bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost–utility analysis of commonly used anti-glaucoma interventions for mild-to-moderate primary open-angle glaucoma patients in rural and urban China
Authors: Li Ruyue , Zhang Kaiwen , Lu Zhecheng , Mou Dapeng , Wang Jin , Li Huiqi , Fan Sujie , Wang Ningli , Liu Hanruo
Published: September 2023

Objective

An increasing number of studies have explored the clinical effects of antiglaucoma surgical procedures; however, economic evidence was scarce. We aimed to compare the cost-effectiveness between maximal medical treatment (MMT) and commonly used surgical procedures (trabeculectomy, Ahmed glaucoma valve implantation, gonioscopy-assisted transluminal trabeculotomy and ab interno canaloplasty).

Design and setting

A Markov model study.

Participants

A hypothetical cohort of 100 000 patients with mild-to-moderate primary open-angle glaucoma (POAG).

Outcomes

Data were obtained from public sources. The main outcomes were incremental cost–utility ratios (ICURs) using quality-adjusted life-years (QALYs). Sensitivity analyses were conducted to verify the robustness and sensitivity of base-case results.

Main results

Both cumulative costs and QALYs gained from surgical procedures (US$6045–US$13 598, 3.33–6.05 QALYs) were higher than those from MMT (US$3117–US$6458, 3.14–5.66 QALYs). Compared with MMT, all surgical procedures satisfied the cost-effectiveness threshold (lower than US$30 501 and US$41 568 per QALY gained in rural and urban settings, respectively). During the 5-year period, trabeculectomy produced the lowest ICUR (US$21 462 and US$15 242 per QALY gained in rural and urban settings, respectively). During the 10-year-follow-up, trabeculectomy still produced the lowest ICUR (US$13 379 per QALY gained) in urban setting; however, gonioscopy-assisted transluminal trabeculotomy (US$19 619 per QALY gained) and ab interno canaloplasty (US$18 003 per QALY gained) produced lower ICURs than trabeculectomy (US$19 675 per QALY gained) in rural areas. Base-case results were most sensitive to the utilities and costs of initial treatment and maintenance.

Conclusions

The long-term cost-effectiveness of commonly used surgical procedures could be better than the short-term cost-effectiveness for mild-to-moderate POAG patients in China. Health economic studies, supported by more rigorous structured real-world data, are needed to assess their everyday cost-effectiveness.
Epidemiology of extrapulmonary tuberculosis in Brunei Darussalam: a retrospective cohort study
Authors: Chaw Liling , Mat Salleh Lena , Abdul Hamid Rafizah , Thu Kyaw
Published: September 2023

Objectives

We reported the incidence and associated factors of extrapulmonary tuberculosis (EPTB).

Design

A retrospective cohort study.

Setting

Brunei Darussalam, an intermediate tuberculosis (TB)-burden country with stagnating annual TB rates.

Participants

All active TB cases identified in the country between January 2001 and December 2018 (18 years).

Primary and secondary outcome measures

Annual proportions of EPTB (overall and specific) were calculated. Multiple logistic regression was done to investigate factors associated with developing EPTB, when compared with pulmonary TB (PTB). Χ2trend test was used to determine any trends during the 18-year study period.

Results

We identified 3916 TB cases, among which 743 (19.0%) were EPTB cases. Lymphatic (44.8%) and pleural (19.4%) EPTB were most common. The main modes of diagnosis were tissue biopsy (73.6%) and radiological assessment (18.3%). Treatment success and mortality rate were 79.7% and 7.0%, respectively. Associations with specific EPTB types varies with age-group and gender. Younger age-group (adjusted OR (aOR)≥1.94) and women (aOR: 2.45 (95% CI: 1.94 to 3.11)) had higher adjusted odds of developing lymphatic EPTB, but had lower adjusted odds of developing pleural EPTB (younger age-group (aOR≤0.54) and women (aOR: 0.41 (95% CI: 0.17 to 0.90)). When compared to foreign residents, locals had higher adjusted odds of skeletal (aOR: 4.44 (95% CI: 2.04 to 11.69)), gastrointestinal (aOR: 3.91 (95% CI: 1.84 to 9.66)) and other types of EPTB (aOR: 3.42 (95% CI: 1.53 to 9.14)). No significant trend differences were observed for overall and specific EPTB types.

Conclusion

Despite being generally non-infectious and less recognised than PTB, understanding EPTB epidemiology is important as it also contributes to the overall TB burden in a country. Examining EPTB cases by their specific anatomical site would provide more information on risk factors. Raising public awareness on the EPTB symptoms and that TB affects lungs and other parts of the body could promote early health seeking behaviour and early EPTB diagnosis.
Dual hormone fully closed loop in type 1 diabetes: a randomised trial in the Netherlands – study protocol
Authors: Jancev Milena , Snoek Frank J , Frederix Geert W J , Knottnerus Heleen , Blauw Helga , Witkop Maureen , Moons Karel G M , van Bon Arianne C , DeVries J Hans , Serné Erik H , van Sloten Thomas T , de Valk Harold W
Published: September 2023

Introduction

The management of type 1 diabetes (T1DM) has undergone significant advancements with the availability of novel technologies, notably continuous and flash glucose monitoring (CGM and FGM, respectively) and hybrid closed loop (HCL) therapy. The dual hormone fully closed loop (DHFCL) approach with insulin and glucagon infusion has shown promising effects in small studies on glycaemic regulation and quality of life in T1DM.

