bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the Anticancer Mechanisms of Prodigiosin by inhibiting of CDK1, TOP2A, and AURKB Expression in Cervical Carcinoma
Authors: Zhu Zhenkun , Jiang Chunfan , Xiang Chunxiang , Chen Qianbao , Yang Mei , Tang Mengjun , Xing Hui
Published: January 2024

Prodigiosin (PG) demonstrates a selective targeting effect on tumor cells. However, its role in cervical carcinoma is still being studied. In this study, we aim to study the specific targets and mechanism of PG in cervical carcinoma. We employed GO enrichment and KEGG analysis to identify core genes in CC patients. To corroborate the expression levels of these core genes, we used staining and RT-PCR on both normal and tumor tissues. Following this, the specific effects of PG on Hela, H8, and A549 cells were compared. After PG treatment, cell viability was evaluated using a CCK8 assay at various PG concentrations. Apoptosis in Hela cells was determined through flow cytometry post-PG treatment, and the expression of target genes was measured via RT-PCR. Our analysis highlighted CDK1, TOP2A, and AURKB emerging as core genes. The expression of CDK1, TOP2A, and AURKB, both at the protein and gene levels, was found to be higher in cervical carcinoma tissues compared to controls. Furthermore, lower PG concentrations diminished the viability of Hela and A549 cells without significantly impacting H8 cells. PG was observed to induce apoptosis in Hela cells by reducing the expression of CDK1, TOP2A, and AURKB genes.
Use of dental care services among adolescents living with HIV on Antiretroviral Treatment in Kampala, Uganda: a cross-sectional study
Authors: Nakyonyi Maria Gorretti , Birungi Nancy , Mwesigwa Catherine Lutalo , Åstrøm Anne Nordrehaug
Published: January 2024

Objective
The main purpose of this study to assess the prevalence and socio-behavioural determinants of ever-use of dental care services among the adolescents aged 10–18 years, living with HIV on Antiretroviral treatment (ART), attending selected HIV clinics in Kampala, Uganda.
Methods
A cross-sectional study was carried out between March and September 2020. The study conveniently recruited 154 adolescents between 10–18 years from 4 specific HIV clinics in Kampala. The Andersen’s behavioral model guided the selection of variables in terms of ever use of dental care services as the outcome- and predisposing, enabling, need related factors and dental health related behavior as exposure variables. Data was analyzed using Fischer’s exact test for cross-tabulation and modified Poisson regression for multivariate analysis.
Results
The prevalence of ever-use of dental care services was 12.3%. The adolescents aged 14–18 years were more likely to have used dental care services (Prevalence ratio (PR) of 3.35 (Confidence Interval (CI) 1.48–7.59) than those aged 10–13 years. Fear of spread of HIV was negatively associated with ever-use of dental care services (PR of 0.06 and CI of (0.01–0.44). Participants who were afraid of going to the dentist were more likely to have ever used dental care services (PR of 2.98 and CI of 1.41–6.30) than those not afraid. Failure to receive dental treatment because it was not part of the medical appointment had a positive association with ever-use of dental care services (PR of 4.50 (CI: 1.14–17.80). Those who were satisfied with their dental condition were less likely to have ever-used dental care services (PR of 0.21 and CI of (0.05–0.94). Bad oral odor was positively associated with ever-use of dental care services with a PR of 2.80 and CI of 1.19–6.60. Use of soap for toothbrushing was positively associated with ever-use of dental care services (PR of 2.51, CI of 1.47–4.28).
Conclusion
The study found low frequency of dental care use among HIV infected adolescents in Kampala, Uganda, with age being a predisposing factor. Enabling factors included fear of HIV spread, dental appointment failure, and satisfaction with dental condition and bad oral odor while under personal oral hygiene and dental practices, use of soap for toothbrushing was an important association of use of dental care.
Advancing unmanned surface vehicle heading control: real-sea validation of a practical model predictive controller for a medium-scale hybrid-power trimaran
Authors: Wang Jian , Wang Jun , Liang Xiaofeng , Liu Junjie , Cheng Shunzhao , Yi Hong
Published: January 2024

The development of medium- to large-scale, high-performance, and environmentally-friendly unmanned surface vehicles (USVs) is a burgeoning trend in intelligent marine systems. The heading controller is crucial for USVs to execute various missions, especially given their inherent underactuation characteristics. Despite extensive exploration of numerous control strategies, the majority of studies have been confined to smaller, conventional USVs with an emphasis on simulation validation. This limitation stems from the significant gap between theory and practical engineering. We here introduce a model predictive controller for the heading control of a medium-scale hybrid-power unmanned trimaran and validate its performance in real sea. This controller directly accounts for the amplitude and increment constraints of the water-jet thrust angle, and its asymptotic stability is established with a terminal cost. Experimental results demonstrate that the controller’s ability to effectively track and maintain constant desired heading angles without any disturbance compensation, surpassing the traditional proportional-integral-derivative controller in terms of response speed, overshoot, steady-state error, and robustness. We further showcase the successful application of this controller in path-following missions, evidencing its precise adherence to desired paths. A critical aspect of our research is monitoring the controller’s execution time in all experiments, affirming its real-time response capabilities given the onboard hardware’s limited computational power. This research not only contributes a significant advancement in the field of USV control but also provide a new solution for the integration of theoretical control strategies into practical marine engineering.
Sexual Health Literacy Confidence Among Urology Resident Physicians
Authors: Horwitz Rainey , Lewis Kevin , Khooblall Prajit , Haile Eiftu , Lundy Scott , bajic Petar
Published: January 2024

