bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental and finite element assessment of stabilizing configurations for underground heritage sites
Authors: Hemeda Sayed
Published: August 2024

Heritage sites in Alexandria, Egypt, are some of the UNESCO world heritage sites at high risk from geo-environmental hazards, in particular caused by sea level rise and heavy rain due to the climate change. Recently, safeguarding UNESCO world subterranean and built heritage draws more attention. After recent environmental catastrophies in Alexandria, sustainable conservation materials and stabilizing configurations of underground monumental structures has also become urgent and highly demanded. Based on typical damage due to the heavy weathering caused by the ground water table and salt, this paper offers a guide for engineers and conservators, where rock structures consolidation and stabilizing configurations to protect these structures in the static state and against strong seismic events is presented. In this paper, typical geotechnical problems and damage to the Catacombs of of Kom El-Shoqafa are presented first, followed by an experimental evaluation methodology that includes spectroscopic and morphological characterization in addition to the mechanical testing of untreated and treated rock samples with synthetic organosilicone and acrylic compounds. The effectiveness of the new silica-based consolidants was evaluated in terms of the amount of solid adsorbed, mechanical properties (e.g., surface hardness, ultrasonic velocity, modulus of elasticity and modulus of compressive strength), and resistance to salt crystallization. The treated groups showed better mechanical strength than the control group. The ability of the treated samples to resist climate change negative impact was also greatly improved. According to laboratory tests, new silica-based hardeners and hydrophobic materials have great potential for strengthening weathered Calcarenitic rock structures. It was observed that the rock samples containing the modified binder (MTMOS + Wacher BS 15) reach higher mechanical strength parameters. After the experimental study (testing procedures), FEM analysis was performed using PLAXIS 2D code to validate the silica-based consolidants and verify their efficiency in improving the response of rock structures in static and seismic states against strong earthquake events. The results of this work confirm the high potential of low-cost injection techniques and stabilizing configurations (pre- stressed anchors and concrete friction piles) technology, confirming the possibility of achieving significant improvement in the geotechnical properties of Calcarenitic rock structures and enhancing the seismic performance of underground archaeological structures using low-cost injection technology that is easy to manufacture.
Congenital hydrocephalus: a review of recent advances in genetic etiology and molecular mechanisms
Authors: Liu Xiu-Yun , Song Xin , Czosnyka Marek , Robba Chiara , Czosnyka Zofia , Summers Jennifer Lee , Yu Hui-Jie , Gao Guo-Yi , Smielewski Peter , Guo Fang , Pang Mei-Jun , Ming Dong
Published: August 2024

The global prevalence rate for congenital hydrocephalus (CH) is approximately one out of every five hundred births with multifaceted predisposing factors at play. Genetic influences stand as a major contributor to CH pathogenesis, and epidemiological evidence suggests their involvement in up to 40% of all cases observed globally. Knowledge about an individual’s genetic susceptibility can significantly improve prognostic precision while aiding clinical decision-making processes. However, the precise genetic etiology has only been pinpointed in fewer than 5% of human instances. More occurrences of CH cases are required for comprehensive gene sequencing aimed at uncovering additional potential genetic loci. A deeper comprehension of its underlying genetics may offer invaluable insights into the molecular and cellular basis of this brain disorder. This review provides a summary of pertinent genes identified through gene sequencing technologies in humans, in addition to the 4 genes currently associated with CH (two X-linked genes L1CAM and AP1S2, two autosomal recessive MPDZ and CCDC88C). Others predominantly participate in aqueduct abnormalities, ciliary movement, and nervous system development. The prospective CH-related genes revealed through animal model gene-editing techniques are further outlined, focusing mainly on 4 pathways, namely cilia synthesis and movement, ion channels and transportation, Reissner’s fiber (RF) synthesis, cell apoptosis, and neurogenesis. Notably, the proper functioning of motile cilia provides significant impulsion for cerebrospinal fluid (CSF) circulation within the brain ventricles while mutations in cilia-related genes constitute a primary cause underlying this condition. So far, only a limited number of CH-associated genes have been identified in humans. The integration of genotype and phenotype for disease diagnosis represents a new trend in the medical field. Animal models provide insights into the pathogenesis of CH and contribute to our understanding of its association with related complications, such as renal cysts, scoliosis, and cardiomyopathy, as these genes may also play a role in the development of these diseases. Genes discovered in animals present potential targets for new treatments but require further validation through future human studies.
Multiple-biomarker approach in the assessment of bisphenol A effect on the grooved carpet clam Ruditapes decussatus (Linnaeus, 1758)
Authors: Nour Ola Mohamed , El-Saidy Salwa A. , Ghoneim Aml Z.
Published: August 2024

Background

Bisphenol A (BPA), a plastic additive monomer, is among the most highly produced chemicals worldwide, and is broadly used in many industries, such as food and beverage containers, milk bottles, and paper products. Previous studies demonstrated that BPA has potential toxicity to aquatic organisms, causing endocrine disturbance and behavioural disorders. The current work aimed to determine the toxic impacts of BPA on the edible marine clam Ruditapes decussatus considering a multi-biomarker approach (mortality, biochemical studies, DNA strand breaks using comet assay, and histopathological examinations with semi-quantitative and quantitative histopathological analyses). The clams were exposed under laboratory conditions to three concentrations of BPA (0 “control”, 1, and 5 µg/L) for a period of 21 days. After the exposure period, BPA impacts were assessed in the digestive gland as a versatile and environmentally relevant organ for ecotoxicological studies.