Methods and analysis

The Dual Hormone Fully Closed Loop for Type 1 Diabetes (DARE) study is a non-commercial 12-month open-label, two-arm randomised parallel-group trial. The primary aim of this study is to determine the long-term effects on glycaemic control, patient-reported outcome measurements and cost-effectiveness of the DHFCL compared with usual care, that is, HCL or treatment with multiple daily insulin injections+FGM/CGM. We will include 240 adult patients with T1DM in 14 hospitals in the Netherlands. Individuals will be randomised 1:1 to the DHFCL or continuation of their current care.

Ethics and dissemination

Ethical approval has been obtained from the Medical Research Ethics Committee NedMec, Utrecht, the Netherlands. Findings will be disseminated through peer-reviewed publications and presentations at local, national and international conferences.

Trial registration number

NCT05669547.
Ultrasonography in thoracic and abdominal stab wound injury: results from the FETTHA study
Authors: Bouzid Donia , Tran-Dinh Alexy , Lortat-Jacob Brice , Atchade Enora , Jean-Baptiste Sylvain , Tashk Parvine , Snauwaert Aurelie , Zappella Nathalie , Augustin Pascal , Pellenc Quentin , Castier Yves , Ribeiro Lara , Gaudemer Augustin , Khalil Antoine , Montravers Philippe , Tanaka Sebastien
Published: September 2023

Background

While the role of Extended Focused Assessment with Sonography in Trauma (eFAST) is well defined in the management of severe blunt trauma, its performance in injuries caused by stab wounds has been poorly assessed.

Methods

Prospective single centre study which included all patients with stab wounds to the thorax or abdomen between December 2016 and December 2018. All patients underwent initial investigation with both eFAST and CT scan, except in cases of haemodynamic or respiratory instability, and in cases with a positive diagnosis by eFAST in which case surgery without CT scan was performed.

Results

Of the 200 consecutive patients included, 14 unstable patients underwent surgery immediately after eFAST. In these 14 patients, 9 had cardiac tamponade identified by eFAST and all were confirmed by surgery. In the remaining 186 patients, the median time between eFAST and CT scan was 30 min (IQR 20–49 min). Test characteristics (including 95% CI) for eFAST compared with reference standard of CT scan for detecting pneumothorax were as follows: sensitivity 77% (54%–92%), specificity 93% (90%–97%), positive predictive value (PPV) 60% (49%–83%), negative predictive value (NPV) 97% (93%–99%). Test characteristics (including 95% CI) for eFAST compared with CT scan for detecting haemothorax were as follows: sensitivity 97% (74%–99%), specificity 96% (92%–98%), PPV 83% (63%–93%) and NPV 99% (96%–100%). Finally, test characteristics (including 95% CI) for eFAST compared with CT scan for detecting haemoperitoneum were as follows: sensitivity 75% (35%–97%), specificity 97% (93%–99%), PPV 55% (23%–83%) and NPV 99% (96%–99%).

Conclusions

In patients admitted with stab wounds to the torso, eFAST was not sensitive enough to diagnose pneumothorax and haemoperitoneum, but performed better in the detection of cardiac tamponade and haemothorax than the other injuries. More robust multicentre studies are needed to better define the role of eFAST in this specific population.
Prehospital early warning scores for adults with suspected sepsis: retrospective diagnostic cohort study
Authors: Goodacre Steve , Sutton Laura , Thomas Ben , Hawksworth Olivia , Iftikhar Khurram , Croft Susan , Fuller Gordon , Waterhouse Simon , Hind Daniel , Bradburn Mike , Smyth Michael Anthony , Perkins Gavin D , Millins Mark , Rosser Andy , Dickson Jon M , Wilson Matthew Joseph
Published: September 2023

Background

Ambulance services need to identify and prioritise patients with sepsis for early hospital assessment. We aimed to determine the accuracy of early warning scores alongside paramedic diagnostic impression to identify sepsis that required urgent treatment.

Methods

We undertook a retrospective diagnostic cohort study involving adult emergency medical cases transported to Sheffield Teaching Hospitals ED by Yorkshire Ambulance Service in 2019. We used routine ambulance service data to calculate 21 early warning scores and categorise paramedic diagnostic impressions as sepsis, infection, non-specific presentation or other presentation. We linked cases to hospital records and identified those meeting the sepsis-3 definition who received urgent hospital treatment for sepsis (reference standard). Analysis determined the accuracy of strategies that combined early warning scores at varying thresholds for positivity with paramedic diagnostic impression.

Results

We linked 12 870/24 955 (51.6%) cases and identified 348/12 870 (2.7%) with a positive reference standard. None of the strategies provided sensitivity greater than 0.80 with positive predictive value greater than 0.15. The area under the receiver operating characteristic curve for the National Early Warning Score, version 2 (NEWS2) applied to patients with a diagnostic impression of sepsis or infection was 0.756 (95% CI 0.729, 0.783). No other early warning score provided clearly superior accuracy to NEWS2. Paramedic impression of sepsis or infection had sensitivity of 0.572 (0.519, 0.623) and positive predictive value of 0.156 (0.137, 0.176). NEWS2 thresholds of >4, >6 and >8 applied to patients with a diagnostic impression of sepsis or infection, respectively, provided sensitivities and positive predictive values of 0.522 (0.469, 0.574) and 0.216 (0.189, 0.245), 0.447 (0.395, 0.499) and 0.274 (0.239, 0.313), and 0.314 (0.268, 0.365) and 0.333 (0.284, 0.386).

