical significance was P < .025 for each comparison. Of the 585 men (mean [SD] age, 50.7 [13.3] years; mean weight, 118.5 [19.9] kg; mean BMI, 37.7 [5.7]; 525 [90%] White), 227 (39%) lived in postal code areas with lower socioeconomic status, and 426 (73%) completed the 12-month follow-up. At the 12-month follow-up, compared with the control group, the mean percent weight change was significantly greater in the text messaging with financial incentive group (mean difference, -3.2%; 97.5% CI, -4.6% to -1.9%; P < .001) but was not significantly greater in the text messaging alone group (mean difference, -1.4%; 97.5% CI, -2.9% to 0.0, P = .05). The mean (SD) weight changes were -5.7 (7.4) kg for the text messaging with financial incentives group, -3.0 (7.5) kg for the text messaging alone group, and -1.5 (6.6) kg for the control group. The 12-month mean (SD) percentage weight changes from baseline were -4.8% (6.1%) for the text messaging with financial incentives group, -2.7% (6.3%) for text messaging alone group, and -1.3% (5.5%) for the control group. Of 366 adverse events reported, the most common were infections (83 [23%]). Of the 23 serious adverse events (6.3%), 12 (52%) occurred in the text messaging with financial incentives group, 5 (22%) in the texts messaging alone group, and 6 (26%) in the control group. None were considered related to participating in a trial group. Among men with obesity, an intervention with text messaging with financial incentive significantly improved weight loss compared with a control group, whereas text messaging alone was not significantly better than the control condition. These findings support text messaging combined with financial incentives to attain weight loss in men with obesity. isrctn.org Identifier: ISRCTN91974895.

Differences in weight-loss outcomes among race-gender subgroups by behavioural intervention delivery mode: An analysis of the POWER trial.

Prior in-person behavioural intervention studies have documented differential weight loss between men and women and by race, with Black women receiving the least benefit. Remotely delivered interventions are now commonplace, but few studies have compared outcomes by race-gender groups and delivery modality. We conducted a secondary analysis of POWER, a randomized trial (NCT00783315) designed to determine the effectiveness of 2 active, lifestyle-based, weight loss interventions (remote vs. in-person) compared to a control group. Participants with obesity and at least one cardiovascular disease risk factor (N = 415) were recruited in the Baltimore, MD area. Data from 233 white and 170 Black individuals were used for this analysis. Following an intention-to-treat approach, we compared the mean percent weight loss at 24 months by race-gender subgroups using repeated-measures, mixed-effects models. Everyone lost weight in the active interventions however, weight loss differed by race and gender. white and Black men had similar results for both interventions (white: in-person (-7.6%) remote (-7.4%); Black: in-person (-4.7%) remote (-4.4%)). In contrast, white women lost more weight with the in-person intervention (in-person (-7.2%) compared to the remote (-4.4%)), whereas Black women lost less weight in the in-person group compared to the remote intervention at 24 months (-2.0% vs. -3.0%, respectively; p for interaction <.001). We found differences between the effectiveness of the 2 weight loss interventions-in-person or remote-in white and Black women at 24 months. Future studies should consider intervention modality when designing weight loss interventions for women.

A rapid monitoring protocol to estimate unharvested corn biomass in waterfowl impoundments

AbstractConservation planners use bioenergetic models to develop habitat objectives that satisfy energetic demands of waterfowl during nonbreeding periods. In turn, natural resource managers should estimate yield and availability of natural and cultivated waterfowl forage to monitor contributions to objectives and support adaptive resource management. Because bioenergetic models are particularly sensitive to unharvested flooded croplands, we developed a rapid methodology to estimate biomass of unharvested flooded corn (Zea mays) and tested our methodology in impounded corn fields planted and flooded in western Tennessee during autumn and winter of 2019–2021. We evaluated accuracy of our rapid assessment method and conducted simulations to assess variance‐bias trade‐offs relative to sample size. Rapid assessments lasted 20 min ± 10 minutes per field. Our rapid assessment method underestimated number of kernels per ear by 2.6% ± 0.5%. After adjusting for underestimation bias, corn biomass across all surveys was 5,500 kg/ha ± 250 kg/ha, which is similar yield to previous literature from waterfowl impoundment fields. Sampling 15 ears per field allowed field biomass to be estimated within acceptable accuracy (i.e., variance [SE] of mean percent error &lt;1.8%). We recommend our rapid yield assessment method be incorporated into habitat monitoring protocols to efficiently and precisely estimate corn biomass for improved conservation planning initiatives. Additionally, our rapid assessment method allows managers to monitor field yield rapidly, enabling estimates of corn depletion and availability throughout the nonbreeding season for waterfowl to support management decisions.

