bluuebunny/crossref_metadata_2025 huggingface dataset:
Supercritical Carbon Dioxide Mixing Loss Characteristics Near the Critical Point
Authors: Wang Jinhong , Cao Teng , Martinez-Botas Ricardo
Published: September 2024

This paper aims to study the mixing loss characteristic of supercritical carbon dioxide (sCO2) near the critical point and shed light on the nonideal fluid effect on the mixing losses. As a simplified model of the mixing process in the trailing edge or tip leakage flow in turbomachines, a case of mixing in a constant area adiabatic duct involving two streams of parallel flows is studied by control volume analysis. Both perfect gas and nonideal fluid calculations are carried out for comparisons. The isolated and coupled effects of the two mixing streams' temperature, velocity, and pressure differences on the loss are investigated. The study shows that nonideal fluid mixing produces significantly higher losses when compared to the equivalent perfect gas estimation. It also reveals that the nonideal fluid mixing loss is sensitive to the average thermodynamic states of the mixing streams. A general trend is that the closer the temperature is to the critical point, the higher the loss is observed. This is particularly apparent for the temperature and pressure mixings, while the mixing loss due to the velocity difference is less affected. A significant variation of the mixing loss coefficient is reported if the static state of any of the two streams is near the critical point, which is mainly caused by the significant variation of the temperature gradient regarding the entropy along the isobar. In addition, a positive combined effect of the temperature, velocity, and pressure differences was found for mixing loss. The results also show that the change in the mixing loss due to the variation of one property difference between mixing streams is almost independent of the other property difference. This behavior matches the conclusion drawn in literature for perfect gases (Denton, J. D., 1993, “The 1993 IGTI Scholar Lecture: Loss Mechanisms in Turbomachines,” ASME J. Turbomach., 115(4), pp. 621–656). The results from this simple case contribute to understanding the mixing loss behavior differences between perfect gas and nonideal fluids in sCO2 turbomachinery and hold significance for the development of mean-line models.
Comparison of Ingestion of Different Size Hard and Soft Bodies Into a Representative Fan Assembly Model
Authors: Mattar Rashid E. , Sirivolu Dushyanth , D'Souza Kiran
Published: September 2024

Foreign matter ingestion into a jet engine is a significant hazard to the safety of aircraft. While soft body ingestions (i.e., bird or ice ingestions) have been extensively researched, the threat posed by uncrewed aircraft systems (UASs) is a more recent concern due to their recent rise in popularity and has not been thoroughly studied. To better understand the damage caused by UAS ingestions, it is crucial to examine the resulting ingestion damage in comparison to birds of similar mass. This analysis is an essential initial step in determining how previous knowledge regarding soft body ingestions can relate to this new threat. To properly analyze these ingestions, development of a model that accurately represents a fan assembly is essential. This model should include a fan, as well as representative boundary conditions for the ingestion, such as blade retention systems, nose cone, casing, and shaft. Items that are analyzed during the ingestion include the overall damage to the fan blades, average and peak forces imparted on the retention systems, impact loads with the casing, and transient loads due to impact on the shaft. The foreign object models used were experimentally validated at their nominal sizes to increase confidence in the results. Comparison of the effects of ingestion of UAS and birds of difference mass into the representative fan model are presented and discussed to gain a better understanding of the differences between soft and hard body ingestion.
Application of Interface Reduction Methods to Rotordynamic Casing Models
Authors: Paehr Martin , Panning-von Scheidt Lars
Published: September 2024

As the use of digital twins for the purpose of structural health monitoring increases, so does the demand for high-quality models. In the area of rotating machines, this means that the casing must also be taken into account. These are often geometrically complex assemblies that require the use of finite element models. The models are then reduced in size by established reduction methods like the Craig-Bampton reduction in order to keep the solution time, e.g. for a forced response analysis as low as possible. In case of nonlinear contact forces, e.g. friction in bolted joints, a secondary reduction step has to be applied. Here, three different interface reduction methods are investigated and used for a rotor-casing assembly including frictional damping. The necessary basics and terms are presented. The performance of the methods is evaluated for a linear model on substructure and assembly level and for a nonlinear model on the assembly level. The implementation of the interface reduction within the Harmonic Balance Method is presented and tested for different unbalance excitation cases.
Spray solution volumes to control Brevipalpus yothersi mite in successive applications and impact on citrus fruit drop with leprosis symptoms
Authors: Cardoso de Castro Matheus , Júnior de Andrade Daniel , Bassanezi Renato Beozzo , Franco Danilo , Fukuda Leandro Aparecido , Ferreira Marcelo Da Costa , De Andrade Daniel Júnior
Published: September 2024