Conclusion

No strategy is ideal but using NEWS2 alongside paramedic diagnostic impression of infection or sepsis could identify one-third to half of sepsis cases without prioritising unmanageable numbers. No other score provided clearly superior accuracy to NEWS2.

Trial registration number

researchregistry5268,https://www.researchregistry.com/browse-the-registry%23home/registrationdetails/5de7bbd97ca5b50015041c33/
Remission, response, retention and persistence to treatment with disease-modifying agents in patients with rheumatoid arthritis: a study of harmonised Swedish, Danish and Norwegian cohorts
Authors: Westerlind Helga , Glintborg Bente , Hammer Hilde Berner , Saevarsdottir Saedis , Krogh Niels Steen , Hetland Merete Lund , Hauge Ellen-Margrethe , Martinez Tejada Isabel , Sexton Joseph , Askling Johan
Published: September 2023

Objective

Precision medicine in rheumatoid arthritis (RA) requires a good understanding of treatment outcomes and often collaborative efforts that call for data harmonisation. We aimed to describe how harmonisation across study cohorts can be achieved and investigate how the observed proportions reaching remission vary across remission criteria, study types, disease-modifying antirheumatic drugs (DMARDs) and countries, and how they relate to other treatment outcomes.

Methods

We used data from eight existing large-scale, clinical RA registers and a pragmatic trial from Sweden, Denmark and Norway. In these, we defined three types of treatment cohorts; methotrexate monotherapy (as first DMARD), tumour necrosis factor inhibitors (TNFi) (as first biological DMARD) and rituximab. We developed a harmonised study protocol defining time points during 36 months of follow-up, collected clinical visit data on treatment response, retention, persistence and six alternative definitions of remission, and investigated how these outcomes differed within and between cohorts, by treatment.

Results

Cohort sizes ranged from ~50 to 22 000 patients with RA. The proportions reaching each outcome varied across outcome metric, but with small to modest variations within and between cohorts, countries and treatment. Retention and persistence rates were high (>50% at 1 year), yet <33% of patients starting methotrexate or TNFi, and only 10% starting rituximab, remained on drug without other DMARDs added and achieved American Congress of Rheumatology/European Alliance of Associations for Rheumatology or Simplified Disease Activity Index remission at 1 year.

Conclusion

Harmonisation of data from different RA data sources can be achieved without compromising internal validity or generalisability. The low proportions reaching remission, point to an unmet need for treatment optimisation in RA.
Phosphatidylinositol-specific phospholipase C can decrease Müller cell viability and suppress its phagocytic activity by modulating PI3K/AKT signaling pathway
Authors: Sun Bianjin , Lin Shudan , Zheng Mengmeng , Zheng Beijia , Mao Liping , Gu Yunfeng , Cai Jiabei , Dai Yiran , Zheng Meiqin , Lou Yongliang
Published: September 2023

Bacillus cereus endophthalmitis is a devastating eye infection that causes rapid blindness through the release of extracellular tissue-destructive exotoxins. The phagocytic and antibacterial functions of ocular cells are the keys to limiting ocular bacterial infections. In a previous study, we identified a new virulence gene, plcA-2 (different from the original plcA-1 gene), that was strongly associated with the plcA gene of Listeria monocytogenes. This plcA gene had been confirmed to play an important role in phagocytosis. However, how the Bc-phosphatidylinositol-specific phospholipase C (PI-PLC) proteins encoded by the plcA-1/2 genes affect phagocytes remains unclear in B. cereus endophthalmitis. Here, we found that the enzymatic activity of Bc-PI-PLC-A2 was approximately twofold higher than that of Bc-PI-PLC-A1, and both proteins inhibited the viability of Müller cells. In addition, PI-PLC proteins reduced phagocytosis of Müller cells by decreasing the phosphorylation levels of key proteins in the PI3K/AKT signaling pathway. In conclusion, we showed that PI-PLC proteins contribute to inhibit the viability of and suppress the phagocytosis of Müller cells, providing new insights into the pathogenic mechanism of B. cereus endophthalmitis.
Degree of nearly comonotone approximation of periodic functions
Authors: Dzyubenko German
Published: September 2023

Let a [Formula: see text]-periodic function [Formula: see text] change its monotonicity at a finitely even number of points [Formula: see text] of the period. The degree of approximation of this [Formula: see text] by trigonometric polynomials which are comonotone with it, i.e. that change their monotonicity exactly at the points [Formula: see text] where [Formula: see text] does, is restricted by [Formula: see text] (with a constant depending on the location of these [Formula: see text]). Recently, we proved that relaxing the comonotonicity requirement in intervals of length proportional to [Formula: see text] about the points [Formula: see text] (so-called nearly comonotone approximation) allows the polynomials to achieve the approximation rate of [Formula: see text]. By constructing a counterexample, we show that even with the relaxation of the comonotonicity requirement for the polynomials on sets with measures approaching [Formula: see text], [Formula: see text] is not reachable.
Interferometric Determination for Cosmological and Stellar Phenomena
Authors: Lerner P. B. , Cutler P. H. , Miskovsky N. M. , Sullivan T. E. , Mayer A.
Published: September 2023

The development of experimental methods that distinguish between light from objects with a similar color temperature and polarization presents a significant practical problem. In this paper, we demonstrate that the two-point correlation function (and its resultant correlation length) of a black body with an extended angular spectrum significantly differs from that of a black body with a narrow angular one. Using these results, we discuss an interferometric method as a possible experimental tool for discriminating between objects with the same color temperature but having different angular spectra.
Chinese Event Discourse Deixis Resolution: Design of the Dataset and Model
Authors: Xie Dongdong , Li Fei , Li Bobo , Teng Chong , Ji Donghong , Zhang Meishan
Published: September 2023