Results

In BPA-treated clams, mortality (10%) occurred only at the highest BPA concentration (5 µg/L). Biochemical impairments were detected in a concentration-dependent manner as a consequence of BPA exposure. There were significant increases in malondialdehyde (MDA) and glutathione (GSH) levels, while catalase (CAT) activity was significantly reduced. Our results revealed that BPA induced neurotoxicity in R. decussatus, as evidenced by the inhibition of acetylcholinesterase (AChE) activity in a dose-dependent manner. Furthermore, DNA damage was strongly induced as BPA levels increased. Additionally, our results have been affirmed by alterations in digestive gland tissues at BPA treatments, which consequently can impair the clam’s ability for food absorption; these alterations included mainly atrophic and necrotic digestive tubules, epithelial cell vacuolization, hemocyte infiltration, and intertubular fibrosis. Based on the data obtained from the semi-quantitative and quantitative histopathological analyses, the exposure of the clam’s digestive gland to BPA with concentrations of 1 and 5 µg/L for 21 days showed significant histopathological alterations compared with the control clams.

Conclusion

The multi-biomarker approach used in the current study proved to be a useful tool for assessing the impact of diphenylmethane compounds, such as BPA. Water-borne BPA causes oxidative stress, neurotoxicity, genotoxicity, and deleterious effects on the clam digestive gland; all of these could deteriorate clam performance and health, causing tissue dysfunction.
The Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue) scale in patients with axial spondyloarthritis: psychometric properties and clinically meaningful thresholds for interpretation
Authors: Cella David , de la Loge Christine , Fofana Fatoumata , Guo Shien , Ellis Alicia , Fleurinck Carmen , Massow Ute , Dougados Maxime , Navarro-Compán Victoria , Walsh Jessica A.
Published: August 2024

Background

Fatigue is an important symptom for most patients with axial spondyloarthritis (axSpA). The FACIT-Fatigue is a 13-item patient-reported outcome (PRO) instrument that has been used in axSpA clinical trials to measure fatigue severity and impact on daily activities. However, the psychometric properties of the FACIT-Fatigue are not fully evaluated across the entire spectrum of axSpA including non-radiographic axSpA (nr-axSpA) and radiographic axSpA (r-axSpA). This study determined: (1) the psychometric properties of the FACIT-Fatigue in nr-axSpA, r-axSpA, and the broad axSpA population and (2) FACIT-Fatigue scores representing meaningful within-patient change (MWPC), meaningful between-group differences, and cross-sectional severity bands.

Methods

Data from two Phase 3 trials in adults with nr-axSpA (BE MOBILE 1; N = 254) and r-axSpA (BE MOBILE 2; N = 332) were analyzed pooled and separately to assess the psychometric properties of the FACIT-Fatigue. MWPC and meaningful between-group difference estimates were derived using anchor-based and distribution-based methods. Cross-sectional fatigue severity bands were estimated using logistic regression analysis.

Results

The FACIT-Fatigue presented good internal consistency, adequate convergent and known-groups validity, and was sensitive to change over time across the full axSpA spectrum. A 5–11-point increase in FACIT-Fatigue score was estimated to represent a MWPC, with an 8-point increase selected as the responder definition. A 2.14–5.34-point difference in FACIT-Fatigue score change over a 16-week period was estimated to represent a small-to-medium meaningful between-group difference. FACIT-Fatigue score severity bands were defined as: none or minimal (>40), mild (>30 to ≤40), moderate (>21 to ≤30), and severe (≤21).

Conclusions

These findings support the use of the FACIT-Fatigue as a fit-for-purpose measure to assess fatigue-related treatment benefit in axSpA clinical trials. The proposed score estimates and thresholds can guide FACIT-Fatigue score interpretation across the full axSpA spectrum.

Trial registration

ClinicalTrials.Gov, NCT03928704. Registered 26 April 2019—Retrospectively registered, https://classic.clinicaltrials.gov/ct2/show/NCT03928704. ClinicalTrials.Gov, NCT03928743. Registered 26 April 2019—Retrospectively registered, https://classic.clinicaltrials.gov/ct2/show/NCT03928743.
Transitioning between the EQ-5D youth and adult descriptive systems in a group of adolescents
Authors: Verstraete Janine , Kind Paul , Janssen Mathieu F. , Yang Zhihao , Stolk Elly , Gebregziabiher Abraham
Published: August 2024

Purpose

To investigate whether the same health state results in the same distribution of responses on the EQ-5D youth and adult descriptive systems.

Methods

Adolescents aged 13–18 years with a range of health conditions and from the general school going population were recruited in South Africa (ZA) and Ethiopia (ET). In ZA participants completed the English EQ-5D-3L, EQ-5D-Y-3L and EQ-5D-5L in parallel. Whereas in ET participants completed the Amharic EQ-5D-5L and EQ-5D-Y-5L in parallel. Analysis aimed to describe the transition between youth and adult instruments and not differences between countries.