Citrus leprosis mite [Brevipalpus yothersi Baker (Acari: Tenuipalpidae)] is traditionally controlled with acaricide applications using a high volume of spray solution (> 2000 L.ha-1). However, high spray solution volumes can generate water waste and environmental contamination. An experiment was set up in a sweet orange orchard located in the municipality of Taquaral, São Paulo, Brazil, aiming to optimize the spray solution volume required for more efficient control of the leprosis mite. The experiment was conducted from December 2020 to July 2022. Two spray solution volumes were evaluated: 100 and 180 mL m−3 of plant canopy. In total, seven acaricide applications were performed. During the experiment, we assessed the incidence and infestation of the leprosis mite. Additionally, at the end of the experiment, we counted the number of plants and fallen fruits exhibiting leprosis symptoms. The treatment with a spray volume of 180 mL m−3 was more effective in controlling mites, as the incidence and infestation of B. yothersi were lower in this treatment. Moreover, this treatment resulted in fewer plants with fallen fruits and a reduced number of fallen fruits showing leprosis symptoms.
Current–voltage characteristics of Ag/Nb:SrTiO3/Ag and Au/Nb:SrTiO3/Ag heterostructures
Authors: Bian Weibai , Han Chen , Jia Jiqiang , Liu Xiaoqin
Published: September 2024

Ag/Nb:SrTiO3(NSTO)/Ag and Au/NSTO/Ag structures were prepared and their current–voltage curves were studied in detail. The Ag/NSTO/Ag structure can demonstrate a pronounced resistive switching effect and the characteristics of its resistance change sequence as demonstrated in the I–V curves are significantly different from those of the Au/NSTO/Ag structure. Under a unipolar current, the Ag/NSTO/Ag structure translates first from a low-resistance state (LRS) to a high-resistance state (HRS) and then from the HRS to the LRS. However, the Au/NSTO/Ag structure only shows a transition from the HRS to the LRS. The phenomenon is analyzed taking into account the migration of oxygen ions and the electrochemical reaction of the Ag electrode, which lead to the formation of the Ag2O insulation layer as well as Ag conductive filaments in the Ag/NSTO/Ag structure and a change in the barrier height of the Au/NSTO interface.
Refraction/reflection reversal in two-dimensional acoustic metagratings
Authors: Zou Hong-yu , Qian Jiao , Xia Jianping , Gu Shuai , Lu Yu-jing , Ge Yong , Yuan Shou-qi , Chen Hongsheng , Sun Hong-xiang , Yang Yihao , Zhang Baile
Published: September 2024

Unlike acoustic metasurfaces that rely solely on phase gradients, acoustic metagratings (AMs) operate based on both phase gradients and grating diffraction, thus further extending the generalized Snell's law (GSL). In particular, AMs can achieve reversal of refraction and reflection based on the parity of the number of wave propagations inside the AMs. So far, discussions of this GSL extension have largely been applied to one-dimensional periodic AMs, while the designs of two-dimensional (2D) periodic AMs and their performance in three-dimensional (3D) space have been quite limited. Here, we study the GSL extension in 3D space and experimentally demonstrate a series of functional 2D periodic AMs. The designed AMs can achieve sound refraction/reflection under any incidence angle in 3D space, without restrictions to certain critical ranges; adjusting incident angles only enables the reversal of refraction and reflection. Additionally, we demonstrate two types of dual-layer sound lenses based on two AMs, whose reversal of refraction and reflection can be realized by simply attaching or separating the two AMs. Our work paves the way to complex 3D wavefront manipulation of AMs, which may find potential use in practical acoustic devices.
Whole-genome sequencing of
Mycobacterium tuberculosis
sublineage L1.1.1.7 from Chiangrai, Thailand
Authors: Nuttavuthisit Kanin , Ruangchai Wuthiwat , Bodharamik Thavin , Sawaengdee Waritta , Mahasirimongkol Surakameth , Palittapongarnpim Prasit
Published: September 2024

Mycobacterium tuberculosis
(MTB) presents a global health issue. Various genotypes of MTB have different geographic distributions. The majority of MTB in Thailand belong to lineages 1 and 2. Here, we report the complete genomic sequences of MTB sublineage L1.1.1.7, which is common in Thailand and infrequently identified in other countries.
Continental-scale insights into the sugarbeet diffusion juice microbiomes
Authors: Bill Malick , Eide John D. , Fugate Karen K. , Bolton Melvin D. , Kandel Hari P. , Kandel Shyam L.
Published: September 2024

Bacterial contamination of raw diffusion juice poses unique challenges during the sugar extraction process. This study profiled bacterial communities by using full-length 16S rRNA amplicon sequencing and quantified the carbohydrate concentrations in raw diffusion juice samples received from sugar factory regions across the USA and Canada. Juice samples were collected at four time points during the 2021 and 2022 processing campaigns.
Firmicutes
was the dominant phylum from the raw diffusion juice samples collected during both campaigns and comprised 85.5% of total bacterial abundance. Lactic acid bacteria such as
Leuconostoc
and
Lactobacillus
were among the core genera which also dominated the bacterial community in raw diffusion juice. Positive correlations in the abundance of functionally and taxonomically related bacterial communities were identified. During the 2021 campaign, 44 bacterial genera were differentially abundant in raw diffusion juice extracted from sugarbeet roots in Periods 1 to 4. This number declined sixfold during the 2022 campaign to three genera. The concentration of raffinose in raw diffusion juice positively correlated to the relative abundance of
Leuconostoc
. Furthermore, an
in vitro
assay was performed to assess the growth dynamics of
Leuconostoc mesenteroides
in sucrose or raffinose-rich medium and observed the rapid consumption of both carbohydrates by this bacterium. This finding is important for deciphering microbial growth dynamics in raw diffusion juice that can be useful in minimizing sugar loss during the factory processing.