Anaphora resolution is a traditional task in the natural language processing community, defined as a cohesion phenomenon where one entity points back to a previous entity. Event discourse deixis (EDD) is a kind of more complex anaphora in which the anaphors refer to event descriptions such as sentences or clauses. Event discourse deixis resolution (EDDR) is able to help machines understand the richer linguistic and semantic information in the discourse. However, compared to anaphora resolution, EDDR has received relatively less research attention. In this work, we investigate the EDDR task by designing the corresponding dataset and model. First, we manually construct a high-quality Chinese corpus for EDDR, including 4,417 documents and 5,929 event chains that consist of event antecedents and anaphors. Second, we propose a deep neural network model for EDDR, which formulates the task into two subtasks, namely event anaphor recognition and event antecedent recognition. Our model is trained under the two subtasks jointly so that the EDDR task can be performed end to end. Besides our final model, we also build seven pipeline and joint models as baselines to build comprehensive benchmarks for follow-up research. Experimental results on our EDDR dataset show that our model outperforms all the baselines and achieves about 53%, 44%, 53%, and 63% F1s using standard anaphora resolution metrics such as CoNLL, MUC, B3, and Ceafe. The performances show that EDDR is a challenging task and worth researching in the future. Our dataset and model will be released to facilitate follow-up research.
MHG-ERC: Multi-hypergraph Feature Aggregation Network for Emotion Recognition in Conversations
Authors: Zheng Cheng , Xu Haojie , Sun Xiao
Published: September 2023

The modeling of conversational context is an essential step in Emotion Recognition in Conversations (ERC). To maintain high performance and a low GPU memory consumption, this article proposes a new idea of using multiple hypergraphs to model the conversational context and designs a multi-hypergraph feature aggregation network for ERC. We use context window, speaker information, position information between utterances, and specific step size to construct different hyperedges. Then, various hypergraphs generated by different hyperedges are used to aggregate local and remote context information in turn. Experiments on two dialogue emotion datasets, IEMOCAP and MELD, demonstrate the effectiveness and superiority of this new model. In addition, our model requires only relatively low GPU memory consumption.
Enabling Jet-Electrochemical Discharge Machining on Niobium-Like Passivating Metal and the Single Step Fabrication of Coated Microstructures
Authors: Lu Jiajun , Liu Sanjun , Zhao Yonghua
Published: September 2023

Analogous to difficult-to-cut materials in mechanical machining, Niobium (Nb) is a difficult-to-dissolve metal by electrochemical machining (ECM) due to its prone-to-passivation nature. Jet-electrochemical discharge machining (Jet-ECDM), which uses anodic discharge rather than the cathodic discharge as in traditional ECDM, has been previously demonstrated as an efficient method for machining inert semiconductors like Si, 4H-SiC. However, applying Jet-ECDM on Nb-like passivating metal is very challenging because plasma electrolytic oxidation (PEO) is very prone to occur in the machining area due to anodic discharges, forming an insoluble, highly stable oxide coating that prevents material removal. This study reveals the principles of overcoming PEO to enable Jet-ECDM on metals. The findings show that the discharge intensity, affected by the electric field and pulse frequency, is decisive in achieving Nb material removal. The electrolyte chemistry significantly influences material removal fashions, depending on the electrolyte’s chemical activity. NaOH is the preferred choice for higher removal efficiency (maximum 1.92 mm min−1) and machining localization, while NaCl ensures better surface quality (Sa 99.4 nm). Moreover, the Jet-ECDM generated microstructure surface presents a thin layer of PEO coatings (<1 μm). This demonstrates the high potential of Jet-ECDM technology for efficient fabrication of coated microstructures in a single-step process.
The Nature of Field Particle FiPa
Authors: Alfarisi Omar
Published: September 2023

What is the nature of the field? What is the nature of the electromagnetic field or gravity field? Is it possible that a field would be the smallest particle that we have not yet been able to reach, or is it not possible? Would it be tiny particles defusing out of photons (perpendicularly), producing Electric fields (E) and Magnetic fields (M), while a gravity field keeps these tiny particles connected to that photon?These questions are related to the following hypothesis of the Electro-Magnetic-Gravity (EMG) field that we perform testing for. We investigate if E, M, G, EM, and EMG Fields are made of tiny particles named the Field Particle (FiPa). The research is divided into sections. In one section, we explore the EM-Field morphology and its FiPa and whether it defuses out of photons. In another section, we research whether each field has its own FiPa or if there is only one type of FiPa for all fields. In another section, I dedicate the research to investigating the Gravity Field tiny Particles (GFiPa) and whether it keeps the connection between EM-Field tiny Particles (EM-FiPa) and the Photon. For this research paper, we focus on investigating the existence of Field Particles (FiPa). Therefore, we start by exploring one of the fields, the Magnetic Field, to discover its FiPa if it exists.
Vasoactive mediators of hypertension in obesity
Authors: Ghanim Husam , Thethi Tina K. , Abuaysheh Sanaa , Fonseca Vivian , Dandona Paresh
Published: September 2023