Results

Data from 592 adolescents completing the EQ-5D-3L, EQ-5D-Y-3L and EQ-5D-5L (ZA) and 693 completing the EQ-5D-5L and EQ-5D-Y-5L (ET) were analysed. Adolescents reported more problems on the youth versions compared to the adult version for the dimension of mental health. 13% and 4% of adolescents who reported no problems on the EQ-5D-3L and EQ-5D-5L reported some problems on the EQ-5D-Y-3L respectively. This was less notable with transition between the five level versions with 4% of adolescents reporting more problems on the EQ-5D-Y-5L than the EQ-5D-5L. Very few adolescents reported severe problems (level 3 on the EQ-5D-3L or EQ-5D-Y-3L and level 4 and level 5 on the EQ-5D-5L or EQ-5D-5L) thus there was little variation between responses between the versions. In ZA, discriminatory power, measured on the Shannon’s Index, was higher for Y-3L compared to 3L for pain/discomfort (ΔH′=0.11) and anxiety/depression (ΔH′=0.04) and across all dimensions for Y-3L compared to 5L. Similarly, in ET discriminatory power was higher for Y-5L than 5L (ΔH′ range 0.05–0.09). Gwet’s AC showed good to very good agreement across all paired (ZA) 3L and (ET) 5L dimensions. The summary score of all EQ-5D versions were able to differentiate between known disease groups.

Conclusion

Despite the overall high levels of agreement between EQ-5D instruments for youth and for adults, they do not provide identical results in terms of health state, from the same respondent. The differences were most notable for anxiety/depression. These differences in the way individuals respond to the various descriptive systems need to be taken into consideration for descriptive analysis, when transitioning between instruments, and when comparing preference-weighted scores.
A person-reported cumulative social risk measure does not show bias by income and education
Authors: Jones Salene M.W. , Briant Katherine J. , Doody David R. , Iachan Ronaldo , Mendoza Jason A.
Published: August 2024

Background

Social risk such as housing instability, trouble affording medical care and food insecurity are a downstream effect of social determinants of health (SDOHs) and are frequently associated with worse health. SDOHs include experiences of racism, sexism and other discrimination as well as differences in income and education. The collective effects of each social risk a person reports are called cumulative social risk. Cumulative social risk has traditionally been measured through counts or sum scores that treat each social risk as equivalent. We have proposed to use item response theory (IRT) as an alternative measure of person-reported cumulative social risk as IRT accounts for the severity in each risk and allows for more efficient screening with computerized adaptive testing.

Methods

We conducted a differential item functioning (DIF) analysis comparing IRT-based person-reported cumulative social risk scores by income and education in a population-based sample (n = 2122). Six social risk items were analyzed using the two-parameter logistic model and graded response model.

Results

Analyses showed no DIF on an IRT-based cumulative social risk score by education level for the six items examined. Statistically significant DIF was found on three items by income level but the ultimate effect on the scores was negligible.

Conclusions

Results suggest an IRT-based cumulative social risk score is not biased by education and income level and can be used for comparisons between groups. An IRT-based cumulative social risk score will be useful for combining datasets to examine policy factors affecting social risk and for more efficient screening of patients for social risk using computerized adaptive testing.
Health-related quality of life in patients with neovascular age-related macular degeneration: a prospective cohort study
Authors: Kubin Anna-Maria , Korva-Gurung Ida , Ohtonen Pasi , Hautala Nina
Published: August 2024

Background

Neovascular age-related macular degeneration (nAMD) is a common cause of visual impairment and blindness in the elderly with globally increasing prevalence. Vascular endothelial growth factor inhibitor (anti-VEGF) treatment has improved visual prognosis of nAMD, but continuous treatment may cause anxiety and stress, although increase in visual acuity (VA) may also have positive effects on patients’ quality of life. The health care burden due to frequent treatment and monitoring is apparent, but the effect of anti-VEGF treatment on patients’ quality of life is not fully understood. We evaluated the overall impact of nAMD and its treatment on newly diagnosed patients’ health-related quality of life (HRQoL) in real-world setting.

Methods

The present prospective cohort study included newly diagnosed nAMD patients treated with anti-VEGF injections at Oulu University Hospital during 2019–2020. Data included parameters from comprehensive ophthalmic examination and fundus imaging, age at diagnosis, sex, comorbidities, visual acuity, and frequency of anti-VEGF injections. HRQoL was assessed by 15D questionnaire at diagnosis, 6 months, and 12 months.

Results

95 nAMD patients were included. They were 78 ± 8 years old, 56 (59%) were female, and 74 (78%) had more than one comorbidity. The patients received 8 ± 3 anti-VEGF-injections. Visual acuity (VA) improved from 56 ± 18 to 61 ± 24 Early treatment diabetic retinopathy study (ETDRS) letters in 12 months. VA improved > 5 ETDRS letters in 45 (47%), remained stable in 30 (32%) and decreased > 5 letters in 17 (18%) eyes. The mean total 15D score reflecting overall HRQoL decreased from 0.850 ± 0.104 to 0.834 ± 0.103 in 12 months. Decreased HRQoL was associated with baseline best-corrected VA (BCVA) ≥ 70 ETDRS letters (p = 0.023) and more than one comorbidity (p = 0.034). HRQoL regarding visual function increased from 0.765 ± 0.194 to 0.789 ± 0.184 during the 12-month follow-up.