IMPORTANCE

Findings additionally provide baseline information that can be used to develop mitigation strategies that reduce losses due to microbial contamination of sucrose processing streams.
Comparison of the indirect immunofluorescence assay and a commercial ELISA to detect KSHV antibodies
Authors: Leducq Valentin , Ben Said Léa , Sayon Sophie , Calvez Vincent , Marcelin Anne-Geneviève , Jary Aude
Published: September 2024

Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic virus involved in several diseases. The gold standard for KSHV sero diagnosis remains the indirect immunofluorescence assay (IFA), which is time-consuming and operator-dependent. We compared this method with an enzyme-linked immunosorbent assay (ELISA) targeting solubilized KSHV whole-genome extract among positive (
n
= 49, including 76% of HIV-infected patients) and negative (
n
= 14) control groups. We also included 14 sera with equivocal IFA results. ELISA showed better performance in detecting KSHV antibodies (McNemar’s test,
P =
0.0455). The sensitivity and specificity of both methods were 79% (64–89) and 100% (66–100) for the IFA, respectively, and 94% (83–99) and 100% (66–100) for ELISA, respectively. All IFA equivocal results were either negative or positive with ELISA. ELISA is more reliable and could be a good alternative for determining KSHV serological status, particularly in the context of immunocompromised patients and equivocal serology with the IFA.

IMPORTANCE

Kaposi’s sarcoma-associated herpesvirus (KSHV) sero status remains challenging because no perfect reference is available for the detection of KSHV antibodies. The current gold-standard method, the indirect immunofluorescence assay (IFA), has a very good specificity of close to 100%, but a lower sensitivity of around 80–85%, which decreases to 64–67% in immunocompromised patients. Additionally, this method is time-consuming and operator-dependent compared with new serological assays such as the enzyme-linked immunosorbent assay (ELISA). Thus, further research is still needed to improve KSHV sero diagnosis. Here, we compare the KSHV IgG ELISA kit assay (Advanced Biotechnologies Inc) with the gold-standard IFA, targeting the LANA-1 protein from latent BC-3 cell lines.
Scurvy—a re-emerging disease with the rising cost of living and number of bariatric surgical procedures
Authors: Dermawan Andrew , Eshon Sehrina , Danagher Kevin , Senaratne Sivanthi
Published: September 2024

This case presents a male in his early 50s with a bilateral painful petechial rash in the lower limbs, which occurred spontaneously without trauma. He also had macroscopic haematuria and macrocytic anaemia with mild neutropenia and lymphopenia. Vasculitis, autoimmune and haematological screens were negative. CT scan of his abdomen and lower limbs did not show any intra-abdominal bleeding or lower limb vasculitis. Skin biopsy was also unremarkable. His petechial rash continued to progress during admission. Further history revealed poor oral intake and cessation of his post-sleeve gastrectomy supplements due to financial constraints. A nutritional panel showed undetectable vitamin C levels, along with other nutritional deficiencies. He was diagnosed and treated for scurvy with ascorbic acid (vitamin C) 1000mg daily, and his painful rash and haematuria resolved.

Scurvy is a re-emerging disease with the rising cost of living. It can present as early as a month after a vitamin C-deficient diet. Petechial skin lesions often occur especially in the lower extremities and may be mistaken for systemic vasculitis. The diagnosis is often made after an extensive diagnostic workup including imaging and biopsies, thus delaying treatment. Risk factors for scurvy include poor nutrition, gastric bypass surgery, dialysis, alcoholism, psychiatric history and eating disorders. This disease is easily reversible with supplementation, with a dramatic response seen within 24 hours. Failure to treat may lead to catastrophic haemorrhage, hence, early recognition and prompt treatment are vital.
Value for money of medicine sampling and quality testing: evidence from Indonesia
Authors: Valente de Almeida Sara , Hauck Katharina , Njenga Sarah , Nugrahani Yunita , Rahmawati Ayu , Mawaddati Rahmi , Saputra Stanley , Hasnida Amalia , Pisani Elizabeth , Anggriani Yusi , Gheorghe Adrian
Published: September 2024

Background

Substandard and falsified medicines (SFMs) are a public health concern of global importance. Postmarket surveillance in the form of medicine sampling and quality testing can prevent and detect SFM, however, there is remarkably scarce evidence about the cost and value for money of these activities: how much do they cost and how effective are they in detecting SFM?

Methods

Between February and October 2022, Systematic Tracking of At Risk Medicines (STARmeds) collected and analysed for quality 1274 samples of 5 medicines from physical and online retail outlets in 7 Indonesian districts. We collated data on the resources consumed by STARmeds, related to all stages of medicines sampling and quality testing including design, fieldwork and laboratory analysis. We used activity-based costing principles to calculate the financial and economic cost of medicine quality surveillance from the perspective of a hypothetical medicines’ regulator. We calculated the cost per day and per week of fieldwork, per sample collected and per substandard sample. We used bootstrapping to capture uncertainty in the number of samples collected, by seller location type (urban, rural and online).

Results

The total cost of sampling and testing medicines from the market was US$712 964 (current 2022 values). Laboratory costs represented the largest share (70%), followed by other direct costs (12%) and indirect costs (7%). On average, it costs STARmeds US$479 (95% CI US$462 to US$516) to collect one medicine sample and US$5990 (95% CI US$5601 to US$6258) to identify one substandard sample.

