High Load Research Articles

Musculoskeletal Disorders in COVID-19 Surveillance Staff Members: An Analysis of Prevalence, Risk Factors, and Coping Strategies

Aims/Background During the coronavirus disease 2019 (COVID-19) pandemic, the COVID-19 surveillance staff members experienced an increased risk for musculoskeletal disorders. Thus, it is necessary to further investigate the causal factors stemming from COVID-19 surveillance work, especially nucleic acid testing, and establish their relationship with work-related musculoskeletal disorders (WMSDs) by building upon the previous research. This study aimed to determine the prevalence of WMSDs and the major risks faced by the COVID-19 surveillance staff members. Methods This cross-sectional study was conducted in May 2022. The Quick Exposure Check (QEC), Nordic Musculoskeletal Questionnaire (NMQ), and Maslach Burnout Inventory (MBI) were used to evaluate ergonomic factors, musculoskeletal symptoms and pressure among 131 COVID-19 surveillance staff members in four hospitals in South-central Henan Province. Additionally, data regarding the coping strategies adopted by the respondents for lowing the risk of developing WMSDs were collected using a self-report questionnaire. Results The QEC results showed that the back, neck, and should/arm of the COVID-19 surveillance staff members bore high ergonomic loads, while the wrist suffered a medium load. The neck (75.6%), shoulder (66.4%), upper back (58%), and wrist (55.7%) were at higher risk for musculoskeletal disorder. Most of the respondents claimed a low sense of achievement (124, 94.7%) and slightly less than half of them had endured emotional exhaustion at work (61, 46.6%). Prolonged period of maintaining the same posture at work, awkward bending or twisting of back side, task repetition and so on were the perceived job risk factors precipitating WMSDs among the participants in this study. The top three coping strategies for lowering the risk of WMSDs included adjusting the plinth/bed height (49.6%), utilizing different parts of the body at work (47.3%), and taking short breaks when required (33.6%). Conclusion Prolonged large-scale nucleic acid detection can aggravate the musculoskeletal injuries of the neck, shoulder, upper back, and wrist in COVID-19 surveillance staff members. Prevention measures for musculoskeletal injuries factors must be in place to deter such incidence at work.

Horodynamic Mapping of Open Sands in the East of the Stavropol Region

The desertification processes that are dynamically occurring in the north-east of the Stavropol Territory are closely interrelated with climatic conditions, which necessitates the rapid mapping of qualitative changes in the state of open sands in accordance with various scenarios. The mapping was carried out on the basis of the technique of chorodynamic (diachronic) mapping for two periods (July-August 2022 and June-July 2023), data on the monthly dynamics of open sand areas, precipitation and dust storms were used to select time slices. The mapping was carried out visually on the basis of multispectral satellite images of Landsat for each month. In 2022, 14 dust storms were registered, in 2023 none were registered, and days with critical wind speeds were accompanied by heavy precipitation, in connection with which a significant decrease in the visible areas of open sands was revealed as a result of overgrowth. Based on the available data, using overlay operations, schemes of qualitative transitions in the test area (part of the Levokumsky district) corresponding to qualitative transitions in the “dry” and “wet” scenarios were compiled. Despite the progressive overgrowth of the sands, stimulated by the absence of dust storms and abundant precipitation in 2023, starting from areas with the lowest sediment capacity, the restoration of the original plant communities without carrying out phytomeliorative measures is extremely unlikely due to high anthropogenic load and seed desertification, as a result of which low-value annual crops grow on open sands (weed solyanka, kumarchik, nightshade horned, etc.).

A MXene Modulator Enabled High‐Loading Iodine Composite Cathode for Stable and High‐Energy‐Density Zn‐I2 Battery