Introduction: Despite the importance of sexual health, physicians may not be adequately trained and equipped to diagnose and treat sexual dysfunction. It is crucial that urologists are trained to ask detailed questions about sexual health, counsel on healthy sexual habits, and appropriately identify and treat sexual dysfunction.
Objective: To determine the level of comfort among urology residents in taking a comprehensive sexual health history, identifying sexual dysfunction, and treating patients of various gender identities and sexual orientations.
Methods: An anonymous electronic survey was distributed to current urology residents in the United States. The survey contained five demographic questions and twenty-three questions tied to previously established sexual health competency domains.
Results: A total of 52 urology residents participated with post-graduate years ranging from one to six. 46.3% reported having any formal sex education during residency. 27% felt comfortable answering questions about anal stimulation devices and 35% felt comfortable answering questions about vaginoclitoral stimulation devices. Greater than 94% of residents felt “very comfortable” or “somewhat comfortable” with describing cisgender male sexual dysfunction and performing a physical exam for a cisgender male with sexual dysfunction, but 59% felt the same towards cisgender female sexual dysfunction. When counseling transgender men or women on sexual practices, therapies, or surgeries, 29% felt comfortable.
Conclusion: There are knowledge gaps in sexual health literacy confidence among urology residents surveyed. Women and sexual and gender minority patients may be at higher risk. Sexual health education optimization during urology residency has the potential to promote improved understanding of sexual health and evaluation and management of sexual dysfunction in general.
T Cell-Mediated Tumor Killing Sensitivity Gene Signature-Based Prognostic Score For Acute Myeloid Leukemia
Authors: Pan Yiyun , Xie FangFang , Zeng Wen , Chen Hailong , Chen Zhengcong , Xu Dechang , Chen Yijian
Published: January 2024

Background and Objective: Acute myeloid leukemia (AML) is an aggressive, heterogenous hematopoetic malignancies with poor long-term prognosis. T-cell mediated tumor killing plays a key role in tumor immunity. Here, we explored the prognostic performance and functional significance of a T-cell mediated tumor killing sensitivity gene (GSTTK)-based prognostic score (TTKPI).
Methods:Publicly available transcriptomic data for AML were obtained from TCGA and NCBI-GEO. GSTTK were identified from the TISIDB database. Signature GSTTK for AML were identified by differential expression analysis, COX proportional hazards and LASSO regression analysis and a comprehensive TTKPI score was constructed. Prognostic performance of the TTKPI was examined using Kaplan-Meier survival analysis, Receiver operating curves, and nomogram analysis. Association of TTKPI with clinical phenotypes, tumor immune cell infiltration patterns, checkpoint expression patterns were analysed. Drug docking was used to identify important candidate drugs based on the TTKPI-component genes.
Results: From 401 differentially expressed GSTTK in AML, 24 genes were identified as signature genes and used to construct the TTKPI score. High-TTKPI risk score predicted worse survival and good prognostic accuracy with AUC values ranging from 75%-96%. Higher TTKPI scores were associated with older age and cancer stage, which showed improved prognostic performance when combined with TTKPI. High TTKPI was associated with lower naïve CD4 T cell and follicular helper T cell infiltrates and higher M2 macrophages/monocyte infiltration. Distinct patterns of immune checkpoint expression corresponded with TTKPI score groups. Three agents; DB11791 (Capmatinib), DB12886 (GSK-1521498) and DB14773 (Lifirafenib) were identified as candidates for AML.
Conclusion: A T-cell mediated killing sensitivity gene-based prognostic score TTKPI showed good accuracy in predicting survival in AML. TTKPI corresponded to functional and immunological features of the tumor microenvironment including checkpoint expression patterns and should be investigated for precision medicine approaches.
Fractal analysis of mechanical properties in folded graphene aerogels
Authors: Liu Jingguo , Li Haiming , Li Hongyan , zhang Hai , Zhang Baolian , Wei Dongqing , Liao Xiaolan , Ding Wei
Published: January 2024

Origami structures contributed to the design of composite materials with excellent mechanical properties. In our previous work, the GO sheet was folded through the coordination and electrostatic interaction among oxygen atoms and Cu2+. The folded graphene aerogel (fGA) was constructed with folded graphene oxide sheets (fGO). However, the effect of pore structure parameters on the mechanical properties of fGA was neglected. Therefore, based on fractal theory, the pore structure of fGA was parametrically quantified using the fractal dimension (Df) in this paper. The elastic behavior of fGA was investigated through the mean-field homogenization fractal model (MHFM). The results showed that the fGA elasticity property exhibited a non-linear decreasing trend as the Df increased. The fGA with abundant pore structures was constructed by fGO, and these pores were essential for the structural stabilization of the aerogels. The excellent mechanical properties were possessed in fGA. As the pore size distribution of fGA became uniform, the variation of its elastic properties tended to stabilize.
Cholangiocarcinoma identified in perforated choledochal cyst in a 3-year-old boy
Authors: Yu Lun , Xiu Wenli , Yue Aimei , Hao Xiwei , Jiang Zhong , Wu Jie , Dong Qian
Published: January 2024