Conclusion

Our findings bring urgently needed and novel information on the cost and value for money of medicine quality surveillance. These may support planning and budgeting of the Indonesian pharmaceutical regulator, but also of regulators and researchers elsewhere, particularly in low-income and middle-income settings, as well as international organisations with health regulation and quality of care remits.
Comparing 24-hour IOP fluctuation slope curve between newly diagnosed ocular hypertension and primary open-angle glaucoma
Authors: Zhang Qing , Feng Hui , Zhang Ye , Han Dong , Tang Guangxian , Fan Su Jie , Zhang Hengli , Jiang Jing , Lv Aiguo , Li Shuning
Published: September 2024

Objective

To compare the 24-hour intraocular pressure (IOP) fluctuation slope curve between newly diagnosed patients with ocular hypertension (OHT) and primary open-angle glaucoma (POAG).

Methods and analysis

Newly diagnosed and untreated OHT and POAG patients who underwent 24-hour IOP monitoring were consecutively enrolled in the study. IOP measurements were taken every 2 hours from 8:00 to 6:00 hours the following day using an iCare PRO tonometer. Patients maintained their daily routines, with IOP measured in a seated position during the day and supine at night. The 24-hour IOP fluctuation indices, including peak, trough and overall fluctuation, were calculated. Differences in the 24-hour IOP fluctuation slope curves over time between groups were analysed using a generalised additive mixed model.

Results

46 patients with OHT and 41 with POAG were included. From 2:00 to 10:00 hours, mean IOP increased by 0.69 mm Hg every 2 hours in the POAG group (p<0.0001) and by 0.40 mm Hg in the OHT group (p<0.0001). After 10:00, the IOP showed a downward trend, decreasing by 0.31 mm Hg in the POAG group (p<0.0001) and by 0.17 mm Hg in the OHT group (p=0.0003) every 2 hours. The rate of slope change in the upward phase differed significantly between the groups (0.30 mm Hg per 2 hours; p=0.02), as did the rate in the downward phase (0.14 mm Hg per 2 hours; p for interaction=0.04). Multivariate models showed that each 1 mm Hg increase in circadian and diurnal IOP fluctuation was associated with a 27% and 21% higher likelihood of POAG presence, respectively.

Conclusion

The 24-hour IOP slope curve differed between POAG and OHT, with a steeper slope observed in the POAG group. However, the study is limited by potential confounding factors, reliance on a single 24-hour measurement period and the need for further longitudinal studies to validate these findings.
Individual heterogeneity, educational attainment and cardiovascular mortality: a pooled analysis of Norwegian health surveys
Authors: Nguyen Huong Thu , Moger Tron Anders , Valberg Morten , Degerud Eirik , Page Christian M , LeBlanc Marissa , Næss Øyvind
Published: September 2024

Background

Smoking, physical inactivity, cholesterol level and systolic blood pressure are well-established risk factors for cardiovascular diseases (CVD). However, even among individuals with similar levels of these factors, a substantial degree of variation in risk may still remain. We investigated the variation in this unexplained risk across educational levels.

Methods

The study population (N=451 800) was from Norwegian health surveys and linked to the National Education Database and the Norwegian Cause of Death Registry. We used survival analysis with frailty models to measure unobserved heterogeneity (frailty variation). Models were stratified by three educational levels. We highlight the degree of heterogeneity by presenting Gini coefficients and indicate how much the unobserved heterogeneity differed across levels of education from the estimated parameters of the frailty distributions. Lorenz curves were plotted for a graphical representation of inequalities in individual risk.

Main results

The estimated frailty variances were 24.96, 34.12 and 42.37 in the low, middle and high education groups, respectively, before adjusting for risk factors and 3.76, 7.12 and 7.82 after adjusting for risk factors. The corresponding Gini coefficients were 0.75, 0.84 and 0.86 for low, middle and high education groups, respectively.

Conclusion

A large share of the variation in CVD mortality was explained by the observed risk factors. However, a substantial individual unobserved variation in CVD mortality remained after adjusting for these risk factors. Our findings indicate that the unobserved variation in CVD mortality could vary somewhat between educational groups, but that education does not explain the major share of the remaining substantial heterogeneity.
Mental health symptoms among Dutch elite athletes and their coaches: a cross-sectional study
Authors: Bilgoe Sharaisha Chanita , Moen Maarten H , Raedts Eefje , Upmeijer Judith , Kerkhoffs Gino , Gouttebarge Vincent
Published: September 2024

Objective

To establish the prevalence of mental health symptoms (MHSs) among Dutch elite athletes and their coaches, to examine the association between potential contributing factors and MHS among Dutch elite athletes and their coaches and to explore the view and needs of Dutch elite athletes and their coaches regarding mental health resources and support.

Methods

A cross-sectional study was conducted by distributing an electronic questionnaire based on validated screening questionnaires for the assessment of MHS.