AbstractAchieving both high iodine loading cathode and high Zn anode depth of discharge (DOD) is pivotal to unlocking the full potential of energy‐dense Zn‐I2 batteries. However, this combination exacerbates the detrimental shuttle effect of polyiodide intermediates, significantly impairing the battery's reversibility and stability. Herein, this study reports an advanced high‐loading iodine cathode (denoted as MX‐AB@I) enabled by a multifunctional Ti3C2Tx MXene modulator, which presents high stability and energy density in Zn‐I2 batteries. Through comprehensive experimental and theoretical analyses, the intrinsic regulating mechanisms are elucidated by which the MXene modulator effectively suppresses polyiodide shuttling, enhances iodine conversion kinetics, and dramatically improves Zn anode reversibility. With the aid of the MXene modulator, the MX‐AB@I composite cathode achieves a high iodine mass loading of 23 mg cm−2 and realizes a practically high areal capacity of 4.0 mAh cm−2. When paired with a thin Zn anode (10 µm), this configuration realizes a high Zn DOD of 78.7% and a high energy density of 171.3 Wh kg−1, surpassing the majority of Zn‐I2 battery systems reported in the literature. This study presents an effective approach to designing high‐loading iodine cathodes for Zn‐I2 batteries by leveraging MXene modulators to regulate critical electrochemical reaction processes.

Engineering Triple-Phase Interfaces with Hierarchical Carbon Nanocages for High-Areal-Capacity All-Solid-State Li-S Batteries.

All-solid-state lithium-sulfur batteries (ASSLSBs) have garnered widespread attention due to their advantages of high energy density and enhanced safety. However, the typical composite structure composed of solid-state electrolyte (SE), discrete conducting carbon black, and microsized sulfur (μ-S) with long-range Li+/e- conducting path and huge volume changes, suffers from sluggish charge transport and severe electrochemical-mechanical failure. In this work, a unique hierarchical carbon nanocage (hCNC) is applied as a continuous conducting network where nanosized sulfur are confined. Due to the synergistic effects of multi-dimensional (particle, interface, and electrode) structural engineering, this new sulfur-carbon composite cathode (S@hCNC39) can achieve uniform distribution of sulfur and carbon, and efficiently constructs triple-phase interfaces, showing enhanced charge-carrier transport and improved electrochemical-mechanical stability. Remarkable cycling performance of 89% after 300 cycles at 0.2C at 30°C is realized in ASSLSBs assembled with S@hCNC39. Notably, ASSLSBs achieve an ultrahigh areal capacity of 9.95 mAh cm-2 with stable cycling at 60°C with high sulfur contents of 40% and high sulfur loadings of 6mg cm-2. These results provide critical insights into the design of rational sulfur-carbon composites and offer a viable approach to enhance the overall performance of ASSLSBs.

Anatase‐reinforced PtZn@Silicalite‐1 structured catalysts boosting propane dehydrogenation

AbstractStructured catalysts exhibit the advantages of high diffusion efficiency and low heat transfer resistance, which have attracted increasing attention to non‐adiabatic gas–solid process. However, the metal‐supported coating catalysts face the problems of weaker bond strength and severe sintering, especially under the conditions of large flow rate and high temperature. Herein, metal@Silicalite‐1 structured catalysts with high adhesion and thermal stability were successfully prepared by hydroxylating the substrate with anatase. Rich surface Ti‐OH significantly strengthened the adhesion stability of the zeolite coating. In propane dehydrogenation reaction, the optimized PtZn@S‐1‐15Ti showed a high specific activity of 49.6 molC3H6·molPt−1·s−1 with propylene selectivity above 99% at 600°C. The introduction of anatase accelerated the aggregation of silicon sources and induced nucleation with growth content of zeolite increased by 3.6 times. It breaks the inherent contradiction between high loading amount and strong binding ability of coated catalysts, which broadens the avenues for industrial applications.

Factors associated with High Viral Loads among HIV Patients Under ARV at Gitwe District Hospital

Background: High viral load is a condition of rapid multiplication in blood stream. The high viral load among HIV patients under ARV may also occur due to the rapid multiplication of virus leading to compromise immune system of living organism up to death. The vast majority of people living with HIV virus face with persistent of high viral load while were under treatments (ARV). Aim: The aim of the study was to evaluate and assess the factors associated with high viral load among HIV patients under ARV at Gitwe District Hospital. Methodology: The retrospective study was conducted to assess high viral load of HIV patients under ARV. The only significance factor for viral load were adherence with (p=0.000173) and ages with (p=0.00023). Results and conclusion: A large of number of PLWH were highly VL tested, and 95 subjects were recorded for study. Among 95 subjects, 54.73% were female and 45.26% male. All data were analyzed using statistical package for social science (SPSS) version 20. The results have showed provider’s advices and ART use, adherence counselling. Keywords: High viral load, HIV, Antiretroviral therapy, Gitwe District Hospital.