Cholangiocarcinoma in patients with Choledochal cyst is rare in childhood, however seriously affect the prognosis of the disease. The key to addressing this situation lies in the complete excision of extra-hepatic cyst. We present a case report of a 3-year-old boy who was found to have a cyst wall perforation during the surgical procedure, and postoperative pathology revealed cholangiocarcinoma confined to the mucosa layer. Preoperative 3D simulation based on CT data plays an important role in the treatment of this patient.
Radiation-Induced Xerostomia in Patients with Head and Neck Cancer Treated with Comprehensive Salivary Gland-Sparing Helical Tomotherapy Technique: Based on a Backpropagation Artificial Neural Network
Authors: Teng Feng , Wang Shijie , Li Kaixuan , Meng Lingling , Ju Zhongjian , Dai Xiangkun , Zhang Xinxin , Ma Lin , Zhu Guangying
Published: January 2024

Background The aim of this study was to create a backpropagation artificial neural network (BPANN) model for gauging the risk of developing xerostomia (dry mouth) due to targeted radiotherapy in patients with head and neck cancer (HNC) who underwent comprehensive salivary gland-sparing helical tomotherapy (HT).Methods A total of 246 HNC patients treated with salivary gland-sparing HT were included in this study prospectively from February 2016 to August 2018. The baseline characteristics and clinical data of 222 patients were collected and analyzed. The potential variables included age, sex, tumor type, radiation dose to the salivary glands, and xerostomia questionnaire score. These variables were adjusted using multivariate linear regression. The BPANN model was constructed to predict the likelihood and severity of xerostomia at both 1 and 2 years after radiotherapy. Model evaluation was based on the confusion matrix table and the area under the receiver operating characteristic curve (AUC of the ROC).Results The BPANN model revealed that the risk of radiation-induced xerostomia could be evaluated by evaluating the age, sex, tumor type, and radiation dose applied to specific salivary glands (parotid glands, submandibular glands, oral cavity, and tongue glands). Multivariate analysis indicated that age, sex, and submandibular gland dose were the primary influencing factors for xerostomia. Both prediction models demonstrated strong performance, as reflected in the confusion matrix table and the AUC of ROC curve.Conclusions The BPANN represents a potential and recommended predictive tool for assessing the likelihood of xerostomia induced by salivary gland-sparing helical tomotherapy.Trial registration: This study was registered with the Chinese Clinical Trial Registry (ChiCTR-ONN − 17010597).
Antibiotic resistance of Escherichia coli in Jordan
Authors: Shalabi Marwan , Al-Tamimi Mohammad , Albalwi Abdallah , Balawi Dua'a , Altarawneh Shahed , El-sallaq Mariam , Albalawi Hadeel , AbuRaideh Jumana , Khasawneh Ashraf
Published: January 2024

Background: Escherichia coli (E. coli) is among the most common causes of infections worldwide. Antibiotic resistance accounts for over 50% of E. coli infections, which is mediated by extended spectrum β-lactamases (ESBLs), AmpC β-lactamases, carbapenemase, and other mechanisms. Data on AmpC, carbapenemase, aminoglycosides and quinolones resistance of E. coli in Jordan are very limited. Aim: The aim of this study is to determine the molecular and phenotypic prevalence of antibiotic-resistant E. coli in Jordan.
Methods: 153 E. coli isolates collected from multiple Jordanian hospitals were tested for species identification, antibiotics susceptibility, and resistance genes.
Results: 153 E. coli isolates were collected from PHH (23%) and Islamic hospital (77%) including 75.8% females with a mean age of 47.09 ± 25.32. Most samples were collected from the emergency department (29.7%) and urine samples were the major source (82.9%). For AmpC detection, 67 (57.8%) samples were resistant to cefoxitin, 13 (23.2%) were positive for AmpC disk test, all tested samples were negative for CMY-1 gene, while 15 (14.4%) samples were positive for CMY-2 gene. Regarding aminoglycoside resistance, 54 (38%) strains were resistant to gentamycin, 3 (2.1%) were resistant to amikacin, and 94 (61.4%) samples had aac6’-Ib-cr gene. For fluoroquinolones resistance, 92 (65.7%) isolates were resistant to ciprofloxacin, 65 (47.1%) were resistant to levofloxacin, and 102 (98%) isolates were positive for gyrA gene. Finally, 3 (2%) isolates were resistant to imipenem and meropenem, however carbapenemase genes including: KPC, OXA-48, IMP, and VIM genes were negative in all samples.
Conclusion: Understanding the molecular and phenotypic characteristics of antibiotic-resistant E. coli will help to guide proper antibiotic therapy and combat microbial resistance in Jordan.
Social issues among the medical professionals during COVID-19 pandemic: An Indian Scenario
Authors: Nair Padmakumar Krishnankutty , Dsoza Russel F , Duarte Ivone , Nunes Rui
Published: January 2024

Background
Corona virus pandemic was a global pandemic due to Corona virus which resulted social and economic disruption around the world and medical professionals were not an exception.
Methodology & study population
Descriptive Cross-sectional questionnaire-based survey was conducted among the medical professionals in India to find out the social issues faced during COVID pandemic.
Results
Medical professionals faced isolation, harassment denial of accommodation (38.89%) and untoward incidents (26.68%). Pandemic affected the income for majority and they also faced expenditure in the form of investment in health insurance schemes. Bio medical waste management was fairly good and medical professionals were aware of the biomedical waste management guidelines. Majority (87.63%) were aware of the guidelines regarding Pandemic related biomedical waste management and 67.74% were trained in biomedical waste management rules which exist in the country.
Conclusion
Pandemic raised social issues among medical professionals in the form of stigma, violence, decline in revenue, increased insurance expenditure. Guidelines and training were obtained for majority of medical professionals regarding biomedical waste management.
Does chronic endometritis affect pregnancy outcomes in patients with endometriosis associated infertility? A retrospective cohort study
Authors: Lin Shunhe , Xie Xi , Chen Yishan , Huang Penghui , Zhang Jinna , Liu Chaobin , Lin Guan , wang Yi , Guo Yuyan
Published: January 2024