Results

In total, 156 athletes (55% female) and 95 coaches (79% male) across various sports participated in this study. The most prevalent MHS among athletes and coaches were distress (73% and 41%) and alcohol misuse (52% and 53%). Adverse life events showed an association with anxiety, depression, sleep disturbance, alcohol misuse and disordered eating while severe injuries showed an association with distress and sleep disturbance in elite athletes. Among coaches, no significant associations were found between potential contributing factors and MHS. 60% of the athletes and 60% of the coaches (totally) agreed that they could openly address their mental health issues within their sport while 53% of the athletes and 41% of the coaches (totally) agreed a need for increased attention regarding mental health/guidance in their sport.

Conclusions

MHSs are prevalent among Dutch elite athletes and coaches. Recent adverse life events and severe injuries have a potential intersection with MHS in elite athletes. There is a need for increased attention regarding mental health/guidance among Dutch elite athletes and coaches within their sport so that subsequent treatment/support can be provided.
BCMA-BBZ-OX40 CAR-T Therapy Using an Instant Manufacturing Platform in Multiple Myeloma
Authors: Wang Ting , Yang Yazi , Ma Lie , Feng Ru , Li Jiangtao , Zhang Chunli , Bai Jiefei , Ding Yanping , Liu Guanghua , Wu Fei , Lu Xinan , Feng Shi , Li Zhenling , He Ting , Li Jian , Liu Hui
Published: September 2024

Background

Chimeric antigen receptor (CAR)-T cell has revolutionary efficacy against relapsed/refractory multiple myeloma (R/R MM). However, current CAR-T cell therapy has several limitations including long vein-to-vein time and limited viability.

Methods

A 4-1BB-costimulated B-cell maturation antigen (BCMA) CAR-T integrating an independently-expressed OX40 (BCMA-BBZ-OX40) was designed and generated by a traditional manufacturing process (TraditionCART) or instant manufacturing platform (named InstanCART). The tumor-killing efficiency, differentiation, exhaustion, and expansion level were investigated in vitro and in tumor-bearing mice. An investigator-initiated clinical trial was performed in patients with R/R MM to evaluate the outcomes of both TraditionCART and InstanCART. The primary objective was safety within 1 month after CAR-T cell infusion. The secondary objective was the best overall response rate.

Results

Preclinical studies revealed that integrated OX40 conferred BCMA CAR-T cells with superior cytotoxicity and reduced exhaustion levels. InstanCART process further enhanced the proliferation and T-cell stemness of BCMA-BBZ-OX40 CAR-T cells. BCMA-BBZ-OX40 CAR-T cells were successfully administered in 22 patients with R/R MM, including 15 patients with TraditionCART and 7 patients with InstanCART. Up to 50% (11/22) patients had a high-risk cytogenetic profile and 36% (8/22) had extramedullary disease. CAR-T therapy caused grade 1–2 cytokine release syndrome in 19/22 (80%) patients, grade 1 neurotoxicity in 2/22 (9%) patients and led to ≥grade 3 adverse events including neutropenia (20/22, 91%), thrombocytopenia (15/22, 68%), anemia (12/22, 55%), creatinine increased (1/22, 5%), hepatic enzymes increased (5/22, 23%), and sepsis (1/22, 5%). The best overall response rate was 100%, and 64% (14/22) of the patients had a complete response or better. The median manufacturing time was shorter for InstanCART therapy (3 days) than for TraditionCART therapy (10 days). Expansion and duration were dramatically higher for InstanCART cells than for TraditionCART cells.

Conclusions

BCMA-BBZ-OX40 CAR-T cells were well tolerated and exhibited potent responses in patients with R/R MM. InstanCART shortened the manufacturing period compared to TraditionCART, and improved the cellular kinetics. Our results demonstrated the potency and feasibility of OX40-modified BCMA CAR-T cells using InstanCART technology for R/R MM therapy.

Trial registration number

This trial was registered at www.clinicaltrials.gov as #NCT04537442.
MTA-cooperative PRMT5 inhibitors enhance T cell-mediated antitumor activity in MTAP-loss tumors
Authors: Chen Si , Hou Jiakai , Jaffery Roshni , Guerrero Ashley , Fu Rongjie , Shi Leilei , Zheng Ningbo , Bohat Ritu , Egan Nicholas A , Yu Chengtai , Sharif Sana , Lu Yue , He Wei , Wang Shuyue , Gjuka Donjeta , Stone Everett M , Shah Pooja Anil , Rodon Ahnert Jordi , Chen Taiping , Liu Xinli , Bedford Mark T , Xu Han , Peng Weiyi
Published: September 2024

Background

Hyperactivated protein arginine methyltransferases (PRMTs) are implicated in human cancers. Inhibiting tumor intrinsic PRMT5 was reported to potentiate antitumor immune responses, highlighting the possibility of combining PRMT5 inhibitors (PRMT5i) with cancer immunotherapy. However, global suppression of PRMT5 activity impairs the effector functions of immune cells. Here, we sought to identify strategies to specifically inhibit PRMT5 activity in tumor tissues and develop effective PRMT5i-based immuno-oncology (IO) combinations for cancer treatment, particularly for methylthioadenosine phosphorylase (MTAP)-loss cancer.