Six weeks of polarized functional interval training with large training load reductions does not affect performance gains compared to traditional workouts

PurposeHigh-intensity functional interval training (HIFT) is predominantly composed of high exercise training intensities (HiT) and loads. Both have been linked to a higher risk of overtraining and injuries in inexperienced populations. A polarized training approach is characterized by high amounts of low-intensity training (LiT) and only approximately 5%–20% HiT. Compared to HIT-based training, this approach can result in temporary training load and intensity reductions without diminishing training gains. Thus, we aimed to examine the effects of traditional (TRAD) HIFT vs. polarized (POL) HIFT on relevant performance parameters.MethodsThirty athletes (15 females, age: 26.6 ± 5.0 years, height: 1.76 ± 0.13 m, body mass: 79.6 ± 12.4 kg, prior experience: 2.3 ± 2.0 years, training volume: 6.1 ± 2.4 h/wk) were randomly assigned to 6 weeks of either POL (78% LiT, 22% threshold intensity training (ThT) to HiT) or TRAD (26% LiT, 74% ThT to HiT). HIFT performance testing focused on maximal strength (squat: SQ1RM, deadlift: DL1RM, overhead press: OHP1RM, high pull: HP1RM), endurance (peak oxygen uptake: V̇O2peak, lactate threshold: LT, peak power output (PPO), and benchmark HIFT workout (Jackie: 1000 m rowing, 50 thrusters, and 30 pull-ups for time).ResultsPOL (785 ± 71 au) completed significantly (p ≤ 0.001; SMD = 4.55) lower training load (eTRIMP) than TRAD (1,273 ± 126 au). rANCOVA revealed no statistical relevant group×time interaction effects (0.094 ≤ p ≤ 0.986; 0.00 ≤ ηp2 ≤ 0.09) for SQ1RM, DL1RM, OHP1RM, high pull, V̇O2peak, LT, PPO, and Jackie performance. Both groups revealed trivial to moderate but significant (rANCOVA time effects: p ≤ 0.02; 0.01 ≤ ηp2 ≤ 0.11; 0.00 ≤ SMD ≤ 0.65) performance gains regarding DL1RM, OHP1RM, HP1RM, and Jackie.ConclusionDespite a notably lower total training load, conditioning gains were not affected by a polarized functional interval training regimen.

Ionic Liquid Additive Mitigating Lithium Loss and Aluminum Corrosion for High-Voltage Anode-Free Lithium Metal Batteries.

Concentrated electrolytes based on lithium bis(fluorosulfonyl)imide (LiFSI) have been proposed as an effective Li-compatible electrolyte for anode-free lithium metal batteries (AFLMBs). However, these electrolytes suffer from severe aluminum corrosion at an elevated potential. To address this issue, we propose a binary ionic liquid (IL) electrolyte additive comprising the 1-methyl-1-butyl pyrrolidinium cation (Pyr14+), difluoro(oxalate)borate anion (DFOB-), and difluorophosphate (PO2F2-) anion to mitigate the Li inventory loss and Al corrosion in 4 M LiFSI/DME electrolyte simultaneously. On the anode side, the IL additive facilitates the formation of a robust Li3N- and LiF-rich solid electrolyte interphase, promoting highly reversible Li plating/stripping and uniform Li deposition. Additionally, the ILs alter the Li+ solvation structure, leading to enhanced tLi+ and rapid Li+ desolvation kinetics. Concurrently, on the cathode side, the ILs aid in the generation of dense LiF- and AlF-rich passivation films against Al corrosion. By using the IL-added electrolyte, the Cu||LiMn0.7Fe0.3PO4 cell operates stably at 4.5 V, and the Cu||NCM613 cell with a high loading of 4.0 mA h cm-2 sustains 142 cycles until 80% capacity retention. This research contributes to a deeper understanding of the IL additive mechanism at the electrode-electrolyte interfaces and offers a straightforward approach to designing practical high-voltage AFLMB electrolytes.

Porphyrin-Camptothecin (CPT) Grafted Polyoxazoline Amphiphiles for Tumor Photodynamic-Chemotherapy Combination Treatment.