Our data show that obesity, especially morbid obesity, is associated with higher blood pressure levels and increases angiotensin II and endotherlin-1 (ET-1) (vasoconstrictors) and lower levels BNP and cGMP (vasodilators) and that systolic blood pressure variability can be partly explained by levels of angiotensin II, aldosterone, renin, and ET-1. The effect of these mediators on blood pressure is in addition to the effects of other known factors related to age, male gender, and AA race.
Candidate Oligo Therapeutic Target, miR-330-3p, Induces Tamoxifen Resistance in Estrogen Receptor-Positive Breast Cancer Cells via HDAC4
Authors: Zhang Meng , Wang Mei , Jiang Zhiming , Fu Ziyi , Ma Jingjing , Gao Sheng
Published: September 2023

Tamoxifen is a drug used for treating breast cancer (BC), especially for individuals diagnosed with estrogen receptor-positive (ER+) BC. Its prolonged use could reduce the risk of recurrence and significantly lengthen the survival rate of BC patients. However, an increasing number of patients developed resistance to tamoxifen treatment, which reduced therapeutic efficiency and caused substandard prognosis. Therefore, the exploration of the molecular processes involved in tamoxifen resistance (TR) is urgently required. This investigation aimed to elucidate the relationship of microRNA-330 (miR-330-3p) with the TR of BC. There is little information on miR-330-3p′s link with drug-resistant BC, although it is well known to regulate cell proliferation and apoptosis. Primarily, miR-330-3p expression in parental BC (MCF7/T47D), TR (MCF7-TR), and T47D/TR cell lines was detected by qRT-PCR. Then, the impact of miR-330-3p on the TR of BC cells was assessed by a cell proliferation assay. Lastly, dual-luciferase reporter, qRT-PCR, and western blot assessments were carried out to identify histone deacetylase 4 (HDAC4) as the potential miR-330-3p target gene. The data indicated that miRNA-330 was overexpressed in TR ER+ BC cells and its overexpression could induce TR. Furthermore, miRNA-330 could also reduce the expression of HDAC4, which is closely linked to TR, and overexpression of HDAC4 could reverse miRNA-330-induced drug resistance. In summary, miR-330-3p could induce TR of ER+ BC cells by downregulating HDAC4 expression, which might be a novel marker of TR and a possible treatment target against BC patients who are tamoxifen-resistant.
Micronutrients and Nutrition Status of School-Aged Children in Indonesia
Authors: Ernawati Fitrah , Efriwati  , Nurjanah Nunung , Aji Galih Kusuma , Hapsari Tjandrarini Dwi , Widodo Yekti , Retiaty Fifi , Prihatini Mutiara , Arifin Aya Yuriestia , Sundari Dian , Rachmalina Rika , Salimar  , Julianti Elisa Diana , Aidi Muhammad Nur , Syauqy Ahmad
Published: September 2023

Micronutrient deficiencies (MNDs) in school-aged children are still a major health problem in Indonesia. This study was designed to examine the status of micronutrients and their relationship to the nutritional status of children aged 5–12 years since an up-to-date database on the micronutrient status of children aged 5–12 years is needed. Data from the 2018 Indonesian Basic Health Research (Riskesdas) were used in this study, with 2456 subjects for analysis. Micronutrient analysis was carried out, including iron status (ferritin, C reactive protein (CRP)), levels of zinc, vitamin D, calcium, and vitamin A (retinol) in school-aged children (5–12 years). The ELISA measurement was applied to measure CRP, ferritin, and vitamin D. Zinc levels were analysed with atomic absorbance spectroscopy (AAS). Moreover, high-performance liquid chromatography (HPLC) was applied to calculate vitamin A. In addition, stunting and thinness data were also obtained from the Riskesdas study. The results showed that the prevalence of stunting and thinness in school-aged children was 11.4% and 9.2%, respectively, showing that the stunting prevalence in the city was lower than in the village (4.5% vs. 6.9%,P = 0.000, respectively). In addition, the prevalence of MNDs in Indonesian children was 13.4%, 19.7%, 4.2%, 3%, and 12.7% for ferritin, zinc, calcium, vitamin A, and vitamin D, respectively. The mean serum level of vitamin A and zinc was significantly lower in stunted children compared to normal school children (P = 0.010 andP = 0.014). The serum concentration of vitamin D was significantly lower in overweight children compared to thin and normal children (P = 0.000). Serum values of ferritin, zinc, and vitamin A were significantly higher in overweight children compared to thin and normal children (P = 0.000). A poor correlation was observed between the z-score of height-for-age (HAZ) and the levels of zinc (r = 0.089,P = 0.000), vitamin A (r = 0.105,P = 0.000), and vitamin D (−0.073,P = 0.000). In addition, very weak correlations between z-scores of body mass index-for-age (BAZ) and the serum concentrations of ferritin (0.091,P = 0.000), zinc (r = 0.115,P = 0.000), vitamin A (r = 0.137,P = 0.000), and vitamin D (r = −0.112,P = 0.000) were also seen. In conclusion, school-aged children in Indonesia experienced stunting, thinness, and micronutrient deficiency. Furthermore, stunting and thinness were also related to micronutrient deficiencies.
Transparency Enhances Positive Perceptions of Social Artificial Intelligence
Authors: Xu Ying , Bradford Nora , Garg Radhika
Published: September 2023