Conclusions

In real world setting, HRQoL regarding visual function improved in anti-VEGF-treated nAMD patients during the first 12 months after the diagnosis and treatment initiation. Good baseline VA or several comorbidities were associated with decreased overall HRQoL during the follow-up. Despite the effectiveness of anti-VEGF treatment on visual function, several other aspects affecting elderly patients’ everyday life should be considered when nAMD treatment is implemented.
Sarcoidosis: a general overview
Authors: Neves Fabricio Souza , Pereira Ivanio Alves , Sztajnbok Flavio , Neto Nilton Salles Rosa
Published: August 2024

Sarcoidosis is a systemic inflammatory disease of unknown origin, which consists of the formation of multiple sterile noncaseating granulomas. Inhaled antigens are believed to initiate disease in prone individuals, considering that almost all patients present pulmonary or mediastinal lymph node disease. Extrapulmonary manifestations are common and diverse: practically any organ system can be affected, and treatment can range from simple watchful waiting to intense immunosuppression. In this article, we review current concepts about sarcoidosis in an overview, focusing on recognition and treatment of its major clinical phenotypes.
Impact of body mass index on the relationship of Epicardial fat volume to coronary artery disease in males
Authors: Elkareem Taher said Abd , Elhady Fatma , Ali Asmaa Ahmed
Published: August 2024

Background

Epicardial fat tissue refers to a type of visceral fat tissue that envelops the myocardial and visceral pericardium. It is recognized as a novel risk sign for cardiovascular issues, including coronary artery disease, our aim to assess the influence of body mass index on the amount of epicardial fat volume and its association with coronary artery disease in male patients.

Methods

Epicardial fat volume was quantified using cardiac Computed tomography scans in a cohort of 119 male patients who were believed to have coronary artery disease. Patients were categorized into three groups based on their body mass index values: Group I Body Mass Index (BMI ≥ 18.5–24.9 kg/m2), Group II (BMI ≥ 25–29.9 kg/m2), and Group III (BMI ≥ 30 kg/m2).

Results

In Group I, there were twenty-three patients (19.3%) with a mean epicardial fat volume of 40 ± .42.8 ml. In Group II, there were forty-three patients (36%) with a mean  Epicardial Fat Volume (EFV) of 56 ± 21.5 ml. In Group III, there were 53 patients (44%) with a mean EFV of 56 ± 15.8 ml, when compared to the results of Group I, which were considerably higher (p = 0.0004). Regarding prevalence of obstructive coronary artery disease in our patient population, 86 individuals (72.3%) were diagnosed with obstructive coronary artery disease and exhibited a tendency to have a greater value of epicardial fat volume at 56.4 ± 18.9 ml, with a range of 19–121 ml, compared to those without coronary artery disease at 45.2 ± 6.7 ml, with a range of 33–55 ml (P < 0.02). The prevalence of coronary artery disease was 85% in group III and 87% in group II. Patients in group III with coronary artery disease exhibited a substantially higher EFV of 46 ± 6.63 vs 16 ± 3.2 ml (p = 0.001) compared to those without obstructive coronary artery disease.

Conclusions

Although epicardial fat volume was elevated in patients with coronary artery disease independent of their BMI, the predictive ability of epicardial fat volume for coronary artery disease was more pronounced in individuals with a body mass index more than 25 kg/m2.
Egyptian car plate recognition based on YOLOv8, Easy-OCR, and CNN
Authors: Sarhan Amany , Abdel-Rahem Rowyda , Darwish Bassel , Abou-Attia Arwa , Sneed Ahmed , Hatem Shahd , Badran Awatef , Ramadan Mohamed
Published: August 2024

This research presents an innovative approach to Egyptian car plate recognition using YOLOv8 and optical character recognition (OCR) technologies. Leveraging the powerful object detection capabilities of YOLOv8, the system efficiently detects car plates within images, videos, or real-time. Subsequently, OCR algorithms are applied to extract alphanumeric characters from the identified plates, facilitating accurate license plate recognition. The integration of YOLOv8 and OCR enhances the system's robustness in varying conditions, contributing to improved performance in real-world scenarios. This study advances the field of automatic license plate recognition, showcasing the potential for practical applications in traffic management, law enforcement, and security systems. A public dataset of Egyptian car plates is used for training and testing the model. Two OCR approaches are used and tested which proved their performance, while CNN-based approach reaches 99.4% accuracy.
Assessing homogeneous and heterogeneous economic impacts of fall armyworm management practices on farm performance in Ghana
Authors: Kondo Ebenezer , Osae Michael Yao , Owusu Victor
Published: August 2024

One of the emerging challenges impinging on sustainable food production in sub-Saharan Africa is the invasion of the fall armyworm (FAW) pest. Data collected from farm households in different agro-ecological zones in Ghana and a Multivalued Treatment Effect (MVTE) model were used to argue that FAW management practices are key to stemming the debilitating effects of FAW infestations on farm performance. Previous studies have analysed homogeneous treatment effects to explain FAW management practices. The present study employs heterogeneous treatment effects to account for the differential effects of FAW management practices such as early planting, application of prescribed pesticides, and a combination of both practices while accounting for socioeconomic characteristics. Findings from the study reveal that distance to extension services exerts negative effects on adoption of early planting only, and adoption of both FAW management practices. Moreover, past FAW infestations tend to exert a positive effect on adoption of pesticide application only and adoption of a combination of the FAW management practices. Adopting the FAW management practices examined in this study assisted the maize producers in raising their farm performance. Socioeconomic characteristics also tend to influence the homogeneous treatment effects of adoption of the FAW management practices on farm performance. This finding indicates that heterogeneity within farm households is crucial for policy regarding adoption of FAW management practices.
Patient-reported outcomes (PROs) from a randomized, phase 3 trial of enfortumab vedotin plus pembrolizumab (EV+P) versus platinum-based chemotherapy (PBC) in previously untreated locally advanced or metastatic urothelial cancer (la/mUC).
Authors: Kikuchi Eiji , Gupta Shilpa , Loriot Yohann , Van Der Heijden Michiel Simon , Bedke Jens , Valderrama Begoña Pérez , Flechon Aude , Petrylak Daniel P. , De Santis Maria , Galsky Matt D. , Lee Jae Lyun , Swami Umang , Sridhar Srikala S. , De Giorgi Ugo , Wright Phoebe , Lu Yi-Tsung , Guan Xuesong , Dillon Ryan , Homet Moreno Blanca , Powles Thomas
Published: August 2024