Porphyrin-based photosensitizers are extensively utilized in the realm of photodynamic therapy, capitalizing on their advantageous optical, chemical, and electronic properties. Nonetheless, their application is often constrained by their pronounced hydrophobicity. Structures with a high load capacity and excellent biocompatibility are preferred options to circumvent this obstacle. Herein, we constructed a novel porphyrin-camptothecin (CPT) polymer, which is composed of amphiphilic oxazoline segments, and the drug monomers containing disulfide bonds are modified on the hydrophobic chain of polyoxazoline. The polyoxazoline-porphyrin-CPT (OPC) polymer can self-assemble into nanoparticles in the aqueous phase, possesses excellent stability, and generates abundant singlet oxygen (1O2) under laser irradiation. Additionally, the OPC nanoparticles exhibit satisfactory biocompatibility and high light toxicity against 4T1 cells. In the microenvironment of the tumor, drugs were released from the OPC nanoparticles owing to the high concentration of GSH, causing direct damage to the tumor cell, achieving the combination of photo-chemotherapy. The findings of this research indicate that polyoxazoline porphyrin demonstrates adaptability as a nanoplatform for cancer treatment.

Determinant Factors of Microbial Drinking Water Quality at the Point of Use in Rural Ethiopia: A Case Study of the South Gondar Zone

Access to safe drinking water is a fundamental human need for health and well-being implemented globally by the United Nations under Sustainable Development Goal (SDG) 6. Storing drinking water is common in rural areas of Ethiopia due to off-premises water sources and intermittent piped water supply. However, this practice can lead to further contamination during collection, transport, and storage, posing a risk to public health. The objective of this study was to identify the determinant factors of drinking water quality at the point of use in the rural setting of northwestern Ethiopia, South Gondar zone. A questionnaire survey was conducted, and water samples from 720 households were collected during the wet and dry seasons. The determinant factors were identified using the multivariable logistic regression model. About 39.2% of the surveyed households had basic water supply services, 41.9% were using unimproved sources, and 8.3% were using surface water. Only 9.4% were using basic sanitation services, and 57.2% were practicing open defecation. Safe water storage was practiced by 84.3% of households, while only 2% engaged in household water treatment. About 14% of dry and 8% of wet season samples from the storage were free from fecal coliform bacteria. Furthermore, 52.9% of dry and 62.2% of wet season samples fell under the high microbial health risk category. The season of the year, the water source type, storage washing methods, and the socioeconomic status of the household were identified as key predictors of household drinking water fecal contamination using the multivariable logistic regression model. It was observed that the drinking water in households had a high load of fecal contamination, posing health risks to consumers. To tackle these problems, our study recommends that stakeholders should enhance access to improved water sources, implement source-level water treatment, increase access to improved sanitation facilities, advocate for safe household water management practices, and endorse household water treatment methods.

In vitro analysis of flowable and high viscosity bulk fill composite versus conventional composite in core build up of endodontically treated teeth.

This study aimed to test the load to fracture of flowable and high viscosity bulk-fill composites compared to a convetional (packable) composite used to build up pulpless teeth. 45 endodontically treated premolars were restored with fiber posts then divided into three groups (N = 15) according to the core build-up material. SDR group: (Smart Dentine Replacement), (BF): Filtek One Bulk Fill and (CC) Filtek Z350 packable composite. After core build up the teeth received full coverage crowns. Load to fracture (Newton) was recorded for each specimen. One-way ANOVA and Tukey multiple comparisons test were used. The highest load at fracture was shown by (CC) group (1067N), followed by (BF) group (879N), and the SDR group (838N). One way ANOVA and Tukey's multiple comparisons test demonstrated no significant differences between CC, SDR, and BF groups (p > 0.05). The three materials showed comparable load to fracture. Further studies with simulation to occlusal forces and oral temperature are required.

The possible link between venison poisoning and Sarcocystis spp. infection in Lithuania: a case report.

There have been report of possible food poisoning in Lithuania following the consumption of raw steaks from a roe deer (Capreolus capreolus). Two people experienced symptoms of abdominal pain, watery diarrhea, loss of appetite, and nausea. The parasitological examination of the roe deer revealed macrocysts of Sarcocystis sp. to the naked eye. Microscopic sarcocysts of Sarcocystis spp. were detected in different muscles, and a high sarcocyst load was observed in the roe deer muscles by a light microscope. Based on molecular results, S. capreolicanis, S. gracilis, S. linearis, S. oviformis, and S. silva were identified in meat samples of the roe deer. This is the first report of a possible link between venison poisoning and Sarcocystis spp. infection in Lithuania.