Background: Endometriosis (EMS) and chronic endometritis (CE) often coexist. Laparoscopic and hysteroscopic surgery surgery is one of the main methods for diagnosing and treating these conditions. The objectives of this study were to examine the clinical characteristics and prognosis of surgically diagnosed EMS complicated by CE and to assess the reproductive outcomes during subsequent pregnancies.
Methods:A total of 1574 infertile patients were included in this study between January 2018 and December 2020. 685 patients were diagnosed with endometriosis who were further divided into two groups: a CE group consisting of 318 patients and a non-CE group consisting of 367 patients. Within the cohort who suffered from CE, a subset of postoperative care clinical pregnant women (n=123) was selected to form the study group. The control group consisted of women undergoing singleton pregnancy (n=369) who underwent delivery during the same period. Data on clinical statuses and complications during pregnancy and delivery were collected from hospitals and through telephone interviews.
Results: The CE prevalence rate in women with EMS was 46.42%. Among the 318 women who were diagnosed with posterior CE, 135 achieved pregnancy. The cumulative clinical pregnancy rate was found to be significantly higher in groups with endometriosis fertility index (EFI) scores ranging from 7 to 8 and from 9 to 10 compared to groups with EFI scores below 7. Furthermore, women with both EMS and CE had a higher risk of experiencing complications during pregnancy, including placenta previa (13.01%), gestational hypertension (5.69%), and cesarean section delivery (59.34%).
Conclusions:Patients diagnosed with endometriosis exhibited a heightened prevalence of chronic endometritis. Our investigation revealed that combined hysteroscopic and laparoscopic surgery proved to be a successful approach in augmenting the overall pregnancy rate. Furthermore, women afflicted by both EMS and CE face an independently escalated susceptibility to placenta previa, gestational hypertension, and cesarean delivery.
Multimorbidity, Health Literacy, and Quality of Life Among Older Adults in an Urban Slum in India: A Community-Based Cross-Sectional Study
Authors: M Yogesh , Makwana Naresh , Damor Naresh , Trivedi Nidhi
Published: January 2024

Background: India is experiencing a rising burden of multimorbidity due to an aging population and epidemiological transition. Older adults residing in urban slums are especially vulnerable due to challenges in managing multiple comorbidities amid deprived living conditions. This study aimed to assess the prevalence of multimorbidity, associated health literacy, and quality of life impact in this marginalized population.
Methods and Materials: A community-based cross-sectional study was conducted among 800 adults aged ≥65 years in an urban slum in Gujarat, India. Participants were selected through multistage random sampling. Data on sociodemographics, chronic conditions, health literacy (HLS-SF-47 scale), quality of life (SF-12 scale), physical activity, social support, smoking, alcohol use, diet, and healthcare access were collected. and were collected. Multimorbidity was defined as the presence of ≥2 conditions. Categorical variables are presented as the frequency and percentage, and numerical variables are presented as the mean ± SD. Logistic regression analyses were applied to test the relationship between categorized independent and dependent variables, and all tests were two-tailed, with statistical significance set at the probability value (P <0.05).
Results: The prevalence of multimorbidity was 62.5% (500/800). Multimorbidity was significantly associated with lower physical component summary (PCS) and mental component summary (MCS) scores on the SF-12 (p<0.001). Nearly half (48%) of the older adults with multimorbidity had inadequate health literacy, compared to 20% of those without multimorbidity. After adjustment, inadequate health literacy increased the likelihood of having multimorbidity by more than 4 times (AOR 4.2, 95% CI 2.1-8.5). Older age (AOR 1.05, 95% CI 1.02-1.09; p=0.002), female sex (AOR 1.86, 95% CI 1.12-3.08; p=0.016), widowhood (AOR 2.05, 95% CI 1.15-3.65; p=0.015), no formal education (AOR 3.12, 95% CI 1.52-6.41; p=0.002), low socioeconomic status (AOR 2.35, 95% CI 1.22-4.52; p=0.011), being physically inactive (AOR 1.68, 95% CI 1.02-2.77), and lacking social support (AOR 1.57, 95% CI 1.01-2.45) were associated with greater odds of multimorbidity.
Conclusion: There is a high burden of multimorbidity among urban slum dwellers aged ≥65 years in India, which is strongly linked to inadequate health literacy, physical inactivity, and poor social support. Improving health literacy and addressing modifiable social determinants of health are essential to reducing multimorbidity prevalence in this marginalized population.
Enhancing Atrial Fibrillation Prediction Using Multimodal Neural Networks and XGBoost Integration
Authors: Rawshani Araz , Rawshani Aidin , Smith J. Gustav , Borén Jan , Bhatt Deepak L. , Börjesson Mats , Engdahl Johan , Lundgren Peter , Louca Antros , Råmunddal Truls , Andersson Erik , Omerovic Elmir , Mandalenakis Zacharias , Gupta Vibha
Published: January 2024