Social chatbots are aimed at building emotional bonds with users, and thus it is particularly important to design these technologies so as to elicit positive perceptions from users. In the current study, we investigate the impacts that transparent explanations of chatbots’ mechanisms have on users’ perceptions of the chatbots. A total of 914 participants were recruited from Amazon Mechanical Turk. They were randomly assigned to observe conversations between a hypothetical chatbot and a user in one of the two-by-two experimental conditions: whether the participants received an explanation about how the chatbot was trained and whether the chatbot was framed as an intelligent entity or a machine. A fifth group, who believed they were observing interactions between two humans, served as a control. Analyses of participants’ responses to the postobservation survey indicated that transparency positively affected perceptions of social chatbots by leading users to (1) find the chatbot less creepy, (2) feel greater affinity to the chatbot, and (3) perceive the chatbot as more socially intelligent, though these effects were small. Moreover, transparency appeared to have a larger effect on increasing the perceived social intelligence among participants with lower prior AI knowledge. These findings have implications for the design of future social chatbots and support the addition of transparency and explanation for chatbot users.
The Antimicrobial Peptide LL‐37 as a Predictor Biomarker for Periodontitis with the Presence and Absence of Smoking: A Case‐Control Study
Authors: Kzar Wael Abdulazeez , Abbas Raghad Fadhil , Hussein Hashim Mueen
Published: September 2023

Background. A major issue is finding a valid biomarker able to diagnose periodontal disease with the presence and absence of risk factors. Indeed, the association between smoking and periodontal diseases and its impact on the manifestation of antimicrobial peptides has been delineated in clinical and epidemiological investigations. The antimicrobial peptide cathelicidin (LL‐37) is pivotal in preserving periodontal health. Objectives. This investigation examines and contrasts the levels of cathelicidin in the saliva of smokers and nonsmokers of periodontitis. The study also seeks to establish this biomarker’s diagnostic ability to differentiate between periodontal health and disease. Materials and Methods. The study involved the collection of unstimulated saliva samples from 160 participants, comprising 80 patients diagnosed with periodontitis (40 of whom were smokers and 40 were nonsmokers) and 80 periodontitis‐free individuals (40 smokers and 40 nonsmokers). The clinical periodontal parameters were assessed, including recording the probing pocket depth, the level of clinical attachment, and the percentage of bleeding on probing. Subsequently, enzyme‐linked immunosorbent assays were conducted to quantify the protein levels of LL‐37 in the saliva samples obtained from the subjects mentioned above. Results. The highest level of salivary LL‐37 was found in the nonsmoker periodontitis (NSP) patients, followed by the group of smoker periodontitis (SP) and then nonsmoker healthy (NSH) group, while the lowest level was found in the healthy smoker (HS) group. At the same time, the LL‐37 seems to be a very good biomarker in differentiating periodontal health from disease with the presence and absence of smoking. Conclusion. Periodontitis results in a significant elevation of salivary LL‐37 levels in smoker and nonsmoker patients compared to healthy individuals. These levels are positively correlated with the periodontal parameter and can serve as a valuable diagnostic tool to predict periodontitis, whereas smoking significantly reduces these levels.
Adsorption-Reduction Behavior of Cr(VI) by Ferrihydrite-Fulvic Acid Complexes with Different C/Fe Mole Ratios
Authors: Zhang Yangyang , Chen Yuxin , An Junwen , Zhao Xiaofei , Zu Bo
Published: September 2023

Ferrihydrite and fulvic acid are prevalent components of soils and can significantly influence the environmental behavior of Cr(VI) in these matrices. Prior research has investigated the sorption behavior of Cr(VI) by ferrihydrite and fulvic acid independently; however, the sorption-reduction capacity of Cr(VI) by the ferrihydrite-fulvic acid complex, which is ubiquitously present in soils, has been less explored. In this study, ferrihydrite-fulvic acid complexes (Fh-FA) with varying C/Fe mole ratios were synthesized, and the adsorption-reduction behaviors of Cr(VI) on Fh-FA were examined using batch experiments, FTIR, BET, XRD, SEM-EDS, and XPS. The results demonstrate that the pseudo-second-order kinetic model can accurately describe the adsorption process of Fh-FA on Cr(VI), which can be delineated into three stages: rapid adsorption (0-30 min), slow adsorption (30-120 min), and reaction equilibrium (>120 min). The adsorption of Cr(VI) on Fh-FA primarily occurs through chemisorption. FTIR and XPS analyses revealed that Cr(VI) is initially adsorbed by Fe-OH on the Fh-FA surface. However, as the C/Fe mole ratio of Fh-FA increases, more Fe-OH is complexed by -COOH from FA, resulting in a decrease in the adsorption capacity of Cr(VI) by Fh-FA. The number of phenolic hydroxyl groups from FA also increases, providing additional electrons to reduce Cr(VI) to Cr(III) with increasing C/Fe mole ratio. This study not only emphasizes the adsorption-reduction behavior of Cr(VI) by ferrihydrite-fulvic acid complexes but also uncovers the interplay between C/Fe mole ratios and Cr(VI) adsorption-reduction, contributing to a more comprehensive understanding of the relative roles of Fe hydroxides and natural organic matter in soil environments. These findings have significant implications for Cr(VI) management in soils, enhancing our capability to protect and sustain the environmental quality.
The UCMD-Causing COL6A1 (
c
.
930
+
189
C
>
T
) Intron Mutation Leads to the Secretion and Aggregation of Single Mutated Collagen VI α1 Chains
Authors: Freiburg Carolin D. , Solomon-Degefa Herimela , Freiburg Patrick , Mörgelin Matthias , Bolduc Véronique , Schmitz Sebastian , Ala Pierpaolo , Muntoni Francesco , Behrmann Elmar , Bönnemann Carsten G. , Schiavinato Alvise , Paulsson Mats , Wagener Raimund
Published: September 2023

