bluuebunny/crossref_metadata_2025 huggingface dataset:
Pengelolaan Penerimaan Peserta Didik Baru (PPDB) Ditinjau Dari Perspektif Total Quality Management (TQM) di Madrasah Bertaraf Internasional (MBI) Amanatul Ummah Pacet Mojokerto
Authors: Al Qorony Wais , Mujiono
Published: August 2024

Abstract— Educational institutions prioritize quality. With the emergence of competing schools, it becomes very important to identify schools that meet quality standards. The TQM integrated quality control system combines the efforts of developing, maintaining, and improving quality from all levels in an organizational group to increase productivity levels. To become a learner at an educational institution (madrasah), there must be registration of new learners, first a search process is carried out, then a recruitment process is carried out to identify prospective new learners and capture these prospective learners. The purpose of this research has been adjusted to the focus of the research, so that it is an effort to provide a comprehensive explanation and description:  1) To analyze the selection process of new student admissions at MBI Amanatul Ummah. 2) To analyze the implications of the selection process of new student admissions at MBI Amanatul Ummah. This research is a field study with a qualitative approach applied. In this study, various data collection techniques were used by researchers through the Observation method, Interview Method, Documentation Method. The results showed the results that 1) PPDb program planning at MBI Amanatul Ummah in its implementation, MBI leaders wait for direction from the foundation. 2) The PPDb committee is taken from the Functionalists, TU Staff, and Head of Class. The information media used are social media and the school website. 3) The tests tested in the written test path are academic potential tests and psychological tests. The achievement path is opened only for those who have a minimum certificate of district level champion, the test tested is an interview related to the certificate attached.
Key Words: Total Quality Management, New Student Registration
Responsiveness of alfalfa varieties to inoculation by nodule bacteria
Authors: Ionov Aleksey
Published: August 2024

Five new strains of alfalfa nodule bacteria and production strain 445a were evaluated. The high activity of a new strain III isolated from a suspension washed from alfalfa seeds of European origin was revealed. Pre-sowing inoculation with strain III increased the productivity of alfalfa plants of Pastbishchnaya 88 and Taisiya varieties by 23–44% and 18–61% in three out of six mowing. The positive effect of pre-sowing inoculation with new strains I, II, IV, V on the height (+4.7–9.5 cm) of Pastbishchnaya 88 plants in the third, fourth and fifth cycles, in the summer (June–August) was noted. The effect on height in plants of the Taisiya variety is not noted. The efficiency of symbiosis in the summer period during inoculation with strains I, II, IV, V was 105–127% in the Pastbishchnaya 88 variety and 101–150% in the Taisiya variety. A positive, high, linear correlation dependence of the productivity of alfalfa plants of Pastbishchnaya 88 and Taisiya varieties on their height was revealed.
Seed treatment: an alternative and sustainable approach to cotton seed delinting
Authors: Zahra Laviza Tuz , Qadir Fariha , Khan Mohammad Nasir , Kamal Hira , Zahra Nosheen , Ali Arfan , Zafar Muhammad Mubashar , Razzaq Abdul , Jiang Xuefei
Published: August 2024

This review article delves into the vital aspects of cotton, emphasizing its global significance as a crucial agricultural commodity. The paper comprehensively explores the composition of cotton and surveys the diverse methods employed for the removal of cotton lint from seeds. Conventional delinting methods, including mechanical and chemical approaches, are scrutinized in terms of their advantages and drawbacks. However, the primary focus of this review is on highlighting the emerging significance of biological delinting methods. By harnessing the power of microbial enzymes and organisms, biological approaches offer a promising alternative for efficient lint removal. The authors discuss the environmental advantages associated with biological delinting, positioning it as a sustainable solution that mitigates the ecological impact of traditional methods. Furthermore, the article contextualizes these delinting methods within the framework of Sustainable Development Goals (SDGs) and underscores the importance of adopting eco-friendly practices in the cotton industry to align with SDG goals. By accentuating the potential of biological delinting in contributing to sustainable agriculture and responsible production, the review advocates for a paradigm shift towards more environmentally conscious approaches in the cotton sector. Overall, the article aims to provide a comprehensive perspective on cotton delinting methods, emphasizing the pivotal role of biological alternatives in fostering a sustainable and goal-oriented future for the cotton industry.
Generative artificial intelligence in chemical engineering spans multiple scales
Authors: Decardi-Nelson Benjamin , Alshehri Abdulelah S. , You Fengqi
Published: August 2024

Recent advances in generative artificial intelligence (GenAI), particularly large language models (LLMs), are profoundly impacting many fields. In chemical engineering, GenAI plays a pivotal role in the design, scale-up, and optimization of chemical and biochemical processes. The natural language understanding capabilities of LLMs enable the interpretation of complex chemical and biological data. Given the rapid developments of GenAI, this paper explores the extensive applications of GenAI in multiscale chemical engineering, spanning from quantum mechanics to macro-level optimization. At quantum and molecular levels, GenAI accelerates the discovery of novel products and enhances the understanding of fundamental phenomena. At larger scales, GenAI improves process design and operational efficiency, contributing to sustainable practices. We present several examples to demonstrate the role of GenAI, including its impact on nanomaterial hardness enhancement, novel catalyst generation, protein design, and the development of autonomous experimental platforms. This multiscale integration demonstrates the potential of GenAI to address complex challenges, drive innovation, and foster advancements in chemical engineering.
Proteomics and phosphoproteomics reveal novel proteins involved in Cipangopaludina chinensis carcasses
Authors: Liu Gongzhen , Zhong Kangyu , Gong Shanmin , Li Xinru , Li Yanshen
Published: August 2024