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Background: EV+P nearly doubled median progression-free survival and overall survival vs PBC in patients (pts) with previously untreated la/mUC in the phase 3 EV-302 trial. PROs are reported here. Methods: In EV-302 (NCT04223856) pts were randomized 1:1 to EV+P or PBC (gemcitabine with cisplatin or carboplatin). PRO assessments included the EORTC Quality of Life Questionnaire (EORTC QLQ-C30), and the Brief Pain Inventory Short Form (BPI-SF) completed at baseline, weekly for 12 weeks (wks), then every 3 wks through survival follow-up, inclusive of the time post-progression. Time to pain progression (TTPP) and mean change from baseline in worst pain at wk 26 using the BPI-SF were prespecified analyses statistically tested using a gatekeeping strategy. Mean change from baseline through wk 26 and time to confirmed deterioration (TTCD) of EORTC-QLQ-C30 and BPI-SF domains were prespecified descriptive analyses. TTPP and TTCD were assessed using Kaplan-Meier methods. Results: Of 886 pts randomized, 731 (376 received EV+P; 355 PBC) completed baseline PRO questionnaires. Compliance rates differed between arms and remained >70% through wk 29 for EV+P and through only wk 17 for PBC. Median TTPP was 14.2 months (mos) with EV+P and 10.0 mos with PBC (hazard ratio [HR]=0.92; 95% CI=0.72, 1.17; 2-sided p-value=0.48). The least squares (LS) mean reduction in worst pain at wk 26 was numerically greater with EV+P vs PBC (-0.61 vs -0.03, LS mean difference [95% CI]: -0.58 [-1.05, -0.11] [nominal 2-sided P = 0.015]). Pts with moderate to severe pain at baseline who were treated with EV+P (n=128, 34%) had a meaningful (>2 pt) improvement from baseline in BPI worst pain from wk 3 through 26. In EORTC QLQ-C30 Global Health Status/Quality of Life [GHS/QoL], EV+P demonstrated a transient worsening at week 3 (-6.3) that returned to baseline from weeks 4 through 26, while patients treated with PBC demonstrated deterioration from week 1 through week 17 (range -1.2 to -7.1) where scores returned to baseline. TTCD for EORTC QLQ-C30 GHS/QoL was 5.9 mos with EV+P vs 3.2 mos with PBC (HR = 0.98 [95% CI]: 0.79 – 1.2). Conclusions: Pts treated with EV+P have improved survival compared with PBC without detriment to quality of life and functioning, further supporting the value of EV+P for pts with la/mUC. Compliance, especially after progression, was lower than expected (particularly in the PBC arm) and may have impacted the results. Clinical trial information: NCT04223856 .
Restriction of YWHAB-mediated YAP cytoplasmic retention as a novel mechanism underlying stemness maintenance and chemo-resistance in peritoneal metastasis of ovarian cancer: A comparative proteomic study.
Authors: Qiu Lin , Liu Chang , Ma Wenxin , Yang Zhuo
Published: August 2024

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Background: Ovarian cancer (OC) peritoneal metastasis (OCPM) is a significant cause of high mortality of OC. To investigate the mechanisms underlying OCPM stemness maintenance and resistance, we characterized proteomic alterations in residual OCPM tissues after neoadjuvant chemotherapy (NACT), and verified restriction of YWHAB-mediated YAP cytoplasmic retention as a novel important mechanism. Methods: Tumor specimens from HGSOC patients underwent proteomic analysis using TMT and REACTOME for pathway and GO analysis. The OVCAR3 cell line, derived from malignant ascites, and formalin-fixed samples were used for Immunohistochemistry. Ovarian cancer stem-like cells, including cisplatin-resistant cells, were cultured, and ALHD activity was measured by qPCR and ALDEFLUOR Kit. Western blot and Co-IP were used for protein analysis. Sphere formation and limiting dilution assays were performed in vitro and in vivo using BALB/c nude mice, and FACS quantified OCSCs. YWHAB-knockdown cells were created via plasmids, lentivirus, and transfection. Statistical tests included paired and unpaired t-tests, one-way ANOVA, and ELDA for limiting dilution. Data are shown as mean ± SD, with *p< 0.05, **p< 0.01, ***p< 0.001 indicating significance. Results: TMT-based proteomics identified 324 differentially expressed proteins in post-NACT OCPM tissues, with 179 upregulated and 145 downregulated. Bioinformatics revealed novel targets in key pathways, including TUBB, VCP in Hedgehog, YWHAB in Hippo, TLA1/2, SPTA1 in MAPK, and FASN in NOTCH. YWHAB downregulation was confirmed in pPR OCPM tissues and cells, serving as a marker to differentiate pNR from pCR/pPR OCPM (AUC = 0.7673). YWHAB inhibition in pCR OCPM cells enhanced stemness, as seen in sphere formation, OCSC percentages, CD133 expression, ALDH activity, and tumorigenicity. It also induced cisplatin resistance. YWHAB inhibition reduced cytoplasmic YAP retention and increased nuclear YAP, enhancing transcriptional activity. YAP5SA expression negated the effects of YWHAB depletion on stemness and resistance in pCR OCPM cells. Conclusions: In summary, this study explored the potential mechanisms underlying OCPM stemness maintenance and resistance by employing proteomic analysis, and revealed a novel YWHAB-mediated mechanism. This finding indicates that YAP would an important target for eradicating YWHAB-restricted OCSCs in OCPM.
Association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and risk of endometrial cancer among US adults: A population-based study.
Authors: Liu Penglin , Kong Wenzhi , Miao Jinwei
Published: August 2024