Methods

Isogeneic tumor lines with and without MTAP loss were generated by CRISPR/Cas9 knockout. The effects of two PRMT5 inhibitors (GSK3326595 and MRTX1719) were evaluated in these isogenic tumor lines and T cellsin vitroandin vivo. Transcriptomic and proteomic changes in tumors and T cells were characterized in response to PRMT5i treatment. Furthermore, the efficacy of MRTX1719 in combination with immune checkpoint blockade was assessed in two syngeneic murine models with MTAP-loss tumor.

Results

GSK3326595 significantly suppresses PRMT5 activity in tumors and T cells regardless of the MTAP status. However, MRTX1719, a methylthioadenosine-cooperative PRMT5 inhibitor, exhibits tumor-specific PRMT5 inhibition in MTAP-loss tumors with limited immunosuppressive effects. Mechanistically, transcriptomic and proteomic profiling analysis reveals that MRTX1719 successfully reduces the activation of the PI3K pathway, a well-documented immune-resistant pathway. It highlights the potential of MRTX1719 to overcome immune resistance in MTAP-loss tumors. In addition, MRTX1719 sensitizes MTAP-loss tumor cells to the killing of tumor-reactive T cells. Combining MRTX1719 and anti-PD-1 leads to superior antitumor activity in mice bearing MTAP-loss tumors.

Conclusion

Collectively, our results provide a strong rationale and mechanistic insights for the clinical development of MRTX1719-based IO combinations in MTAP-loss tumors.
Alexia without agraphia: from infarctions to malignancies
Authors: Jauregui Ruben , Greenberg Julia , Kuball Philip , Newbold Dillan J , Patel Riddhi , Staudinger Robert
Published: September 2024

Alexia without agraphia is a neurological syndrome characterised by an acquired inability to read with a preserved ability to write. It is caused by the combined effect of two lesions: in the splenium of the corpus callosum and in the occipital lobe of the dominant hemisphere. Splenial lesions disconnect the language areas in the temporal and parietal lobes of the dominant hemisphere from the visual areas in the occipital cortex of the contralateral side, while lesions in the dominant occipital lobe cause homonymous hemianopia. We describe two patients with lesions affecting the splenium and dominant occipital lobe, with different causes. Together, these cases highlight the importance of performing a thorough language evaluation in patients presenting with homonymous visual field deficits, as otherwise, clinicians may overlook impairments in writing (agraphia) or reading (alexia).
Insights into the shallow landslide mechanism of expansive soil slope induced by freeze–thaw cycles and snowmelt infiltration
Authors: Cong Shengyi , Tang Liang , Ling Xianzhang , Vanapalli Sai K.
Published: September 2024

For rigorous understanding the shallow landslide mechanisms and deformation characteristics of expansive soil slopes, a comprehensive in-situ monitoring platform is established. Triaxial creep tests and microstructure analysis with scanning electron microscopy are also conducted on expansive soil samples obtained from Binxi station. Field monitoring data indicates that freeze–thaw (F–T) cycle and snowmelt infiltration significantly increase the creep deformation of expansive soil slope during spring melting period. Due to the influence of F–T cycle and snowmelt infiltration, more soil grains are involved in the shear deformation contributing to a large, localized shearing. Additionally, the microstructural analysis shows that F–T cycle influences the relationship between expansive soil grains that gradually change from face–face contact to point–face contact or edge–edge contact form. The shallow landslide mechanisms of expansive soil slope are revealed from creep deformation and microstructure characteristics of soils after the F–T cycle and snowmelt infiltration, which can be summarized into two stages, namely, the snowfall accumulation state and snow melt-shallow infiltration stage. These results can serve as a good reference for the prevention of expansive soil slopes in seasonally frozen regions.
Method for Rendering Large-Scale Movie Late-Stage Special Effects Under Mixed Use of Level of Detail Fusion
Authors: Zhi Yang
Published: September 2024

Large-scale movies often require extensive special effects to captivate audiences. To enhance the realism and quality of these effects, especially in complex scenes, a method combining detail-level fusion for post-special effects rendering is introduced. This method involves creating a detailed hierarchy diagram and a visual information sampling model to sample color-matched visuals and extract auxiliary visual elements. It aims to improve the visual communication of special effects and enable real-time, high-quality rendering. Experimental results demonstrate that this approach delivers higher resolution, better quality in film production, consistent output, stability across various scenes, and superior rendering and tracking capabilities, with higher recall and comprehensive evaluation scores, as well as enhanced visual effects.
Research on Enterprise Financial Information Risk Identification and Dynamic Control Management Model Based on Genetic Algorithm
Authors: Deng Xiao-yan
Published: September 2024

In the contemporary global economic landscape, the imperative for enterprise financial informatization as a catalyst for efficiency, cost reduction, and innovation is evident. However, the deepening integration of informatization introduces corresponding risks, necessitating the establishment of effective risk management systems. This paper proposes a genetic algorithm-based model for enterprise financial informatization risk management, aiming to offer precise and actionable solutions. The study integrates genetic algorithms to enhance the adaptability and flexibility of the risk management model in the dynamic information environment. Through in-depth research on corporate financial informatization risks, a multi-dimensional risk management control model is constructed, considering technical, organizational, and environmental factors. The genetic algorithm introduces a new perspective for model optimization, enabling efficient search and optimization capabilities. The model not only identifies but also controls and governs risks, providing timely intervention and effective risk management. Moreover, the genetic algorithm facilitates intelligent decision support for risk management by adapting to changing environments. Empirical analysis validates the model’s feasibility and effectiveness in real enterprise cases, emphasizing its practicality.
Fairness and Bias in Algorithmic Hiring: A Multidisciplinary Survey
Authors: Fabris Alessandro , Baranowska Nina , Dennis Matthew J. , Graus David , Hacker Philipp , Saldivar Jorge , Zuiderveen Borgesius Frederik , Biega Asia J.
Published: September 2024