Cipangopaludina chinensis is a common freshwater mollusk that is widely distributed worldwide, especially in China. In our research, 1,382 proteins and 1,039 phosphorylated proteins were identified from C. chinensis carcasses, and 690 differentially expressed proteins (DEPs) were quantified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the DEPs are involved in cellular processes, single-organism processes, metabolic processes, developmental processes, localization, and biological regulation. The phosphorylated proteins were found to be related to the Rap1 signaling pathway, Ras signaling pathway, calcium signaling pathway, and longevity-regulating pathways. Moreover, we also identified important regulatory enzymes, such as guanylate cyclase, tyrosine protein kinase, receptor protein tyrosine kinase, and glyoxylate reductase/hydroxypyruvate reductase. Notably, we found guanylate cyclase to be present in multiple signaling pathways, including the Rap1 signaling pathway, calcium signaling pathway, Ras signaling pathway, insulin secretion, longevity regulating pathway, glutamatergic synapse, circadian entrainment, and gap junction. This enzyme may play a crucial role in regulating molecular mechanisms in C. chinensis. In summary, proteomic and phosphoproteomic analyses of C. chinensis carcasses displayed significant differences among different geographical isolates, which helps enhance our understanding of food nutrition, signaling pathways, and metabolic mechanisms in C. chinensis.
Synergistic in vitro activity and mechanism of KBN lotion and miconazole nitrate against drug-resistant Candida albicans biofilms
Authors: Cao Xiaoyu , Xiao Ni , Huang Jingyi , Li Li , Zhong Lian , Zhang Jun , Wang Fengyun
Published: August 2024

Background

In the face of increasing antifungal resistance among Candida albicans biofilms, this study explores the efficacy of a combined treatment using Kangbainian lotion (KBN) and miconazole nitrate (MN) to address this challenge.

Methods

Using UPLC-Q-TOF/MS Analysis for Identification of Active Compounds in KBN Lotion; FICI for synergy evaluation, XTT and ROS assays for biofilm viability and oxidative stress, fluorescence and confocal laser scanning microscopy (CLSM) for structural and viability analysis, and real-time fluorescence for gene expression.

Conclusion

Our study indicates that the combined application of KBN and MN somewhat impacts the structural integrity of Candida albicans biofilms and affects the expression of several key genes involved in biofilm formation, including ALS1, ALS3, HWP1, HSP90, and CSH1. These preliminary findings suggest that there may be a synergistic effect between KBN and MN, potentially influencing not only the structural aspects of fungal biofilms but also involving the modulation of genetic pathways during their formation.
Age-specific performance of human papillomavirus E6/E7 mRNA assay versus cytology for primary cervical cancer screening and triage: community-based screening in China
Authors: Zhang Jing , Liu Guangcong , Yang Di , Cui Xiaoli , Wang Chunyan , Wang Danbo , Piao Haozhe
Published: August 2024

Background

In the general population, primary human papillomavirus (HPV) testing is advocated for cervical cancer (CC) screening. HPV E6/E7 mRNA (Aptima HPV, AHPV) assays have garnered considerable traction due to their higher specificity when compared with HPV DNA assays. Here, we investigated age-specific primary AHPV screening assays and different triage strategies versus cytology to identify the best approach.

Methods

Between April 2018 and December 2021, we recruited female participants from 34 communities across Liaoning province and Qingdao City, China. Primary cervical screening protocols included liquid-based cytology (LBC) and AHPV assays, with females positive for any assays undergoing colposcopy. Genotyping (AHPV-GT) was conducted on all HPV-positive samples. Our primary outcomes were the identification of age-specific detection rates, colposcopy referral rates, and sensitivity and specificity values for high-grade squamous intraepithelial lesions or worse (HSIL+). AHPV and different triage strategy performances were also examined across different age cohorts.

Results

Our investigation included 9911 eligible females. Age-specific abnormal cytology rates were in the 6.1%–8.0% range, and were highest in 45–54-year olds. When compared with 35–44-or 45–54-year olds, HPV prevalence was highest in 55–64-year olds (12.2% or 11.6% vs.14.1%, P = 0.048 and P = 0.002, respectively). In 35–44-year olds, AHPV sensitivity for detecting HSIL+ was 96.6 (95% confidence interval [CI]: 89.7–100) - significantly higher than LBC sensitivity (65.5 [95% CI: 48.3–82.8], P < 0.001). When compared with LBC, HSIL+ detection rates by AHPV-GT using reflex LBC triage increased by 31.5% (9.6‰ vs. 7.3‰), and colposcopy referral rates decreased by 16.4% (5.1% vs. 6.1%). In 45–54-year olds, HSIL+ detection rates for AHPV-GT using reflex LBC triage were lower than LBC rates (6.2‰ vs. 6.6‰). In 55–64-year olds, AHPV sensitivity (97.2 [95% CI: 91.7–100.0]) was higher than LBC sensitivity (66.7 [95% CI: 50.0–80.6], P = 0.003). The area under the curve (AUC) value was not significantly different between AHPV-GT with reflex LBC triage and LBC (0.845 [95% CI: 0.771–0.920] vs. 0.812 [95% CI: 0.734–0.891], P = 0.236).