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Background: Endometrial cancer, as one of the metabolic-related malignancies, is becoming a significant public health concern worldwide. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has emerged as a comprehensive biomarker of various lipid-related metabolic disorders. However, the association of NHHR with endometrial cancer risk remains unclear to date. Therefore, we conducted this nationwide cross-sectional study to investigate the association of NHHR with the risk of endometrial cancer among US adults. Methods: Data were obtained from the National Health and Nutrition Examination Survey (1999–2018). Female participants who provided complete data on the NHHR and endometrial cancer were enrolled. The association of the NHHR with endometrial cancer was assessed by multivariate logistic regression analyses, adjusted by multiple potential confounders. Meanwhile, sensitivity analyses and subgroup analyses were conducted. Results: A total of 25,411 eligible participants were enrolled, including 214 (0.8%) women with endometrial cancer. The fully-adjusted multivariate logistic model showed a significantly positive association of NHHR with the endometrial cancer risk (odds ratio [OR] 1.15, 95% confidence interval [CI]: 1.05–1.25; P=0.003). Comparing the highest to the lowest quartile of NHHR, the fully-adjusted OR was 1.52 (95% CI: 1.02–2.28, P for trend=0.017). In subgroup analyses, the significantly positive association between NHHR and the risk of endometrial cancer was also found in non-obese women (OR 1.18, 95% CI: 1.04–1.35, P=0.012), women without diabetes (OR 1.15, 95% CI: 1.02–1.30, P=0.027), women with hypertension (OR 1.15, 95% CI: 1.03–1.28, P=0.012), women who use oral contraceptives (OR 1.16, 95% CI: 1.04–1.30, P=0.009) and in parous women(OR 1.15, 95% CI: 1.05–1.27, P=0.003). Additionally, in the sensitivity analysis by excluding participants with NHHR below 5% or above 95% in total cohort, the positive association of NHHR with endometrial cancer risk remained significant (OR 1.21, 95% CI: 1.03–1.42, P=0.018). Conclusions: This population-based study found that a higher NHHR correlated with an increased risk of endometrial cancer among the US population. Our findings suggested that NHHR might be a promising tool for the risk assessment of endometrial cancer. Prospective studies are necessary to further verify these findings. [Table: see text]
First implementation of artificial intelligence empowered all-in-one radiotherapy workflow for nasopharyngeal carcinoma.
Authors: Zhou Guan-Qun , Yang Yu-Xian , Yang Xin , Jiang Xiao-Bo , Lin Li , Wang Guang-Yu , Sun Wen-Zhao , Zhang Kang , Li Bing-Huan , Li Hua , Jia Le-Cheng , Wei Zi-Quan , Liu Yan-Fei , Fu Dan-Ning , Tang Jun-Xiang , Zhang Wei , Zhou Jing-Jie , Feng Chi , Huang Xiao-Yan , Sun Ying
Published: August 2024