Collagen VI is a unique member of the collagen family. Its assembly is a complex multistep process and the vulnerability of the process is manifested in muscular diseases. Mutations in COL6A1, COL6A2, and COL6A3 lead to the severe Ullrich Congenital Muscular Dystrophy (UCMD) and a spectrum of disease of varying severity including the milder Bethlem muscular dystrophy. The recently identified dominant intronic mutation in COL6A1 (

c
.
930
+
189
C
>
T

) leads to the partial in-frame insertion of a pseudoexon between exon 11 and exon 12. The pseudoexon is translated into 24 amino acid residues in the N-terminal region of the triple helix and results in the interruption of the typical G-X-Y motif. This recurrent de novo mutation leads to UCMD with a severe progression within the first decade of life. Here, we demonstrate that a mutation-specific antibody detects the mutant chain colocalizing with wild type collagen VI in the endomysium in patient muscle. Surprisingly, in the cell culture of patient dermal fibroblasts, the mutant chain is secreted as a single α chain, while in parallel, normal collagen VI tetramers are assembled with the wild-type α1 chain. The mutant chain cannot be incorporated into collagen VI tetramers but forms large aggregates in the extracellular matrix that may retain the ability to interact with collagen VI and potentially with other molecules. Also, α1 chain-deficient WI-26 VA4 cells transfected with the mutant α1 chain do not assemble collagen VI tetramers but, instead, form aggregates. Interestingly, both the wild type and the mutant single α1 chains form amorphous aggregates when expressed in HEK293 cells in the absence of α2 and α3 chains. The detection of aggregated, assembly incompetent, mutant collagen VI α1 chains provides novel insights into the disease pathophysiology of UCMD patients with the COL6A1 (

c
.
930
+
189
C
>
T

) mutation.
Cryptocurrency Adoption among Saudi Arabian Public University Students: Dual Structural Equation Modelling and Artificial Neural Network Approach
Authors: Alomari Ali S. A. , Abdullah Nasuha L.
Published: September 2023

Cryptocurrency is receiving widespread acceptance in the international market. Unfortunately, little attention is focused on the full identification of the cryptocurrency adoption factors, especially when it comes to emerging nations like Saudi Arabia. The current investigation is aimed at investigating whether the use of dual structural equation modelling and artificial neural network (SEM-ANN) would permit a better comprehension of the determinants of cryptocurrency adoption than the single-step PLS-SEM technique and explore the predictors of cryptocurrency adoption. An extended unified theory of acceptance and use of technology (UTAUT) model was used. A sample of 344 responses from Saudi Arabian students at public universities was used to verify the model. Unlike the majority of existing studies that were based on a single-step PLS-SEM approach, this investigation employed a superior statistical approach, the dual SEM-ANN approach, considered a unique methodological approach that can recognise variables’ connections that are both linear and nonlinear and predict relationships with higher accuracy. Moreover, the dual SEM-ANN analysis revealed security as the most important factor influencing whether users would accept cryptocurrency, followed by effort expectancy and awareness. The application of the dual SEM-ANN technique and the extension of the UTAUT model with security and awareness constructs have enhanced the existing technology adoption literature. Additionally, methodological, theoretical, and practical contributions were offered by this study.
Data from Targeting Upregulated cIAP2 in SOX10-Deficient Drug Tolerant Melanoma
Authors: Glasheen McKenna Q. , Caksa Signe , Young Amelia G. , Wilski Nicole A. , Ott Connor A. , Chervoneva Inna , Flaherty Keith T. , Herlyn Meenhard , Xu Xiaowei , Aplin Andrew E. , Capparelli Claudia
Published: September 2023

Abstract
Drug tolerance and minimal residual disease (MRD) are likely to prelude acquired resistance to targeted therapy. Mechanisms that allow persister cells to survive in the presence of targeted therapy are being characterized but selective vulnerabilities for these subpopulations remain uncertain. We identified cellular inhibitor of apoptosis protein 2 (cIAP2) as being highly expressed in SOX10-deficient drug tolerant persister (DTP) melanoma cells. Here, we show that cIAP2 is sufficient to induce tolerance to MEK inhibitors, likely by decreasing the levels of cell death. Mechanistically, cIAP2 is upregulated at the transcript level in SOX10-deficient cells and the AP-1 complex protein, JUND, is required for its expression. Using a patient-derived xenograft model, we demonstrate that treatment with the cIAP1/2 inhibitor, birinapant, during the MRD phase delays the onset of resistance to BRAF inhibitor and MEK inhibitor combination therapy. Together, our data suggest that cIAP2 upregulation in SOX10-deficient subpopulations of melanoma cells induces drug tolerance to MAPK targeting agents and provides a rationale to test a novel therapeutical approach to target MRD.
Data from AMT-562, a novel HER3-targeting antibody drug conjugate, demonstrates a potential to broaden therapeutic opportunities for HER3-expressing tumors
Authors: Weng Weining , Meng Tao , Pu Junyi , Ma Linjie , Shen Yi , Wang Zhaohui , Pan Rong , Wang Mingqiao , Chen Caiwei , Wang Lijun , Zhang Jianjian , Zhou Biao , Shao Siyuan , Qian Yu , Liu Shu-Hui , Hu Wenhao , Meng Xun
Published: September 2023