Conclusions

Primary AHPV screening using different triage strategies were different across different age cohorts. Thus, AHPV may be an appropriate primary screening method for 35–44 and 55–64 year old females, while AHPV-GT with reflex LBC triage may be more apt for 35–44 year old females.
The relationship between self-assessment of language proficiency and measures of lexical diversity and syntactic complexity: evidence from bilingual speakers of Italian in Croatia
Authors: Hržica Gordana , Košutar Sara , Poropat Jeletić Nada
Published: August 2024

A wide range of tools have been used to assess the language proficiency of bilingual speakers. The validity and high reliability of lexical diversity and syntactic complexity measures as instruments for measuring language proficiency have been demonstrated in previous studies across different languages. However, the relationship between self-assessment and the two measures has not yet been investigated. The present study focused on the Italophone bilingual language speakers, an understudied minority diglossic community in Croatia, and investigated whether measures of lexical diversity and syntactic complexity reflect self-assessment of language proficiency in the standard Italian language and the Istrovenetian dialect overall and in four specific domains (reading, writing, speaking, and listening). In addition, we aimed to investigate whether there are possible differences in self-assessment between the standard Italian language and the Istrovenetian dialect and whether there are language variety-related differences (standard vs. dialect) in the relationship between self-assessment and measures of lexical diversity and syntactic complexity. The results showed an intricate interplay between self-assessment and the lexical diversity and syntactic complexity of bilingual speech. This suggests that these measures are interrelated and that heritage bilingual language speakers may be able to objectively assess their language proficiency.
Exploring the shared biomarkers between cardioembolic stroke and atrial fibrillation by WGCNA and machine learning
Authors: Zhang Jingxin , Zhang Bingbing , Li Tengteng , Li Yibo , Zhu Qi , Wang Xiting , Lu Tao
Published: August 2024

Background

Cardioembolic Stroke (CS) and Atrial Fibrillation (AF) are prevalent diseases that significantly impact the quality of life and impose considerable financial burdens on society. Despite increasing evidence of a significant association between the two diseases, their complex interactions remain inadequately understood. We conducted bioinformatics analysis and employed machine learning techniques to investigate potential shared biomarkers between CS and AF.

Methods

We retrieved the CS and AF datasets from the Gene Expression Omnibus (GEO) database and applied Weighted Gene Co-Expression Network Analysis (WGCNA) to develop co-expression networks aimed at identifying pivotal modules. Next, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the shared genes within the modules related to CS and AF. The STRING database was used to build a protein-protein interaction (PPI) network, facilitating the discovery of hub genes within the network. Finally, several common used machine learning approaches were applied to construct the clinical predictive model of CS and AF. ROC curve analysis to evaluate the diagnostic value of the identified biomarkers for AF and CS.

Results

Functional enrichment analysis indicated that pathways intrinsic to the immune response may be significantly involved in CS and AF. PPI network analysis identified a potential association of 4 key genes with both CS and AF, specifically PIK3R1, ITGAM, FOS, and TLR4.

Conclusion

In our study, we utilized WGCNA, PPI network analysis, and machine learning to identify four hub genes significantly associated with CS and AF. Functional annotation outcomes revealed that inherent pathways related to the immune response connected to the recognized genes might could pave the way for further research on the etiological mechanisms and therapeutic targets for CS and AF.
Risk prediction model for in-stent restenosis following PCI: a systematic review
Authors: Xiang Qin , Xiong Xiao-Yun , Liu Si , Zhang Mei-Jun , Li Ying-Jie , Wang Hui-Wen , Wu Rui , Chen Lu
Published: August 2024

Introduction

The morbidity and mortality rates of coronary heart disease are significant, with PCI being the primary treatment. The high incidence of ISR following PCI poses a challenge to its effectiveness. Currently, there are numerous studies on ISR risk prediction models after PCI, but the quality varies and there is still a lack of systematic evaluation and analysis.

Methods

To systematically retrieve and evaluate the risk prediction models for ISR after PCI. A comprehensive search was conducted across 9 databases from inception to March 1, 2024. The screening of literature and extraction of data were independently carried out by two investigators, utilizing the checklist for critical appraisal and data extraction for systematic reviews of prediction modeling studies (CHARMS). Additionally, the risk of bias and applicability were evaluated using the Prediction Model Risk of Bias Assessment Tool (PROBAST).

Results

A total of 17 studies with 29 models were included, with a sample size of 175–10,004 cases, and the incidence of outcome events was 5.79%–58.86%. The area under the receiver operating characteristic curve was 0.530–0.953. The top 5 predictors with high frequency were diabetes, number of diseased vessels, age, LDL-C and stent diameter. Bias risk assessment into the research of the risk of higher bias the applicability of the four study better.

Discussion

The overall risk of bias in the current ISR risk prediction model post-PCI is deemed high. Moving forward, it is imperative to enhance study design and specify the reporting process, optimize and validate the model, and enhance its performance.
Epicardial pulsed-field ablation-impact of electric field and heat distribution induced by coronary metallic stents
Authors: Wang Zhen , Liang Ming , Sun Jingyang , Zhang Jie , Li Yunhao , Xu Lisheng , Han Yaling
Published: August 2024

Background

Pulsed-field ablation (PFA) technique is a nonthermal ablation technique. No study has yet evaluated the effect of the positional relationship between the ablation electrode (AE) and the coronary metal stent (CMS) on the electric field distribution and temperature distribution in epicardial ablation. Our study aimed to evaluate the effect of the CMS on the electric field as well as the temperature distribution in different models.