Employers are adopting algorithmic hiring technology throughout the recruitment pipeline. Algorithmic fairness is especially applicable in this domain due to its high stakes and structural inequalities. Unfortunately, most work in this space provides partial treatment, often constrained by two competing narratives, optimistically focused on replacing biased recruiter decisions or pessimistically pointing to the automation of discrimination. Whether, and more importantly
what types of
, algorithmic hiring can be less biased and more beneficial to society than low-tech alternatives currently remains unanswered, to the detriment of trustworthiness. This multidisciplinary survey caters to practitioners and researchers with a balanced and integrated coverage of systems, biases, measures, mitigation strategies, datasets, and legal aspects of algorithmic hiring and fairness. Our work supports a contextualized understanding and governance of this technology by highlighting current opportunities and limitations, providing recommendations for future work to ensure shared benefits for all stakeholders.
Pathways to Belonging: Understanding How University Entry Routes Shape the Sense of Belonging of Undergraduate Computing Students
Authors: Runa Shamima Nasrin , McCartan Andrew , Becker Brett A. , Mooney Catherine
Published: September 2024

Sense of belonging, or belongingness in academia, is an individual's personal conviction as to their acceptance as a valued member of an academic community. The importance of belongingness lies in correlations with motivation, persistence, mental health and well-being. Prior work has shown that belongingness can be lower in students who are minoritised due to their gender, race, nationality, socio-economic status, religion and/or disability. However, there is limited research on how a student's university entry route impacts their sense of belonging in Computer Science and Other Science disciplines. In Ireland's higher education system, university entry is primarily managed through the Central Applications Office (CAO) process, which predominantly serves students transitioning directly from secondary school to university. Additionally, alternative access routes are available for students from socio-economically disadvantaged backgrounds, those with disabilities, and mature students. At University College Dublin (UCD), entry is facilitated through both the traditional direct-entry school leaving route and combined access routes, each serving distinct student demographics. To investigate how these varying entry routes influence students’ sense of belonging, we utilised a survey adapted from the validated ‘Math Sense of Belonging Scale’ to examine the belongingness of undergraduate Science students, including Computer Science students. We examined how the belongingness of students varies by university entry route, and how the belongingness of students in Computer Science varies by university entry route compared to Other Science students. Our results reveal a significant difference in belongingness between students entering university through the direct-entry school leaving route, compared to those who entered via combined access routes (e.g. university admissions schemes for school leavers from socio-economically disadvantaged backgrounds, with disabilities, and mature students). Specifically, within Computer Science, students entering university through the direct-entry school leaving route had significantly higher belongingness than combined access route students. These results provide insight that may help others improve the belongingness of undergraduate Computer Science students.
Pentaerythritol-Based Compound as a Novel Leveler for Super-Conformal Copper Electroplating
Authors: Chen Zumin , Li Zhen , Liu Cui , Zhan Anda , Luo Jiye , Shi Daniel
Published: September 2024

Leveler is one of the most important organic additives in copper electroplating for microvia filling. To enhance the microvia filling efficiency and reduce the bath control difficulty, novel levelers with high filling performance and wide application concentration range has long been pursued. Herein, a novel leveler named L1 with four pyrrolidine rings linked by a pentaerythritol backbone is designed and synthesized. Compared with the previously reported leveler TPM-1, L1 shares the same nitrogen-containing group but has an additional pyrrolidine ring. The structure-property relationship of L1 is thoroughly characterized by electrochemical measurements, theoretical calculations, and electroplating experiments. Results show that with one more positively charged ammonium groups, L1 exhibits stronger interactions with Cl− and the accelerator SPS compared to TPM-1. However, due to the variation of the connecting group, its interaction with the suppressor PEG is much weaker. With L1 as the leveler, both good microvia filling performance and high-quality copper deposition was obtained within a wide concentration range. The findings indicate that L1 is a very promising leveler for microvia filling copper electroplating, and both nitrogen-containing groups and linking groups in a leveler significantly influence its properties and performances.
Evaluation of the Efficacy and Safety of Oral Tofacitinib for the Treatment of Alopecia Areata in Children
Authors: Abedini Robabeh , Al-Zahawi Saman , Dehghan Soroosh , Ghandi Narges , Nasimi Maryam , Razavi Zahra
Published: September 2024