Phthalate esters in baltic lagoons: Spatial distribution, ecological risks, and novel insights into their fate using transcriptomics.

Plasticizers such as phthalate esters (PAEs) are organic compounds widely used in various consumer and industrial products, raising strong environmental concerns due to their pervasive presence and potential adverse effects. Lagoon ecosystems are particularly vulnerable to PAE pollution as they are semi-enclosed and receive high loads of organic materials. The present study investigates the distribution of seven common PAEs in three large European lagoons (Curonian, Vistula and Szczecin) in the southern Baltic Sea. The concentration levels of PAEs in the water column, encompassing both the dissolved and particulate-bound phases, and in sediments were assessed to elucidate distribution patterns and potential ecological risks within these lagoon ecosystems. The average concentration of total PAEs in the water column ranged from 0.03 to 1.45 μg L-1, whereas sediment concentration varied from 0.008 to 1.06 μg g-1, levels comparable to or lower than those found in other European coastal areas. Distribution patterns of PAEs in sediment showed notable similarity across all three lagoons, whereas variations were observed in the water column. Notably, di(2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DOP) and dimethyl phthalate (DMP) emerged as the most concerning congeners in studied lagoons, all of which pose a moderate risk to aquatic organisms. This study applied shotgun transcriptomic analysis to field samples, revealing active microbial communities involved in PAEs degradation in the Baltic lagoons for the first time. The degradation of phthalic acid (PA) into intermediate compounds such as protocatechuate was not identified as a rate-limiting step in the studied environment. The degradation activity was primarily localized in the sediment layers, with Gram-negative bacteria playing a major role, while Gram-positive bacteria appeared incapable of degrading PA. These findings provide valuable insights into the distribution and transformation mechanisms of PAEs in estuarine environments.

Riddelline from Tamarix articulate as a potential anti-bacterial lead compound for novel antibiotics discovery: A comprehensive computational and toxicological studies.

Tamarix articulate from the Tamaricaece family is a halophytic plant. This plant is commonly called Athal or Tamarix in different Arabic and Asian countries. Due to the high load of polyphenolic phytochemicals, the plant has been used as a therapeutic option against several diseases for decades. The plant is an anti-inflammatory, anti-bacterial, anti-viral, anti-cancer, anti-oxidant, and anti-inflammatory. In this work, the 222 phytochemical compounds of T. articulate from our previous study are used in different bioinformatic and biophysics techniques to explore their biological potency against different anti-bacterial, anti-cancer and anti-viral targets. By doing so, it was found that Riddelline ranked as the best binding molecule of biological macromolecules selected herein in particular the bacterial targets. The binding energy value of the compound for the KdsA enzyme was -14.64 kcal/mol, KdsB (-13.09 kcal/mol), MurC (-13.67 kcal/mol), MurD (-13.54 kcal/mol), MurF (-14.20 kcal/mol), Polo-like kinase 1 (Plk1) (-12.34 kcal/mol), Bcl-2 protein (-13.39 kcal/mol), SARS-CoV-2 main protease enzyme (-12.67 kcal/mol), and Human T cell leukemia virus protease (-13.67 kcal/mol). The mean Rg value of KdsA-Riddelline complex and KdsA-FPE complex is 32.67 Å, and average RMSD of KdsA-Riddelline complex and KdsA-FPE complex is 2.31 Å, respectively. The binding energy complexes was found to be dominated by van der Waals (-71.98 kcal/mol for KdsA-Riddelline complex and -65.09 kcal/mol for KdsA-FPE complex). The lead compound was also unveiled to show favorable druglike properties and pharmacokinetics. Together, the data suggest the good anti-bacterial activities of the T. articulate phytochemicals and thus can be subjected to experimental in vitro and in vivo investigations.