Methods

Multi-angle modeling of the CMS and AE was performed. The PFA ablation region was evaluated with a field strength contour of 1,000 V/cm, which was used to assess the validity of the two-dimensional (2D) model simulation data as well as the distribution of the multi-angle electric field and temperature in the three-dimensional (3D) model.

Results

The presence of the CMS had little effect on the width of the ablation area (0.2 mm). In the 3D model, the temperature of the ablation area was highest when the angle between the AE and the CMS was in the 90° position (43.4°C, 41.3°C); a change in the distance between the AE and the CMS affected the temperature of the ablation area (maximum 2.1°C) and the width of the ablation (maximum 0.32 mm).

Conclusion

The presence of the CMS distorts the distribution of the electric field, but does not produce a change in the extent of the ablation damage, nor does it bring thermal damage to the ablation region. Different simulation models give similar results in PFA calculations, and this study effectively reduces the complexity of modeling simulation.
A self-supervision rockburst risk prediction algorithm based on automatic mining of rockburst prediction index features
Authors: Zhang Xiufeng , Zhang Haikuan , Li Haitao , Li Guoying , Xue Shanshan , Yin Haichen , Chen Yang , Han Fei
Published: August 2024

The rockburst risk prediction based on microseismic (MS) data is an important research task in deep mine safety prevention. However, the lack of systematic research on explicit prediction indexes and the waste of a large amount of unlabeled data are still two main problems that hinder the development of rockburst prediction. In this paper, the acoustic emission (AE) event distribution at each coal rock deformation and failure stage is studied based on the laboratory experiment. The spatial-temporal evolution of rockburst in MS data of coal mine fields is explored. Based on systematic research of the AE and MS distribution features considering the physical logic of coal rock mass failure, nine different rockburst prediction indexes are employed to describe the MS data features before rockburst. Then, according to the rockburst prediction indexes, a new self-supervision rockburst risk prediction algorithm is constructed, consisting of the pre-trained model and fine-tuning model with the same encoder and decoder structure. The pre-trained model is trained with unlabeled MS data to automatically learn rockburst prediction index features by reconstructing the masked indexes. Based on the pre-trained encoder and decoder parameters, the fine-tuning model is trained with the labeled MS data to predict rockburst risk. A large number of experiments show that the proposed rockburst prediction self-supervision algorithm is far superior to previous algorithms, by effectively utilizing unlabeled data. The ablation experiment also proves the validity of the studied rockburst prediction indexes.
MRGS-LSTM: a novel multi-site wind speed prediction approach with spatio-temporal correlation
Authors: Zhou Yueguang , Fan Xiuxiang
Published: August 2024

The wind energy industry is witnessing a new era of extraordinary growth as the demand for renewable energy continues to grow. However, accurately predicting wind speed remains a significant challenge due to its high fluctuation and randomness. These difficulties hinder effective wind farm management and integration into the power grid. To address this issue, we propose the MRGS-LSTM model to improve the accuracy and reliability of wind speed prediction results, which considers the complex spatio-temporal correlations between features at multiple sites. First, mRMR-RF filters the input multidimensional meteorological variables and computes the feature subset with minimum information redundancy. Second, the feature map topology is constructed by quantifying the spatial distance distribution of the multiple sites and the maximum mutual information coefficient among the features. On this basis, the GraphSAGE framework is used to sample and aggregate the feature information of neighboring sites to extract spatial feature vectors. Then, the spatial feature vectors are input into the long short-term memory (LSTM) model after sliding window sampling. The LSTM model learns the temporal features of wind speed data to output the predicted results of the spatio-temporal correlation at each site. Finally, through the simulation experiments based on real historical data from the Roscoe Wind Farm in Texas, United States, we prove that our model MRGS-LSTM improves the performance of MAE by 15.43%–27.97% and RMSE by 12.57%–25.40% compared with other models of the same type. The experimental results verify the validity and superiority of our proposed model and provide a more reliable basis for the scheduling and optimization of wind farms.
Radiomics-based machine learning model to phenotype hip involvement in ankylosing spondylitis: a pilot study
Authors: Hu Zhengyuan , Wang Yan , Ji Xiaojian , Xu Bo , Li Yan , Zhang Jie , Liu Xingkang , Li Kunpeng , Zhang Jianglin , Zhu Jian , Lou Xin , Huang Feng
Published: August 2024

Objectives

Hip involvement is an important reason of disability in patients with ankylosing spondylitis (AS). Unveiling the potential phenotype of hip involvement in AS remains an unmet need to understand its biological mechanisms and improve clinical decision-making. Radiomics, a promising quantitative image analysis method that had been successfully used to describe the phenotype of a wide variety of diseases, while it was less reported in AS. The objective of this study was to investigate the feasibility of radiomics-based approach to profile hip involvement in AS.

Methods

A total of 167 patients with AS was included. Radiomic features were extracted from pelvis MRI after image preprocessing and feature engineering. Then, we performed unsupervised machine learning method to derive radiomics-based phenotypes. The validation and interpretation of derived phenotypes were conducted from the perspectives of clinical backgrounds and MRI characteristics. The association between derived phenotypes and radiographic outcomes was evaluated by multivariable analysis.