Atrial fibrillation (AF), a prevalent cardiac arrhythmia, poses significant health risks, emphasizing the critical need for accurate and timely detection to develop robust methodologies and ensure effective intervention. This study propels the field of AF detection through detailed electrocardiogram (ECG) analysis, employing sophisticated deep learning models and multimodal frameworks aimed at leveraging the complementary strengths of both deep learning and additional data sources, including heart rate variability (HRV) features and demographic data. The potential enhancement from the integration of high-level features from a deep neural network with XGBoost is also assessed. Our evaluation involves 35,634 recordings from three diverse public 12-lead ECG databases (CPSC-Extra, PTB-XL, and Georgia) with physician-interpreted AF labels, revealing notable performance disparities among various CNN architectures. AlexNet and VGG-16, less complex models, exhibited high performance both individually and in multimodal settings. Specifically, AlexNet achieved 96.80% AUC-ROC individually and 97.23% in multimodal modeling, while VGG-16 reached 97.13% in multimodal approach. The inclusion of HRV parameters positively impacted performance, while demographic data showed limited influence. Integrating high-level features with XGBoost increases overall accuracy but reduces AUC-ROC; for AlexNet, an AUC-ROC of 90.92% was observed. This study offers valuable insights into optimal model configurations, emphasizing the pivotal impact of a multimodal framework.
Basic research on multilayer composites based on fly ash and natural fibers
Authors: Bąk Agnieszka , Mikuła Janusz , Łach Michał
Published: January 2024

New restrictions on carbon dioxide emissions and electricity consumption are currently being introduced around the world. In many countries, innovative solutions are being used to reduce CO2 emissions and reduce material and energy consumption. The present work is related to the study of innovative binders based on geopolymers reinforced with composite bars and containing natural fibers for the production of layered building envelopes. The paper will present preliminary results of research on composites based on fly ash and natural materials of plant origin. The natural materials used to produce the samples are completely biodegradable. A 10-mol solution of sodium hydroxide with an aqueous solution of sodium silicate was used for the alkaline activation of geopolymers. The publication presents the results of physicochemical tests of base materials and natural materials, studies of thermal properties of fibers, mats, felts, and wools, morphology of fiber structure and texture, as well as physical and thermal properties of finished multilayer partitions. The results indicate the great potential of these materials in prefabrication and structural insulation applications. The work may have future applications in energy-efficient and low-carbon construction.
Influence of SLC40A1 on Cytokine Interaction and Immune Infiltration in Glioblastoma
Authors: Jiang Jiahao , Duan Riquan , Zhu Junle , Yan Junqing , Ye Jingliang , Luo Chun
Published: January 2024

Numerous studies have explored the various functions of SLC40A1 in cancer development. However, the role of SLC40A1 in primary glioblastoma necessitates further investigation. Initially, we observed that GBM patients with high SLC40A1 expression had a more favorable prognosis compared to those with low expression levels, as evidenced by the analysis of the TIMER database. Subsequent analysis using the TCGA database enabled us to identify potential mechanisms. Further analyses, including GO, KEGG, GSEA, immune infiltration, and correlation analyses, revealed that SLC40A1 primarily affected cytokine interactions, particularly with CCL14 and IL18, resulting in changes in the immune microenvironment and ultimately leading to better prognosis in GBM patients. We validated our findings by examining a tissue microarray with 180 samples, confirming that GBM patients with high SLC40A1 protein expression exhibited more favorable prognostic outcomes compared to those with low expression levels. Immunofluorescence analysis also showed a significant correlation between SLC40A1 protein expression and the expression of IL18 and CCL14 proteins. These findings suggest that SLC40A1 may play a role in GBM pathogenesis by modulating the tumor immune microenvironment through the regulation of IL18 and CCL14. Hence, targeting SLC40A1 might offer potential benefits for immunotherapeutic interventions and prognostic assessments in GBM patients.
Burden re-analysis of neurodevelopmental disorder cohorts for prioritization of candidate genes and establishment of LEO1 as a novel disease gene
Authors: Weckhuysen Sarah , smal Noor , Majdoub Fatma , Janssens Katrien , Reyniers Edwin , Meuwissen Marije , Ceulemans Berten , Northrup Hope , Hill Jeremy , Liu Lingying , Errichiello Edoardo , Gana Simone , Strong Alanna , Rohena Luis , Franciskovich Rachel , Murali Chaya , Huybrechs An , Sulem Telma , Fridriksdottir Run , Sulem Patrick , Stefansson Kari , Bai Yan , Rosenfeld Jill , Lalani Seema , Streff Haley , Kooy Frank
Published: January 2024