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Background: To establish an artificial intelligence (AI)-empowered All-In-One (AIO) workflow for providing one-stop radiotherapy to patients with nasopharyngeal carcinoma (NPC), and evaluate its feasibility and performance. Methods: The NPC-specific AIO workflow operates on a CT-integrated linac and integrates AI contouring and AI planning modules. A 3D U-net was employed for contours generation and 3D dose distribution. Knowledge-based planning approach and a protocol-based approach were used for plan optimization. MRI datasets with contours of primary gross tumors, CT datasets with contours of targets and organs at risk, and radiotherapy treatment planning datasets were collected from 877, 139, and 243 patients, respectively, for the training, validation, and testing of AI contouring and planning models. The NPC-specific AIO workflow underwent real-world clinical testing with an end-to-end evaluation involving 120 patients with NPC. The technical characteristics, implementation procedures and performance of AIO workflow were described and evaluated. Results: From March 2022 to October 2023, 120 patients with newly-diagnosed, non-metastatic NPC underwent AIO workflow, and 117 patients completed it in a median time of 23.2 min (range: 16.3 to 45.8 min). Median translation motions were 0.2 mm (CT scan to planning approval) and 0.1 mm (during beam delivery). AI-generated contours required little revision for clinical target volume (CTV1) and organs at risk (OARs), minor revision for cervical lymph nodes (GTVn) and clinical target volume (CTV2), with median Dice similarity coefficients (DSCs) of 0.98 and 0.94, respectively; more revision for GTVp, with a median DSC of 0.84. Of the 117 AI-generated plannings, 108 (92.3%) passed after initial auto-optimization. Volumes receiving ≥ 100% of the prescribed dose for all planning target volumes was ≥ 97.8%. Mean dosimetric parameters met dose constraints for all OARs except the thyroid and submandibulars. One patient died from acute renal failure after 10 fractions of radiotherapy. At week 12 after radiotherapy completion, 115 patients achieved complete response;1 had stable disease. Grade 3-4 acute effects were reported by 54 of 115 patients (36%). Conclusions: We successfully established an AI-empowered AIO workflow for initial radiotherapy of NPC, confirming its feasibility and safety for clinical application.
Infiltrating B-cell subtypes and associated hub genes in nasopharyngeal carcinoma identified from integrated single-cell and bulk-RNA sequencing data.
Authors: Zhong Fangyan , Lu Tianzhu , Chen Junjun , Zhang Lin , Liu Zhiliang , Guan Chunhong , Xiong Xiaopeng , Gong Xiaochang , Li Jingao
Published: August 2024

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Background: Nasopharyngeal carcinoma (NPC) is associated with lymphocyte infiltration; however, the majority of research on NPC has focused on the role of T cells, with relatively little known about the roles of B cells and their subtypes. Therefore, we evaluated the prognostic value of CD20+ B cell density and B-cell subtypes along with their functional enrichment and hub genes in NPC. Methods: The prognostic value of CD20+ B-cell density for distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS) was explored by immunohistochemistry using multivariate analysis. Transcriptomic expression data from Gene Expression Omnibus (GEO) datasets were analyzed to identify B-cell subtypes and their functional enrichment in NPC tissues. Pseudotime trajectory analysis was performed to evaluate the B-cell differentiation trajectory and hub genes were identified using Cytoscape software. Results: Patients with NPC exhibiting a high infiltrating density of CD20+ B cells showed significantly better 5-year DMFS, OS, and PFS compared to those of patients with a low infiltrating density. Naïve B cells, switched memory B cells, exhausted B cells, and plasma cells were identified as key B-cell subtypes infiltrating NPC tumors, with naïve B cells showing the highest infiltration levels associated with a better prognosis. Naïve B cells were closely associated with immune pathways and the hub genes were typical markers for T and B cells. Conclusions: A high infiltrating density of B cells showed strong prognostic value in patients with NPC. Naïve B cells may play an important role in tumor immunity for NPC.
Resolving disparities in access to cancer care in LMIC-positive learning using a 10-year-old model.
Authors: Pendharkar Dinesh , Tripathi Chandramauli , Nagar Ashok Kumar
Published: August 2024

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Background: Despite significant advances in cancer diagnosis and treatment, there are wide disparities in access to cancer care, more so in low- and middle-income countries. The problem is multifactorial, such as patient-related, health system-related, socio-cultural-related to language and literacy, and socio-cultural-related to beliefs and stigma. These disparities extend across the cancer continuum, from diagnosis to end-of-life care. It is imperative to address these disparities. Here we report 10-year experience from an innovative access delivery model in one go, comprehensively addressing many of these challenges. Methods: Learning from the WHO framework of health system strengthening, a model that affects the major contributors to health system strengthening was developed. These include government-owned health departments, district hospitals, and physicians. Various regulations strengthened each of these components. The regulations were issued to create systems in district hospitals, train an alternative oncology workforce, and make oncology drugs available in the periphery. This measure allowed cancer-care-related services to be feasible in the existing peripheral health system. Results: In 2014, one of the states in India decided to initiate cancer care services in government-run district hospitals. One physician and two nurses from every district hospital were trained to offer cancer-related services locally from diagnosis to end-of-life, including cancer chemotherapy, under the 24 x7 mentorship of a senior oncologist. To date, more than 250 physicians and 500 nurses have been trained in this field. The program has been extended to eight states and 198 districts, covering an area of over a million square kilometers and a population of over 380 million. Data from only one district alone showed that nearly 7000 new patients availed of services (average 700 per year) with more than 17000 sessions of chemotherapy (Table). Conclusions: The majority of the world, including LMICs, is dependent on the services provided by government-run health institutions. The empowerment of government health systems appears to be the single most important factor in improving access to cancer care. This model of cancer cere delivery has consistently proven its robustness, replicability, and scalability. This finding deserves consideration for further research and expansion to other countries. [Table: see text]
Preliminary analysis of PD-1 inhibitors combined with chemotherapy as neoadjuvant therapy for local advanced non-small cell lung cancer (NSCLC).
Authors: Li Hongru , Yang Xiao jie , Guo Tianxing , Fang Jiabin , Xu Nengluan , Chen Sufang , Zhang Qiongyao , Lin Ying , Pan Xiaojie
Published: August 2024