Results

1321 robust radiomic features were extracted and four biologically distinct phenotypes were derived. According to patient clinical backgrounds, phenotype I (38, 22.8%) and II (34, 20.4%) were labelled as high-risk while phenotype III (24, 14.4%) and IV (71, 42.5%) were at low risk for hip involvement. Consistently, the high-risk phenotypes were associated with higher prevalence of MRI-detected lesion than the low-risk. Moreover, phenotype I had significant acute inflammation signs than phenotype II, while phenotype IV was enthesitis-predominant. Importantly, the derived phenotypes were highly predictive of radiographic outcomes of patients, as the high-risk phenotypes were 3 times more likely to have radiological hip lesion than the low-risk [27 (58.7%) vs 16 (28.6%); adjusted odds ratio (OR) 2.95 (95% CI 1.10, 7.92)].

Conclusion

We confirmed for the first time, the clinical actionability of profiling hip involvement in AS by radiomics method. Four distinct phenotypes of hip involvement in AS were identified and importantly, the high-risk phenotypes could predict structural damage of hip involvement in AS.
Decoding the secret of extracellular vesicles in the immune tumor microenvironment of the glioblastoma: on the border of kingdoms
Authors: Ghazi Bouchra , Harmak Zakia , Rghioui Mounir , Kone Abdou-Samad , El Ghanmi Adil , Badou Abdallah
Published: August 2024

Over the last decades, extracellular vesicles (EVs) have become increasingly popular for their roles in various pathologies, including cancer and neurological and immunological disorders. EVs have been considered for a long time as a means for normal cells to get rid of molecules it no longer needs. It is now well established that EVs play their biological roles also following uptake or by the interaction of EV surface proteins with cellular receptors and membranes. In this review, we summarize the current status of EV production and secretion in glioblastoma, the most aggressive type of glioma associated with high mortality. The main purpose is to shed light on the EVs as a universal mediator of interkingdom and intrakingdom communication in the context of tumor microenvironment heterogeneity. We focus on the immunomodulatory EV functions in glioblastoma-immune cross-talk to enhance immune escape and reprogram tumor-infiltrating immune cells. We critically examine the evidence that GBM-, immune cell-, and microbiome-derived EVs impact local tumor microenvironment and host immune responses, and can enter the circulatory system to disseminate and drive premetastatic niche formation in distant organs. Taking into account the current state of the art in intratumoral microbiome studies, we discuss the emerging role of bacterial EV in glioblastoma and its response to current and future therapies including immunotherapies.
Human papillomavirus disease in GATA2 deficiency: a genetic predisposition to HPV-associated female anogenital malignancy
Authors: Dancy Ehren , Stratton Pamela , Pichard Dominique C. , Marciano Beatriz E. , Cowen Edward W. , McBride Alison A. , Van Doorslaer Koenraad , Merideth Melissa A. , Salmeri Noemi , Hughes Marybeth S. , Heller Theo , Parta Mark , Hickstein Dennis D. , Kong Heidi H. , Holland Steven M. , Zerbe Christa S.
Published: August 2024

Objective

Patients with pathogenic variants in the GATA Binding Protein 2 (GATA2), a hematopoietic transcription factor, are at risk for human papillomavirus-related (HPV) anogenital cancer at younger than expected ages. A female cohort with GATA2 haploinsufficiency was systematically assessed by two gynecologists to characterize the extent and severity of anogenital HPV disease, which was also compared with affected males.

Methods

A 17-year retrospective review of medical records, including laboratory, histopathology and cytopathology records was performed for patients diagnosed with GATA2 haploinsufficiency followed at the National Institutes of Health. Student’s t-test and Mann-Whitney U test or Fisher’s exact test were used to compare differences in continuous or categorical variables, respectively. Spearman’s rho coefficient was employed for correlations.

Results

Of 68 patients with GATA2 haploinsufficiency, HPV disease was the initial manifestation in 27 (40%). HPV occurred at median 18.9 (15.2-26.2) years in females, and 25.6 (23.4-26.9) years in males. Fifty-two (76%), 27 females and 25 males, developed HPV-related squamous intraepithelial lesions (SIL) including two males with oral cancer. Twenty-one patients developed anogenital high-grade SIL (HSIL) or carcinoma (16 females versus 5 males, (59% versus 20%, respectively, p=0.005) at median 27 (18.6-59.3) years for females and 33 (16.5-40.1) years for males. Females were more likely than males to require >2 surgeries to treat recurrent HSIL (p=0.0009). Of 30 patients undergoing hematopoietic stem cell transplant (HSCT) to manage disease arising from GATA2 haploinsufficiency, 12 (nine females, three males) had persistent HSIL/HPV disease. Of these nine females, eight underwent peri-transplant surgical treatment of HSIL. Five of seven who survived post-HSCT received HPV vaccination and had no or minimal evidence of HPV disease 2 years post-HSCT. HPV disease persisted in two receiving immunosuppression. HPV disease/low SIL (LSIL) resolved in all three males.