This study aimed to uncover novel genes associated with neurodevelopmental disorders (NDD) by leveraging recent large-scale de novo burden analysis studies to enhance a virtual gene panel used in a diagnostic setting. We re-analyzed historical trio-exome sequencing data from 745 individuals with NDD according to the most recent diagnostic standards, resulting in a cohort of 567 unsolved individuals. Next, we designed a virtual gene panel containing candidate genes from three large de novo burden analysis studies in NDD and prioritized candidate genes by stringent filtering for ultra-rare de novo variants with high pathogenicity scores. Our analysis revealed an increased burden of de novo variants in our selected candidate genes within the unsolved NDD cohort and identified qualifying de novo variants in seven candidate genes: RIF1, CAMK2D, RAB11FIP4, AGO3, PCBP2, LEO1, and VCP. Clinical data were collected from six new individuals with de novo or inherited LEO1 variants and three new individuals with de novo PCBP2 variants. Our findings confirm LEO1 as a risk gene for autism and intellectual disability. Furthermore, we prioritize PCBP2 as a candidate gene for NDD associated with motor and language delay. In summary, by leveraging de novo burden analysis studies, employing a stringent variant filtering pipeline, and engaging in targeted patient recruitment, our study contributes to the identification of novel genes implicated in NDDs.
Clinical implementation and evaluation of deep learning-assisted automatic radiotherapy treatment planning for lung cancer
Authors: Wang Ningyu , Fan Jiawei , Xu Yingjie , Yan Lingling , Chen Deqi , Wang Wenqing , Men Kuo , Dai Jianrong , Liu Zhiqiang
Published: January 2024

Background and purpose The purpose of this study is to investigate the clinical application and assessment of deep learning (DL)-assisted automatic radiotherapy planning for lung cancer patients.Materials and methods We developed a deep learning model for predicting patient-specific dose that was trained and validated on a dataset of 235 lung cancer patients, and the model was integrated into clinical workflow to assist planners in generating treatment plans. We retrospectively selected and recovered additional 50 clinically treated lung cancer patients’ manual volumetric modulated arc therapy (VMAT) plans with different target volumes and different treatment patterns. Subsequently, automatic plans were generated for each of these patients. Both automatic and manual plans were subsequently compared in terms of overall plan quality metric (PQM), target coverage and homogeneity, organ at risk (OAR) sparing, monitor units (MUs), and planning time. Additionally, qualitative reviews of automatic and manual plans were implemented by four expert reviewers to assess the clinical applicability of DL-assisted automatic plans.Results The average PQM score was 40.7 ± 13.1 for manual plans and 40.8 ± 13.5 for automatic plans, and they had equivalent overall plan quality. The targets coverage and homogeneity of the automatic plans were considered equivalent or superior when compared to manual plans. Both plans had their own advantages in OAR sparing, such as better sparing of lung for manual plans and better sparing of heart for automatic plans. It is worth to note that the average planning time of automatic plans was reduced from 103.1 ± 18.5 minutes to 32.6 ± 5.3 minutes (P<0.001) and the MUs were reduced from 789.9 ± 234.3 to 692.5 ± 210.7 (P<0.001). In qualitative evaluation, automatic plans were deemed to be clinically acceptable for treatment in 88% of reviews (176/200), and all were accepted after fine tuning. Most expert reviews indicated a preference for equivalence between automatic and manual plans when making their selection.Conclusion The DL-assisted lung cancer plans demonstrated comparable or superior quality to manual plans, improved planning and treatment efficiency, and significantly reduced planning time and MUs. It has the potential to enhance the workflow of radiotherapy departments, ultimately providing tangible benefit to lung cancer patients.
Risk Assessment of Equipment Research Project Costs Based on FAHP-CRITIC Combined Weights for 2D Cloud Models
Authors: Zhu Chen , Sun Shengxiang , Chen Tong , Zhong Qianghui , Liu Haobang , Li Jing , He Dubo
Published: January 2024

The development process of equipment research projects is fraught with uncertainties, making it challenging to provide an accurate and objective evaluation of their development costs. To enhance the accuracy of cost prediction for equipment research projects, it is essential to consider the cost risk level and conduct relevant research on cost risk assessment. This study proposes an improved two-dimensional cloud model that integrates qualitative concepts and quantitative data for researching equipment projects. An assessment index system is constructed with three primary indicators and twelve secondary indicators. The main factors affecting the cost are comprehensively considered. The probability of overspending and the degree of impact of overspending are taken as the basic variables for assessing each indicator according to the definition of cost risk. The study combined the Fuzzy Analytic Hierarchy Process (FAHP) method with the Criteria Importance Though Intercrieria Correlation (CRITIC) method using the cooperative game method to determine the weights of each assessment indicator. Subsequently, a two-dimensional cloud model was established to obtain the cloud eigenvalues. A two-dimensional cloud diagram was drawn through MATLAB to initially determine the risk level, and the closeness was calculated to accurately determine the results. Finally, using a specific anti-mine system as an example, we verified the validity and feasibility of the model by comparing it with the traditional method. The results demonstrate that the improved two-dimensional cloud model can overcome the ambiguity and randomness of data in cost risk assessment and can provide a reference for other scientific research projects of the same type.
Non-invasive HER2 detection in ovarian and breast cancer xenografts with 99m Tc-(HE) 3 Z HER2:V2
Authors: Hu Xianwen , Hu Hongyu , Li Dandan , Wang Pan , Cai Jiong
Published: January 2024