Environmental phenol exposures in 6- to 12-week-old infants: The Infant Feeding and Early Development (IFED) study

BackgroundExposure to phenols, endocrine-disrupting chemicals used in personal care and consumer products, is widespread. Data on infant exposures are limited despite heightened sensitivity to endocrine disruption during this developmental period. We aimed to describe distributions and predictors of urinary phenol concentrations among U.S. infants ages 6–12 weeks. MethodsThe Infant Feeding and Early Development (IFED) study is a prospective cohort study of healthy term infants enrolled during 2010–2013 in the Philadelphia region. We measured concentrations of seven phenols in 352 urine samples collected during the 6- or 8- and/or 12-week study visits from 199 infants. We used linear mixed models to estimate associations of maternal, sociodemographic, infant, and sample characteristics with natural-log transformed, creatinine-standardized phenol concentrations and present results as mean percent change from the reference level. ResultsMedian concentrations (μg/L) were 311 for methylparaben, 10.3 for propylparaben, 3.6 for benzophenone-3, 2.1 for triclosan, 1.0 for 2,5-dichlorophenol, 0.7 for BPA, and 0.3 for 2,4-dichlorophenol. Geometric mean methylparaben concentrations were approximately 10 times higher than published estimates for U.S. children ages 3–5 and 6–11 years, while propylparaben concentrations were 3–4 times higher. Infants of Black mothers had higher concentrations of BPA (83%), methylparaben (121%), propylparaben (218%), and 2,5-dichorophenol (287%) and lower concentrations of benzophenone-3 (−77%) and triclosan (−53%) than infants of White mothers. Triclosan concentrations were higher in breastfed infants (176%) and lower in infants whose mothers had a high school education or less (−62%). Phenol concentrations were generally higher in summer samples. ConclusionsWidespread exposure to select environmental phenols among this cohort of healthy U.S. infants, including much higher paraben concentrations compared to those reported for U.S. children, supports the importance of expanding population-based biomonitoring programs to infants and toddlers. Future investigation of exposure sources is warranted to identify opportunities to minimize exposures during these sensitive periods of development.

Development and testing of two tools to assess point-of-sale food and beverage marketing to children in restaurants.

To describe the development and testing of two assessment tools designed to assess exterior (including drive-thru) and interior food and beverage marketing in restaurants with a focus on marketing to children and teens. A scoping review on restaurant marketing to children was undertaken, followed by expert and government consultations to produce a draft assessment tool. The draft tool was mounted online, and further refined into two separate tools: the Canadian Marketing Assessment Tool for Restaurants (CMAT-R) and the CMAT-Photo Coding Tool (CMAT-PCT). The tools were tested to assess inter-rater reliability using Cohen's Kappa and percent agreement for dichotomous variables, and intra-class correlation coefficients for continuous or rank order variables. Waterloo, Ontario, Canada. Restaurants of all types were assessed using the CMAT-R (n = 57), and 30 randomly selected photos were coded using the CMAT-PCT. The CMAT-R collected data on general promotions and restaurant features, drive-thru features, the children's menu, and the dollar/value menu. The CMAT-PCT collected data on advertisement features, features considered appealing to children and teens, characters. The inter-rater reliability of the CMAT-R tool was strong (mean percent agreement was 92.4%, mean Cohen's κ = 0.82 for all dichotomous variables and mean ICC = 0.961 for continuous/count variables). Mean percent agreement for the CMAT-PCT across items was 97.3%, and mean Cohen's κ across items was 0.91, indicating very strong inter-rater reliability. The tools assess restaurant food and beverage marketing. Both showed high inter-rater reliability and can be adapted to better suit other contexts.

Estimation of population mean using ranked set sampling in the presence of measurement errors

Ranked set sampling is widely acknowledged for its superior efficiency compared with simple random sampling. Only a small amount of work has been conducted using ranked set sampling when measurement errors are present. This study introduces innovative estimators utilizing ranked set sampling to assess the population mean when faced with both correlated and uncorrelated measurement errors. The expressions for the bias and mean squared error of the proposed estimators are derived up to the first-order approximation, revealing their superior performance compared to the other examined estimators. The efficacy of the suggested estimators in handling measurement errors was demonstrated through numerical illustration and simulation study investigations. The recommended estimators are further compared to the existing ones using the percentage relative efficiency and mean squared error, and the impact of measurement errors on the results is highlighted through the percentage computation of measurement errors. The innovative estimators suggested were formulated by judiciously incorporating ratio, exponential, and log estimators. Numerical examples involving expenditure and income, as well as simulated data generated from a normal population using R software, affirm the superior performance of the proposed estimators over existing ones such as the usual mean estimator and those proposed by Vishwakarma and Singh (2022), as evidenced by the higher percent relative efficiency and lower mean squared error. The evaluation of the percentage contribution of measurement error values confirms the impact of measurement errors on the properties of the estimators.