Conclusion

Females with GATA2 haploinsufficiency exhibit a heightened risk of recurrent, multifocal anogenital HSIL requiring frequent surveillance and multiple treatments. GATA2 haploinsufficiency must be considered in a female with extensive, multifocal genital HSIL unresponsive to multiple surgeries. This population may benefit from early intervention like HSCT accompanied by continued, enhanced surveillance and treatment by gynecologic oncologists and gynecologists in those with anogenital HPV disease.
Plasma concentrations of IL-6, MIP-1β, IP-10, and PTX-3 as predictors of the immunological response to antiretroviral treatment in people with HIV
Authors: Mejías-Trueba Marta , Saborido-Alconchel Abraham , Serna-Gallego Ana , Trujillo-Rodríguez María , Muñoz-Muela Esperanza , Llaves-Flores Silvia , Espinosa Nuria , Roca-Oporto Cristina , Herrero Marta , Sotomayor Cesar , López-Cortes Luis F.
Published: August 2024

Despite effective antiretroviral therapy (ART), 15-30% of people with HIV experience poor CD4+ T-cell recovery, termed immunologic non-responders (INR). This study aims to evaluate whether pre-ART plasma levels of interleukin-6 (IL-6), interferon gamma-induced protein-10 (IP-10), macrophage inflammatory protein-1-β (MIP-1β), and/or pentraxin-3 (PTX-3) could predict subsequent immunologic recovery. Seventy-four participants were enrolled and classified as INR and immunologic responders (IR) based on CD4+/CD8+ ratio increase over 24 months after starting ART. The results showed no significant differences in cytokine levels between INR and IR. Therefore, IL-6, IP-10, MIP-1β, and PTX-3 were unsuitable as predictive markers of poor immune recovery.
Bispecific killer cell engagers employing species cross-reactive NKG2D binders redirect human and murine lymphocytes to ErbB2/HER2-positive malignancies
Authors: Pfeifer Serrahima Jordi , Schoenfeld Katrin , Kühnel Ines , Harwardt Julia , Macarrón Palacios Arturo , Prüfer Maren , Kolaric Margareta , Oberoi Pranav , Kolmar Harald , Wels Winfried S.
Published: August 2024

NKG2D is an activating receptor expressed by natural killer (NK) cells and other cytotoxic lymphocytes that plays a pivotal role in the elimination of neoplastic cells through recognition of different stress-induced cell surface ligands (NKG2DL). To employ this mechanism for cancer immunotherapy, we generated NKG2D-engaging bispecific antibodies that selectively redirect immune effector cells to cancer cells expressing the tumor-associated antigen ErbB2 (HER2). NKG2D-specific single chain fragment variable (scFv) antibodies cross-reactive toward the human and murine receptors were derived by consecutive immunization of chicken with the human and murine antigens, followed by stringent screening of a yeast surface display immune library. Four distinct species cross-reactive (sc) scFv domains were selected, and reformatted into a bispecific engager format by linking them via an IgG4 Fc domain to a second scFv fragment specific for ErbB2. The resulting molecules (termed scNKAB-ErbB2) were expressed as disulfide-linked homodimers, and demonstrated efficient binding to ErbB2-positive cancer cells as well as NKG2D-expressing primary human and murine lymphocytes, and NK-92 cells engineered with chimeric antigen receptors derived from human and murine NKG2D (termed hNKAR and mNKAR). Two of the scNKAB-ErbB2 molecules were found to compete with the natural NKG2D ligand MICA, while the other two engagers interacted with an epitope outside of the ligand binding site. Nevertheless, all four tested scNKAB-ErbB2 antibodies were similarly effective in redirecting the cytotoxic activity of primary human and murine lymphocytes as well as hNKAR-NK-92 and mNKAR-NK-92 cells to ErbB2-expressing targets, suggesting that further development of these species cross-reactive engager molecules for cancer immunotherapy is warranted.
Evaluating the efficacy and safety of different neoadjuvant immunotherapy combinations in locally advanced HNSCC: a systematic review and meta-analysis
Authors: Liu Chang , Li Mingzhu , Liu Xiaojie , Shi Ting , Wang Yun , Sui Chaoyang , Zhang Wenan , Wang Bowen
Published: August 2024

Background

Immune checkpoint inhibitors have demonstrated promising therapeutic outcomes in recurrent/metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC), prompting numerous clinical trials to investigate the safety and efficacy of this approach in neoadjuvant therapy. This systematic review aims to consolidate and analyze the findings from various clinical trials combining neoadjuvant immunotherapy for HNSCC, with the goal of identifying the most effective neoadjuvant immunotherapy regimen.

Methods

The system conducted searches across electronic databases including PubMed, Embase, the Cochrane Library and Web of science from their inception to July 1, 2024. The primary focus was on evaluating efficacy (particularly pathological complete response (pCR), major pathological response (MPR), and overall response rate (ORR)) and safety (primarily assessed by grade 3-4 treatment-related adverse reactions).

Results

A total of 1943 patients from 32 studies were analyzed. Combining neoadjuvant immunotherapy with chemotherapy or radiotherapy demonstrated superiority over neoadjuvant immunotherapy alone in terms of the MPR rate, while showing no statistically significant difference in the pCR rate. Furthermore, the combination of neoadjuvant immunotherapy with chemotherapy or radiotherapy exhibited a lower CR rate compared to neoadjuvant immunotherapy with radiotherapy alone, but a higher PR rate and SD rate. Apart from the neoadjuvant immunotherapy group in isolation, there were no statistically significant differences in grade ≥3 treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) among the other three combination therapy groups.