Purpose
To prepare a HER2 affibody molecular probe with high stability, high labeling yield, and easy radionuclide 99mTc labeling, we performed examinations on the biodistribution, determinated the bioactivity, conducted SPECT static imaging, and used other methods explore the potential of targeted HER2 receptor imaging of SKOV3 ovarian cancer and MDA-MB-361 breast cancer xenografts.
Methods
Affibody moleculars were produced by genetic recombination expression. The radiochemical purity of the 99mTc labeled HER2 affibody were identified by reverse phase high performance liquid chromatography (RP-HPLC). SKOV3 ovarian cancer cells and MDA-MB-361 breast cancer cells (HER2-positive) were subjected to evaluation of their affinity to HER2 by determining the equilibrium dissociation constants. The biodistribution of the 99mTc-labeled affibody molecular probe was then determined in Balb/c mice bearing SKOV3 tumors. Tumor targeting was assessed in the Balb/c mice using SKOV3, MDA-MB-361 and AT-3 (HER2-negative) xenografts.
Results
Affibody (HE)3ZHER2:V2 can be obtained by recombinant gene expression, which can be labeled with 99mTc and the radiolabeled molecular probe was identified by RP-HPLC to have a radiochemical purity of 96%. 99mTc-(HE)3ZHER2:V2 using RP-HPLC analysis showed that the radiochemical purity was 96%. The biodistribution study revealed that 99mTc-(HE)3ZHER2:V2 quickly bound to HER2-positive tumors after entering the circulatory system, and was cleared mainly through the urinary system. The HER2-positive SKOV3 and MDA-MB-361 nude mouse model was then subjected to single-photon emission computed tomography (SPECT) imaging 1–3 hours after the administration of an intravenous injection of 99mTc-(HE)3ZHER2:V2 through the tail vein, and the targeted uptake of the molecular probe by the tumor could be seen.
Conclusions
The molecular probe 99mTc-(HE)3ZHER2:V2 that we prepared in this work can be used to target specifically HER2 for imaging of HER2 positive SKOV3 and MDA-MB-361 xenografts in vivo. It is cleared out from the blood quickly, with no obvious toxic side effects. Therefore, 99mTc-(HE)3ZHER2:V2 is a promising marker for the detection of HER2 expression in tumor cells.
Lime amendment to chronically acidified forest soils results in shifts in prokaryotic and fungal communities.
Authors: Hosmer Maggie , Wright Robyn , McCavour Caitlin , Keys Kevin , Sterling Shannon , Langille Morgan , Rohde John
Published: January 2024

A consequence of past acid rain events has been chronic acidification of both Nova Scotian forests and watersheds, leading to a loss of essential nutrients and subsequently to decreased forest productivity and biodiversity. Liming – supplementing forests with crushed rock (dolomite, limestone, or basalt) – can restore essential nutrients to acidified soils as well as increasing the pH of the soils and the carbon capture by forests by promotion of tree growth. The effectiveness of liming treatments have often been assessed biologically through tree growth measurements, but microorganisms respond rapidly to changes in pH and nutrient availability, and would potentially provide early insights into forest recovery. However, the impact of liming on the soil microbiome is not well understood; understanding the impacts of liming on a micro as well as a macro level will help to determine whether liming is a good remediation strategy for Nova Scotia. A pilot study evaluating liming in acidified forests in Nova Scotia began in 2017. Microbiome analyses (prokaryotic 16S rRNA and fungal ITS2 gene amplicon sequencing) of three different depths (horizons) of soil show significant differences between lime-treated and control soils for the prokaryotic but not fungal communities, particularly in the uppermost soil horizon sampled. Notably, several genera, particularly from the Bacteroidia class, were significantly more abundant in treated than control soils in both upper soil horizons. The impacts of liming treatment were smaller in the deepest soil horizon sampled, suggesting that lime amendment either takes longer to reach these depths, or has little impact on these microbial communities. Future studies that investigate the functional capacity of these microbial communities and longitudinal follow-ups are warranted.
A Five-Year Survival Analysis of Breast Cancer Patients Post-Mastectomy at Muhimbili National Hospital
Authors: Mghase Adelaida , Brighton Meshack , Moshiro Candida , Kweka Walter , Mbembati Naboth
Published: January 2024

Background
In 2018, breast cancer, the leading malignancy in women, had nearly two million global diagnoses. While still a major cause of female fatalities, recent years have seen improved outlooks, with 5-year survival rates at 90% and 10-year survival at 80%. Western nations excel in early detection and personalized treatments. However, the increasing number of survivors necessitates focused strategies for post-treatment effects. This study focuses on addressing survivorship concerns in Tanzania by advocating for a comprehensive approach. The primary objective was to evaluate the five-year survival rates of patients undergoing mastectomy procedures.
Methods
This retrospective cohort study in Dar es Salaam gathered data from 337 patient files at Muhimbili National Hospital and records from the Ocean Road Cancer Institute. All patient records were included, regardless of co-morbidities, performance status, breast cancer details, and treatment methods. Five-year survival was calculated using the Kaplan-Meier method, and survival factors were analyzed with the Cox proportional hazards mode.
Results
Out of 337 mastectomy patients, 139 (41.2%) were aged 46–60. Overall, the five-year survival for 204 stage II and III patients, excluding stage IV cases, was 66% (95% CI = 54–75%). Stage II had an 84% survival rate, while stage III had 65%. The common surgeries were modified radical mastectomy (MRM) and total mastectomy. The main adjuvant therapies were chemotherapy (43.4%), hormonal therapy (36.0%), and radiotherapy (18.5%). Age, grade, and disease stage significantly predicted post-mastectomy breast cancer survival.
Conclusion
High survival rates are seen in early-stage breast cancer. Patient age and tumor grade impact survival. Common surgeries included MRM and total mastectomy, followed by various adjuvant therapies such as chemotherapy, hormonal treatment, radiotherapy, and immunotherapy.
Effects of Strip Intercropping of Coffee (Coffea arabica L.) with Groundnut (Arachis hypogaea L.) on Yield and Yield Advantage
Authors: Wegari Adisu , Girma Sintayehu , Gamachu Alamisa , Kasim Ibrahim
Published: January 2024