Effects of the Interaction Between Time-on-Task and Task Load on Response Lapses

To investigate the interaction effects of prolonged working periods and different task loads on response lapses, focusing on the mechanisms of delayed responses and error lapses. Professionals such as pilots, truck drivers, and nurses often face extended work hours and fluctuating task loads. While these factors individually affect performance, their interaction and its impact on response lapses remain unclear. Twenty participants completed the Uchida–Kraepelin (U–K) Psychological Test and a dual-task version with functional near-infrared spectroscopy. Independent variables were time-on-task and task load. Dependent variables included measures of fatigue, arousal, workload, task performance (delayed and error rates), and brain functional connectivity. Both time-on-task and task load significantly affected cerebral connectivity, response lapses, workload (frustration level), fatigue, and arousal. Arousal levels significantly decreased and reaction times increased after 60 min of work. Cognitive resource regulation became challenging after 90 min under high task load levels. A decline in the connection between the prefrontal and occipital cortex during high-load tasks was observed. The findings provide insight into the mechanisms of response lapses under different task load levels and can inform strategies to mitigate these lapses during extended work periods. This study’s findings can be applied to improve work schedules and fatigue management in industries like aviation, transportation, and healthcare, helping reduce response lapses and errors during extended work periods under high task load conditions.

Strain As An Indicator For Stress Fractures In Racehorses

Abstract The horse racing industry, despite its financial significance, grapples with significant welfare issues, particularly stress fractures in racehorses. Third metacarpal (MC3) bone fractures, constituting about one-third of all limb fractures, severely impact horse health and performance. The frequent occurrence of condylar fractures in the MC3, often resulting in bone comminution, poses high risks-sometimes necessitating euthanasia, and complicates the management and recovery processes for the rest. Comprehensive methods for quantitatively determining fracture risks in horses are lacking, with strain measurements on the MC3 during racing conditions showing promise as an indicator of high loads and potential fracture risks. This study investigated the mechanical properties of MC3 under high compressive loads. Six MC3 bones from euthanized horses were instrumented with strain gauge rosettes at four key locations: Lateral Condyle (CondL), Medial Condyle (CondM), Dorsal DistoLateral (DisL) and Dorsal DistoMedial (DisM). Each bone underwent a pre-loading phase and five cycles of 12kN sinusoidal loading to replicate galloping forces. Strain patterns were observed before and after introducing an artificial slot in the lateral condylar groove to simulate a fatigue crack. A strong correlation was found between load and minimum principal strain in both intact and fatigue crack-induced (FCI) bones, with R-squared values over 0.99. Post-FCI, 83% of bones exhibited an increase in the minimum principal strain-load response slope, indicating uniform changes in material behavior. Additionally, a rise in post-FCI y-intercept values across MC3 locations indicated higher initial strain and possible changes in bone properties.

Dynamic characteristics and transmission efficiency of energy-harvesting shock absorber with low speed and heavy duty capacity

Traditional hydraulic shock absorbers commonly encounter challenges such as cavitation, oil leakage, and the management of energy dissipation. The proposed regenerative shock absorber, which utilizes a ball screw mechanism, offers advantages such as high efficiency and heavy load capacity. This paper focuses on the design, modeling, and testing of a mechatronic shock absorber. Virtual prototype simulation techniques are employed to investigate the dynamic behaviors of the shock absorber. The paper presents a systematic efficiency model of a shock absorber, which is based on the ball screw and gearbox mechanisms. The study comprehensively analyzes the effects of rotation speed, axial load, and structure parameters on transmission efficiency. The results demonstrate that a peak power of 38 W can be achieved with a damping force of only 340 N, and the recovery efficiency can reach up to 28%. The experimental test results validate the effectiveness and reliability of the proposed dynamic and efficiency models. The originality of this study lies in the development of a novel energy-harvesting shock absorber with a ball screw mechanism in series with a gearbox, which shows excellent energy recovery potential and transmission efficiency under low speed and high duty conditions.

Bioinspired orthogonal-shaped protein-biometal nanocrystals enable oral protein absorption.

With the growing number of marketed biological drugs, the development of technological strategies for their oral systemic absorption, becomes increasingly important. The harsh gastrointestinal environment and low permeability of the intestinal epithelium, represent a huge challenge for their systemic delivery. Herein, bioinspired in the physiological insulin-Zn interaction, the design of orthogonal-shaped protein-biometal hybrid nanocrystals, further enveloped by a bilayer of functional biomaterials, is reported. The nanocrystals exhibited a size of 80 nm, a neutral surface charge and a high insulin loading. In vitro studies showed the capacity of the nanocomplexes to control the release of the associated insulin, while preserving its stability. In vivo evaluation showed sustained blood glucose reductions in both healthy and diabetic rats (up to 40 % and 80 %, respectively), while chronic immunotoxicity studies in mice indicated no toxicity effect. Preliminary efficacy studies in healthy awake pigs following oral capsule administration showed over 20 % absolute bioavailability.