Conclusion

This systematic review and meta-analysis indicate that patients with locally advanced HNSCC might benefit from neoadjuvant immunotherapy, particularly when used in conjunction with chemotherapy or radiotherapy. Nonetheless, additional data is required to definitively confirm its efficacy.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=553753, identifier CRD42024553753.
Cancellation of the more complicated ophthalmic inpatient surgeries in a tertiary general hospital: a 10-year retrospective study
Authors: Zhao Xinyu , Zhao Qing , Wu Yanfang , Cheng Shiyu , Wang Chuting , Meng Lihui , Gu Xingwang , Chen Youxin
Published: August 2024

Background

Although ophthalmic ambulatory surgeries are less costly and may enhance the more efficient utilization of hospital resources, inpatient surgeries were preferable alternatives for patients with complicated eye diseases or poor general health. However, the incidence, causes, and related factors of ophthalmic inpatient surgery cancellation remained largely unknown.

Methods

The electronic medical records of ophthalmic inpatient surgeries between January 2012 and December 2022 was retrospectively reviewed. Cancellation-related factors were explored using multivariate logistic regression analysis and the reasons of cancellation were also evaluated.

Results

In total, 820 cancelled surgeries and 42,073 performed surgeries were included, with a cancellation rate of 1.9%. Any other ocular comorbidities were risk factors for cancellation (odds ratio (OR) 1.872, 95% confidence intervals (CI) 1.504–2.331; p < 0.001), while older age (OR 0.990, 95% CI 0.986–0.995; p < 0.001), local residence (OR 0.809, 95% CI 0.692–0.947; p = 0.008), any systemic comorbidities (OR 0.740, 95% CI 0.616–0.889; p = 0.001), and previous history of surgeries (OR 0.403, 95% CI 0.341–0.476; p < 0.001) were negatively associated with surgery cancellation. The top two categorical cancellation reasons were medical factors (508, 62.0%) and patient-related factors (285, 34.8%). “Patient/family refused surgery” (127, 15.5%), “acute conjunctivitis or uveitis relapse” (103, 12.6%), and “ocular condition improved and procedure no longer indicated” (71, 8.7%) were the three most common single cancellation reasons.

Conclusion

Any other ocular comorbidities, younger age, no systemic comorbidities, non-local residence, and no past surgical history were related factors for ophthalmic inpatient surgery cancellation. The majority of cancellations were due to patient-related or medical factors. Great importance should be attached to the cancellation of the more complicated inpatient surgeries and further efforts are warranted to explore how to reduce cancellation.
Case report: Bruton tyrosine kinase inhibitor as therapy for chronic lymphocytic leukemia infiltrating a kidney allograft
Authors: Stavart Louis , Halfon Matthieu , Dewarrat Natacha , Rotman Samuel , Golshayan Dela
Published: August 2024

The burden of chronic lymphocytic leukemia (CLL) in the prognosis of solid organ transplant (SOT) recipients seems non-negligible. Whether transplanting a patient with previous CLL is safe or what is the optimal monitoring and treatment management after transplantation is still unclear and only based on few case series and reports. Therefore, we aimed to contribute to this understanding by reporting the first documented case of a clinically significant CLL with biopsy-proven infiltration of the kidney allograft and its successful management with a Bruton tyrosine kinase inhibitor (BTKi). We then reviewed the related literature, with a focus on CLL and kidney transplantation. Our main message is that BTKi may represent a safe and effective intervention to prevent the hazardous patient and graft outcomes of CLL in SOT patients.
Elucidation of mechanisms underlying active oxygen burst in Citrus sinensis after Diaporthe citri infection using transcriptome analysis
Authors: Liu Tiantian , Zhou Zehua , Luo Changwei , Luo Hua , Tang Jun , Shi Xiaojiang , Li Diping , Zhang Qiong , Li Jin , Xia Yonggang , Song Na , Yi Tuyong
Published: August 2024

Introduction

Reactive oxygen species (ROS) generation is a common disease defense mechanism in plants. However, it is unclear whether Citrus host activates defense response against Diaporthe citri causing citrus melanose disease by producing ROS, and the underlying molecular mechanisms are unknown.

Methods

DAB staining and RNA-Seq technology were used to compare the active oxygen burst and differential gene expression, respectively, in uninfected and infected Citrus sinensis leaves at different time points during D. citri infection in vivo. The functions of CsRBOH (a significant DEG) were confirmed in N. benthamiana through the Agrobacterium-mediated transient expression system.

Results

DAB staining indicated that C. sinensis initiated defense against D. citri infection within 24 h by generating ROS. Illumina sequencing revealed 25,557 expressed genes of C. sinensis. The most upregulated DEGs (n = 1,570) were identified 72 h after fungal inoculation (sample denoted as CD72). In the CD72 vs. Cs (samples at 0 h after fungal inoculation) comparison, the KEGG pathway category with the highest number of genes (n = 62) and most significant enrichment was Protein processing in endoplasmic reticulum, followed by Glutathione metabolism and MAPK signaling pathway-plant. GO analysis revealed that the DEGs of CD72 vs. Cs related to active oxygen burst and chitin recognition were significantly grouped into the regulation of biological processes and molecular functions, with GO terms including response to ROS, response to fungus, and oxidoreductase activity. Remarkably, CsRBOH was significantly enriched in the GO and KEGG analyses, and its expression pattern in qRT-PCR and DAB staining results were consistent. Among the 63 ROS-related DEGs, HSP genes and genes associated with the peroxidase family were highly significant as revealed by protein–protein interaction networks. Furthermore, ROS accumulation, cell death, and upregulation of defense-related genes were observed in N. benthamiana leaves with CsRBOH expressed through the Agrobacterium-mediated transient expression system.