Alopecia areata (AA) is a common chronic relapsing nonscarring alopecia. Severe forms of AA commonly manifest during childhood. Treatment of AA is challenging due to the variability of the disease course as well as unpredictable responses to treatment. There is no uniform approved treatment for cure or sustained remission in children till now. Tofacitinib emerged as a novel drug in the treatment of AA, but few studies have been conducted on its safety and efficacy in children. Limitation of this study includes retrospective nature, small sample size, and lack of prolonged follow‐up. Aim. This retrospective study aimed to assess the efficacy and safety of oral tofacitinib in children with AA. Method. In this retrospective study, we included patients aged 18 years or younger with AA. The scalp blandness of included patients was greater than 20% and they were on oral tofacitinib for at least two months. The demographic data, clinical characteristics, tofacitinib efficacy, and adverse effects were recorded. The primary endpoint was the last recorded percent change in the Severity of Alopecia Tool (SALT) score during treatment. Results. We included 26 patients (12 males and 14 females) with AA with a mean age of 11.6 ± 4.42 (3–18) years. Eighteen of them were in the alopecia areata (AA) group, whereas eight patients had alopecia totalis (AT) or alopecia universalis (AU). The mean disease duration before starting treatment with tofacitinib was 3.9 ± 3.3 years. Most of the patients were on a tofacitinib daily dose of 5 mg (53.85%) and 10 mg (38.46%). Patients were on tofacitinib for 6.73 ± 3.79 months. The patients’ baseline SALT score was recorded as 68.58 ± 32.65 and the final SALT score was 17.65 ± 23.88. Thus, the patients achieved a 50.92% reduction in the SALT score. Interestingly, there were no statistically significant differences in clinical efficacy between subtypes of AA and AT/AU. Conclusion. Tofacitinib was significantly effective in treating AA and AT/AU in children, with mild tolerable adverse effects, although relapse during treatment and tapering was recorded. Future randomized clinical trials with longer follow‐up periods are needed to evaluate the safety of oral tofacitinib in children.
The Influence of Biochar, Organic and Inorganic Fertilizers, and Arbuscular Mycorrhizal Fungi Inoculation on Maize Crop Performance Under Normal and Water‐Stressed Conditions
Authors: Zenebe Buticha , Dobo Beyene , Woliy Kedir
Published: September 2024

Water scarcity limits the amount of maize that can be produced in Ethiopia and around the world. This study was aimed to investigate the effects of amendment application and arbuscular mycorrhizal fungi (AMF) inoculation on maize growth and biomass yield in a greenhouse under both normal and water‐stressed conditions. Biochar, organic matter, and blended inorganic fertilizer (NPSB) were added as amendments. Inoculation of Gigaspora rosea and Rhizophagus clarus with the application of NPSB under normal watering has resulted in maximum heights of 96.7 and 115.0 cm, respectively. When they were subjected to water stress, their maximum heights were 65.7 and 68.01 cm. The leaf number in NPSB fertilization under regular watering was 13.3, comparable to 13.7 in R. clarus + OM and R. clarus + biochar + OM + NPSB. Under normal watering, G. rosea + NPSB and R. clarus + NPSB demonstrated the highest aboveground biomass yields of 57.7 and 47.8 g, respectively. In comparison to the control, G. rosea and R. clarus + NPSB demonstrated the highest yields of 52.9 and 42.8 g. The treatments involving G. rosea + biochar + OM + NPSB and R. clarus + biochar + OM + NPSB exhibited a greater leaf area index of 31.42 and 26.8, respectively. The treatments that were inoculated with G. rosea also showed improvements in root colonization and spore density. The study’s findings showed that both a single and a combination AMF inoculation improved every growth parameter that was looked at. To find out how well native AMF can boost maize plant yield in both normal and water‐stressed environments, more research is necessary.
A Precise Analysis of the Behavior of Pit Side Tunnels Caused by Deep Excavation
Authors: Sun Huasheng , Zhao Yuexin , Chen Yadong , Li Jiahui
Published: September 2024

As urbanization gathers pace, projects involving adjacent subway tunnels are increasing, thereby amplifying the need for robust tunnel protection measures. Currently, there exists a notable lack of precise analyses on the three‐dimensional (3D) deformation laws and mechanisms of tunnels affected by adjacent deep excavation. Moreover, the influence patterns of retaining wall stiffness and deep excavation depth on the 3D deformation of pit‐side tunnels remain unclear. The purpose of this research is to bridge the existing disparity by adopting the hypoplastic model, which effectively captures soil stiffness that is dependent on soil state, strain, and stress path, even at small strains, as well as soil strength, based on reported centrifuge model tests. This approach facilitates a comprehensive, precise numerical analysis of the interaction between deep excavation and preexisting tunnels located outside the retaining wall. The analysis sheds light on the deformation mechanisms and trends of pit‐side tunnels not solely confined to the longitudinal axis but extending to the transverse plane as well, while systematically examining the influence of varying excavation depths and retaining wall stiffness on key tunnel parameters, including longitudinal deformation, diameter changes, bending strains, and soil pressure distributions around the tunnels. The study reveals that if the tunnel situated outside the retaining structure lies beneath the foundation pit’s base, deep excavation only slightly deforms the tunnel. However, when the tunnel outside the retaining structure is positioned above the pit’s base, its deformation progressively intensifies with deeper excavation, but the growth rate has a decreasing trend. An enhancement in the stiffness of the retaining wall results in a notable decrease in the deformation exhibited by the adjacent tunnels. The findings contribute to a deeper understanding of the complex responses of pit‐side tunnels to excavation activities, ultimately facilitating the design and construction of safer and more resilient urban subway infrastructure.