There are several advantages to intercropping over mono-cropping production. Therefore, intercropping approaches need to be investigated in greater depth. In order to evaluate the yield advantage, nutrient use efficiency, etc., of strip intercropping, researchers have proposed an intercropping approach that is based on systematic evaluation. Due to these advantages, intercropping is common throughout the world, especially in developing countries like Ethiopia. A field experiment was conducted at Mechara Agriculture Research center during 2016 to 2022 to evaluate the effect of strip intercropping ratios of coffee with groundnut on the yield of both crops and to determine economically optimum coffee to groundnut strip intercropping ratio for the study area. The experiment was laid out in a randomized complete block design with three replications. Coffee variety (Arusa) and Babble-1 groundnut variety were used. In the experiment, five treatments were applied: sole coffee, sole groundnut, 1:1, 1:2, and 1:3 ratios of coffee with groundnut. Regarding strip intercropping treatments, numerically the highest and lowest clean coffee yield was recorded at 1C (1coffee):3G (3goundnut) (9.79 * 100kg ha-1) and 1C (coffee): 2G (2groundnu) (8.53*100 kg ha-1) treatments. In coffee-groundnut strip intercropping, the highest land equivalent ratio was recorded at 1C (1coffee):3G (3goundnut) (1.68) closely followed by 1C (coffee): 2G (2groundnu) (1.43), and 1C (1coffee):1G (1groundnut) (1.39), which provides a relative yield advantage of 39 to 68%. As a result, the highest total LER indicates that strip intercropping with groundnut at 1C (1coffee):3G (3goundnut) ratio yields the highest yield and yield profit to farmers.
Oxidative Stress Index and Peripheral Biomarkers for Schizophrenia: A Revisited Approach.
Authors: Wasti Afshan Zeeshan , Jabeen Farah , Rasheed Shahana , Shah Nayab , Khan Dania , Zehra Zartaj , Aziz Farah , Riaz Aliya , Ahmed Sana , Ahmed Nikhat , Memon Anjuman Gul
Published: January 2024

Aims: Mental health issuesremain challenging due to the current diagnostic criteria based on traditional approaches. Misdiagnosis in Schizophrenia is common for various reasons, including inconsistent knowledge about the patient's history, unstable and overlapping symptoms, and lack of experienced professionals. Oxidative stress or redox dysregulation and inflammation implicate behavioral alterations in Schizophrenia. This study aims to evaluate the role of peripheral biomarkers, particularly oxidants/antioxidants, and inflammatory markers, and their potential correlations with oxidative stress index (OSI) in Schizophrenia.
Methods: Multiple approaches were considered to measure serum lipid profile, leukocyte indices, C-Reactive Protein (CRP), Inflammatory markers, Paraoxonase 1 (PON1), total antioxidant/oxidant status (TAS/TOS), and oxidative stress index (OSI) in both schizophrenic patients and healthy individuals (n=50 each group) by using standardized statistical methods.
Results: Our results further validate the involvement of oxidative stress in Schizophrenia and suggest the applicability of the oxidative stress index as a biomarker with restraint, potentially yielding a more accurate diagnosis of Schizophrenia.
Conclusion: Oxidative stress and inflammation play complementary roles, especially in Schizophrenia. The oxidative stress index may be a potential tool for more accurately diagnosing Schizophrenia and other related parameters. Further studies must confirm these findings, particularly future research with a larger sample size.
Perinatal Risk Factors of Cardiovascular-Renal Outcome in former Extremely Low Birth Weight neonates
Authors: Colleman Marieke , Staessen Jan A. , Allegaert Karel , Raaijmakers Anke
Published: January 2024

Background
Former Extremely Low Birthweight (ELBW) neonates suffer from adverse renal and cardiovascular outcomes later in life. Less is known about additional perinatal risk factors and their similarity for these adverse outcomes.
Methods
We compared cardiovascular-renal outcome between ELBW children and controls, to find perinatal risk factors for poorer renal and cardiovascular outcome and to unveil associations between kidney function and blood pressure. This study included 93 ELBW children and 87 healthy controls. We measured cystatin C-based estimated glomerular filtration rate (eGFR) and blood pressure. Blood pressure and eGFR levels were compared between cases and controls. We subsequently investigated perinatal risk factors for adverse outcome amongst ELBW children.
Results
ELBW children have significantly higher blood pressure and lower eGFR. Elevated blood pressure did not correlate with perinatal characteristics. ELBW children with eGFR < 90 ml/min/1.73m2 were ventilated longer (17 vs. 9 days, p = 0.006), more frequently male (OR = 3.33, p = 0.055) and tended to suffer more from intraventricular hemorrhage (40% vs. 15.8%, p = 0.056). There was no association between blood pressure and kidney dysfunction.
Conclusions
Understanding risk profiles for unfavorable outcomes may help to identify children at increased risk for kidney or cardiac dysfunction. These risk profiles could be different for renal and cardiovascular outcome. Poorer eGFR was associated with longer ventilation, male sex, and intra-ventricular hemorrhage. This knowledge can lead to safer neonatal therapeutic regimens for ELBW infants, a more intensive follow-up and earlier treatment initiation for children at highest risk.