Conclusion

Our findings suggested that C. sinensis activates CsRBOH and ROS-related genes, leading to ROS accumulation to resist the invasion by D. citri. This study laid the foundation for future research on molecular mechanisms and breeding of C. sinensis cultivars resistant to citrus melanose.
Antibiotics with antibiofilm activity – rifampicin and beyond
Authors: Ferreira Luís , Pos Ema , Nogueira Daniela Rodrigues , Ferreira Filipa Pinto , Sousa Ricardo , Abreu Miguel Araújo
Published: August 2024

The management of prosthetic joint infections is a complex and multilayered process that is additionally complicated by the formation of bacterial biofilm. Foreign material provides the ideal grounds for the development of an intricate matrix that hinders treatment and creates a difficult environment for antibiotics to act. Surgical intervention is often warranted but requires appropriate adjunctive therapy. Despite available guidelines, several aspects of antibiotic therapy with antibiofilm activity lack clear definition. Given the escalating challenges posed by antimicrobial resistance, extended treatment durations, and tolerance issues, it is essential to ensure that antimicrobials with antibiofilm activity are both potent and diverse. Evidence of biofilm-active drugs is highlighted, and alternatives to classical regimens are further discussed.
Low electric current in a bioelectrochemical system facilitates ethanol production from CO using CO-enriched mixed culture
Authors: Im Chaeho , Kim Minsoo , Kim Jung Rae , Valgepea Kaspar , Modin Oskar , Nygård Yvonne , Franzén Carl Johan
Published: August 2024

Fossil resources must be replaced by renewable resources in production systems to mitigate green-house gas emissions and combat climate change. Electro-fermentation utilizes a bioelectrochemical system (BES) to valorize industrial and municipal waste. Current electro-fermentation research is mainly focused on microbial electrosynthesis using CO2 for producing commodity chemicals and replacing petroleum-based infrastructures. However, slow production rates and low titers of metabolites during CO2-based microbial electrosynthesis impede its implementation to the real application in the near future. On the other hand, CO is a highly reactive gas and an abundant feedstock discharged from fossil fuel-based industry. Here, we investigated CO and CO2 electro-fermentation, using a CO-enriched culture. Fresh cow fecal waste was enriched under an atmosphere of 50% CO and 20% CO2 in N2 using serial cultivation. The CO-enriched culture was dominated by Clostridium autoethanogenum (≥89%) and showed electro-activity in a BES reactor with CO2 sparging. When 50% CO was included in the 20% CO2 gas with 10 mA applied current, acetate and ethanol were produced up to 12.9 ± 2.7 mM and 2.7 ± 1.1 mM, respectively. The coulombic efficiency was estimated to 148% ± 8% without an electron mediator. At 25 mA, the culture showed faster initial growth and acetate production but no ethanol production, and only at 86% ± 4% coulombic efficiency. The maximum optical density (OD) of 10 mA and 25 mA reactors were 0.29 ± 0.07 and 0.41 ± 0.03, respectively, whereas it was 0.77 ± 0.19 without electric current. These results show that CO electro-fermentation at low current can be an alternative way of valorizing industrial waste gas using a bioelectrochemical system.
Genes associated with fitness and disease severity in the pan-genome of mastitis-associated Escherichia coli
Authors: Olson Michael A. , Cullimore Caz , Hutchison Weston D. , Grimsrud Aleksander , Nobrega Diego , De Buck Jeroen , Barkema Herman W. , Wilson Eric , Pickett Brett E. , Erickson David L.
Published: August 2024

Introduction

Bovine mastitis caused by Escherichia coli compromises animal health and inflicts substantial product losses in dairy farming. It may manifest as subclinical through severe acute disease and can be transient or persistent in nature. Little is known about bacterial factors that impact clinical outcomes or allow some strains to outcompete others in the mammary gland (MG) environment. Mastitis-associated E. coli (MAEC) may have distinctive characteristics which may contribute to the varied nature of the disease. Given their high levels of intraspecies genetic variability, virulence factors of commonly used MAEC model strains may not be relevant to all members of this group.

Methods

In this study, we sequenced the genomes of 96 MAEC strains isolated from cattle with clinical mastitis (CM). We utilized clinical severity data to perform genome-wide association studies to identify accessory genes associated with strains isolated from mild or severe CM, or with high or low competitive fitness during in vivo competition assays. Genes associated with mastitis pathogens or commensal strains isolated from bovine sources were also identified.

Results

A type-2 secretion system (T2SS) and a chitinase (ChiA) exported by this system were strongly associated with pathogenic isolates compared with commensal strains. Deletion of chiA from MAEC isolates decreased their adherence to cultured bovine mammary epithelial cells.

Discussion

The increased fitness associated with strains possessing this gene may be due to better attachment in the MG. Overall, these results provide a much richer understanding of MAEC and suggest bacterial processes that may underlie the clinical diversity associated with mastitis and their adaptation to this unique environment.