Investigation of burnout effect in turbine blade tip leakage at transonic conditions – a numerical study

Abstract In the aviation industry, turbine blade tip leakage significantly impacts the economy due to aerodynamic losses in the turbine. The tip leakage flow increases when the tip surface is exposed to high heat loads from the burnout effect, contributing to nearly 30% of the total loss in the turbine stage. This study numerically investigates two-dimensional flat tip and burnt-out tip models under different flow accelerations at transonic conditions. Variations in the discharge coefficient are examined for different pressure ratios across the tip gap. Flow and shockwave patterns for various blade tip geometries are obtained and analyzed. The burnt-out tip notably increases tip leakage, and a significant decrease in turbine efficiency is observed beyond a critical burnout limit. The quantified losses at different stages of blade tip burnout are used to predict the effective operational life of the blade. A correlation is developed to relate the non-dimensional tip-leakage flow parameters to the normalized blade-tip geometry.

Abstract PR017: A T-cell signature in circulating cell-free DNA at time of diagnosis predicts response to checkpoint inhibition

Abstract Immune checkpoint inhibitors (ICI) are increasingly used as first line of treatment in a range of cancer types, owing to their efficacy and advantageous toxicological profile. Currently, PD-L1 expression and tumor mutation burden (TMB) are the most common biomarkers to select patients for ICI treatment, yet response to ICI remains highly variable between patients, necessitating more accurate early predictors of treatment response. Circulating cell-free DNA (cfDNA) originates from dying cells throughout the body, each molecule carrying unique epigenetic features of its cell-type of origin. Most studies on cfDNA focus on tumor-derived fragments for diagnostics or minimal residual disease detection. However, variations in the contribution of immune cells and other stromal cell populations could provide important clues to classify a tumor with respect to treatment. To address this, we collected tumor and adjacent normal tissue as well as cfDNA from the blood of 33 patients enrolled in the LUD2015-005 trial in which ICI were administered to patients with non-resectable esophageal adenocarcinoma (EAC) for four weeks, before adding standard-of-care chemotherapy (ICI+CTX). For each patient, we took samples at diagnosis, before ICI+CTX, during and at the end of treatment. Tissue and cfDNA samples were sequenced using TET-Assisted Pyridine-borane Sequencing (TAPS), a method recently developed in Oxford which provides genome-wide high-depth, base- resolution DNA methylation and mutation information from low-input samples. We then selected a representative set of high-purity tumor tissue samples and combined them with whole- genome TAPS data from 9 healthy blood cell types and 5 gastrointestinal tissues to generate a GI-specific atlas of cell-type specific methylation. This atlas allows us to accurately quantify the contribution of tumor and 14 healthy cell types to the cfDNA collected from each patient at each timepoint. Strikingly, the presence of T-cell derived cfDNA at time of diagnosis (tDNA) is a strong positive predictive marker of overall survival (p=0.0024). In contrast, the fraction of tumor-resident T-cells, estimated by either bulk tissue TAPS or RNA sequencing, correlated only weakly with treatment response in this cohort, indicating that T-cell activity is more accurately captured by tDNA. Furthermore, we find that patients with a combination of high TMB and high tDNA have an 80% 2-year survival probability, as opposed to below 25% for others, suggesting that tDNA is derived from T-cells actively engaging tumor cells with high neoantigen load. In summary, we demonstrate that T-cell turnover, as reflected in differential methylation in a set of marker regions spanning only 24kb, is a promising biomarker of treatment response, especially when combined with neoantigen load: in the presented cohort, all but one long-term survivors (alive at last follow up > 3 years after diagnosis) were tDNA positive with high TMB. This demonstrates the power of cfDNA composition analysis for risk stratification in ICI treatment. Citation Format: Phil Xie, Zohar Etzioni, Chun-Xiao Song, Richard P Owen, Mark R Middleton, Xin Lu, Benjamin Schuster-Boeckler. A T-cell signature in circulating cell-free DNA at time of diagnosis predicts response to checkpoint inhibition [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR017.