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Background: The benefits of neoadjuvant immunotherapy and chemotherapy for resectable NSCLC suggest that this combined treatment may provide more surgical opportunities and survival benefits for potentially resectable locally advanced NSCLC. Methods: We retrospectively collected data from 28 patients with stage III EGFR/ALK/ROS wild-type NSCLC. Eligible patients received 2-8 cycles of neoadjuvant chemoimmunotherapy (squamous carcinoma: PD-1 inhibitor combined with albumin-bound paclitaxel and cisplatin/carboplatin; adenocarcinoma: PD-1 inhibitor combined with pemetrexed and carboplatin), followed by re-evaluation for surgery. Afterwards, patients underwent surgery after downstaging, with some receiving adjuvant immunotherapy maintenance for one year. Primary endpoints included major pathological response (MPR), pathological complete response (pCR), progression-free survival (PFS), and overall survival (OS). Results: All 28 patients were male, with 7 (25%) in stage IIIA, 10 (35.7%) in IIIB, 4 (14.3%) in IIIC, 2 (7.14%) in IVA, and 2 (7.14%) in IVB. There were 22 cases of squamous cell carcinoma, 4 of adenocarcinoma, 1 of large cell lung cancer, and 1 of lymphoepithelioma-like carcinoma. 23 patients (82.1%) completed neoadjuvant treatment and underwent resection, achieving 100% R0 resection rate (23/23); 5 patients did not undergo surgery, 3 of whom received combined radiochemotherapy due to disease progression, 1 delayed surgery due to immunotherapy associated myocardial damage, and 1 died from massive hemoptysis and hemorrhagic shock. The objective response rate (ORR) was 60.7%, 95%CI [40.6-78.5%] and the disease control rate (DCR) was 85.7%, 95%CI [67.3-96.0%]. Among the 23 patients who underwent surgery, the pCR was 60.9%, 95%CI [38.5-80.3%], MPR was 4.3%, 95%CI [0.1-21.9%], clinical downstaging rate was 50%, 95%CI [30.6-69.4%] and pathological downstaging rate was 86.9%, 95%CI [66.4-97.2%]. 17 patients (77.3%) underwent lobectomy, and 5 (22.7%) underwent bilobectomy with a median blood loss of 100 ml, IQR [55.0-100]. There were no surgery-related deaths. Postoperatively, one patient developed chylothorax, one had a lung infection, and the two improved after conservative treatment. 11 patients (47.8%) received post-surgery immunotherapy maintenance, and 2 of them (8.7%) developed immune-related pneumonia. As of April 7, 2024, the median follow-up time was 21.5 months (95%CI: 17-34 Mo), At 12 months。 PFS rate was 82.1% (95%CI: 69.1-97.6%); OS rate was 96.3% (95%CI: 89.4-100%). Conclusions: Neoadjuvant immunotherapy combined with surgery for unresectable locally advanced NSCLC may benefit patients and significantly extend survival.
Effect of ac4C acetyltransferase NAT10 on tumor progression via ATF4/ASNS mediated asparagine biosynthesis in osteosarcoma.
Authors: Zou Yutong , Xie Xianbiao
Published: August 2024

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Background: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, characterized by high malignancy, high mortality, and high disability rates. Investigating the mechanism of osteosarcoma progression, identifying new targets, and developing effective therapy are of great significance for improving patient clinical outcomes. NAT10-mediated ac4C modification is widely present in mRNA and plays important roles in multiple biological processes of mRNA. NAT10 and ac4C modification also play a crucial role in the occurrence and development of malignant tumors such as bladder cancer, esophageal cancer, and breast cancer. Methods: Through RNA-seq and functional screening, NAT10 was identified as the potential therapeutic target. The biological functions of NAT10 and ac4C modification in osteosarcoma were explored in vivo and in vitro. Downstream target of NAT10 was identified through acRIP-seq combined with RNA-seq. The ac4C modification of downstream target gene were detected using RIP-qPCR and its regulatory effect on mRNA stability was explored using RNA half-life analysis. Drug screening was performed using FDA-approved drugs and a small molecule compound library to identify NAT10 inhibitors. The efficacy of inhibitors in osteosarcoma treatment is validated through in vivo, in vitro experiments and patient-derived tumor xenograft (PDX) models. Results: Functional screening targeting RNA modification regulatory factors demonstrated that inhibiting NAT10 significantly reduced the proliferation, migration and invasion of osteosarcoma cells. NAT10 knockout significantly inhibited the proliferation and metastasis of osteosarcoma cells, as well as the malignant progression in vivo. The acRIP-seq and RNA-seq revealed that ATF4 is a downstream target gene regulated by NAT10 in osteosarcoma. NAT10 promoted ac4C modification of ATF4 mRNA, enhanced the stability of ATF4 mRNA, and ATF4 promoted the transcription and expression of ASNS. ASNS catalyzes the synthesis of asparagine (Asn), thereby promoting the malignant progression of osteosarcoma. Drug screening identified Paliperidone and AG-401 as potential inhibitors of NAT10. Through cell functional experiments, orthotopic osteosarcoma models, organoids model, and PDX models, it was demonstrated that Paliperidone and AG-401 can inhibit the malignant progression of osteosarcoma. Conclusions: NAT10 was highly expressed in osteosarcoma and associated with patient prognosis. Through ac4C modification, NAT10 regulated the synthesis of asparagine mediated by ATF4/ASNS, providing materials for protein and nucleotide synthesis in tumor cells, thus promoting the malignant progression of osteosarcoma. Paliperidone and AG-401 were identified as potential NAT10 inhibitors and targeting NAT10 could be a promosing strategy in osteosarcoma treatment.