Abstract
HER3 is a unique member of the epidermal growth factor receptor family of tyrosine kinases, which is broadly expressed in several cancers, including breast, lung, pancreatic, colorectal, gastric, prostate, and bladder cancers and is often associated with poor patient outcomes and therapeutic resistance. U3-1402/Patritumab-GGFG-DXd is the first successful HER3-targeting ADC molecule with clinical efficacy in non-small cell lung cancer (NSCLC). However, over 60% of patients are non-responsive to U3-1402 due to low target expression levels and responses tend to be in patients with higher target expression levels. U3-1402 is also ineffective in more challenging tumor types such as colorectal cancer. AMT-562 was generated by a novel anti-HER3 antibody Ab562 and a modified self-immolative PABC spacer (T800) to conjugate exatecan. Exatecan showed higher cytotoxic potency than its derivative DXd. Ab562 was selected due to its moderate affinity for minimizing potential toxicity and improving tumor penetration purposes. Both alone or in combination therapies, AMT-562 showed potent and durable antitumor response in low HER3 expression xenograft and heterogeneous patient-derived xenograft/organoid (PDX/PDO) models, including digestive system and lung tumors representing of unmet needs. Combination therapies pairing AMT-562 with therapeutic antibodies, inhibitors of CHEK1, KRAS and TKI showed higher synergistic efficacy than Patritumab-GGFG-DXd. Pharmacokinetics and safety profiles of AMT-562 were favorable and the highest dose lacking severe toxicity was 30 mg/kg in cynomolgus monkeys. AMT-562 has potential to be a superior HER3-targeting ADC with a higher therapeutic window that can overcome resistance to generate higher percentage and more durable responses in U3-1402-insensitive tumors.
So Grateful for My X: Sex Chromosomes Drive Differences in Glioblastoma Immunity
Authors: Alspach Elise
Published: September 2023

Males are at a greater risk of developing glioblastoma and face poorer prognoses compared with their female counterparts for reasons that are not well understood. Lee and colleagues uncover a role for sex-based differences in CD8+ T-cell function, which adds another layer to our growing understanding that antitumor immunity is not generated equivalently between males and females.

See related article by Lee et al., p. 2090 (5).
Express Delivery of Next-Generation CAR T Cells with Preserved Naive and Stemness Phenotypes for the Treatment of Aggressive Lymphomas
Authors: Wang Michael
Published: September 2023

In this issue of Cancer Discovery, Dickinson and colleagues present clinical data from a first-in-human study of YTB323, a novel autologous CD19-directed chimeric antigen receptor T-cell therapy generated on the T-Charge platform with preserved naive state and stemness phenotypes. Treatment with YTB323 achieved high overall response rates, durable complete remissions, and good overall safety. Their cell doses are up to 25-fold lower than with tisagenlecleucel.

See related article by Dickinson et al., p. 1982 (10).
Challenges and Opportunities in Building a Global Representative Single-Cell and Spatial Atlas in Cancer
Authors: Plummer Jasmine T. , George Sophia H.L.
Published: September 2023

Cancer health disparities are complex and a mixture of factors that need to be accounted for in both our planning, implementation, and execution across all researchers, especially in single-cell and spatial technologies, which have a higher burden for adoption in low- and middle-income countries. This commentary tackles the hurdles these technologies face in creating a diverse, representative atlas of cancer and is a call to arms for a strategic plan toward inclusivity across all global populations.
A Critical Analysis of the Philippine Construction Industry: Current Trends, Forecast, and Business Focus for Engineering Design Firms
Authors: Siman Bennegreg Pamplona
Published: September 2023

The construction industry in the Philippines plays a vital role in the country's economic growth, infrastructure development, and job creation. The construction industry continues to be one of the predominant drivers of Philippines' economic progress. In 2022, an annual growth rate of 9.2% was obtained by the Philippine construction industry and continues to escalate brought by the flagship project of the former President Rodrigo Duterte, Build! Build! Build! Program (BBB). The current government plans to modernize the country’s infrastructure backbone, increasing construction jobs to maintain rapid growth, captivate investments and expand economic opportunities for all Filipinos. It is globally known that the construction industry regularly consumes more raw materials, resulting in scarcity with our natural resources and produced environmental implications. Therefore, the current engineering and construction industry moves towards green construction and buildings. The Philippine government has been actively promoting infrastructure development as a key driver of economic growth. The country will be the fastest growing construction market with an estimated six percent growth per annum, over the next 15 years. This study provided information on the current trends in the Philippine construction industry, forecasts its trajectory over the next five years, and highlights the necessary business focus for engineering design firms. Information obtained from the literature, project documents, memos, reports, and other data available served as primary inputs for discussion and basis for conclusions and recommendations.
Development and Validation of an Interactive E-Book in Physics 9
Authors: Dominado Noel , Bulaun Criselle May P. , Quiambao Cynthia G.
Published: September 2023

The study developed and validated an interactive e-book in Physics in Grade 9 Science to help augment the learning gaps and the least mastered competencies based on the regional diagnostic assessment. The content of the lessons in the interactive e-book was based on the six (6) least learned, most essential learning competencies that were provided by the Department of Education. The material was conceptualized based on objectives, content or parts, and evaluation tools. The developed interactive e-book was validated in terms of content quality, instructional quality, technical quality, and other findings. Based on the results of the validation of the six (6) faculty experts, it revealed that the crafted material was very satisfactory in all the criteria, which means that it was valid and ready for use by the students. The learners evaluated the developed material in terms of content, adequacy of scope, and appropriateness of exercises. It inferred that the interactive e-book was acceptable and reliable for its intended users. The result of this study has a significant implication to teaching Physics to Grade 9 students. It means that the material can serve as supplementary material since the students were engaged in learning and had shown interest when the lesson involved educational technology, and since there are insufficient modern instructional materials in Physics.