bluuebunny/crossref_metadata_2025 huggingface dataset:
[Retracted] Comparative Analysis of Machine Learning Methods for Breast Cancer Classification in Genetic Sequences
Authors: Kurian Babymol , Jyothi V.L
Published: September 2022

Breast cancer is the leading cancer in women, which accounts for millions of deaths worldwide. Early and accurate detection, prognosis, cure, and prevention of breast cancer is a major challenge to society. Hence, a precise and reliable system is vital for the classification of cancerous sequences. Machine learning classifiers contribute much to the process of early prediction and diagnosis of cancer. In this paper, a comparative study of four machine learning classifiers such as random forest, decision tree, AdaBoost, and gradient boosting is implemented for the classification of a benign and malignant tumor. To derive the most efficient machine learning model, NCBI datasets are utilized. Performance evaluation is conducted, and all four classifiers are compared based on the results. The aim of the work is to derive the most efficient machine‐learning model for the diagnosis of breast cancer. It was observed that gradient boosting outperformed all other models and achieved a classification accuracy of 95.82%.
[Retracted] Analysis of Heidegger’s “Ge‐Stell” Thought of Modern Technology and Art
Authors: Li Jialin , Zhang Bin
Published: September 2022

Heidegger is not actually an antitechnologist or a revivalist. He does not think we need to escape from technology while criticizing it, nor does he miss a certain “golden age” in human history. Heidegger cannot provide us with specific methods to solve many problems in the technological age, but his reflection and questioning provide us with a possible way of redemption, which is of great significance to the development of our current era. After analyzing Heidegger’s related works and related literature by many scholars, this paper finds that most of the research stays on aspects such as the existence, the nature of art, the nature of technology, the crisis brought about by technology, and the rescue of technology by art. Part of it involves the relationship between technology and art, but rarely concentrates on thinking about the relationship between technology and art. Based on this, through the exploration and analysis of the origin of ancient techniques and the reconsideration of the essence of modern technology, this paper takes the “Ge‐stell” thought in the context of Heidegger’s thinking on technology as the breakthrough point and reexamines technology. It understands and expounds the development of art; tries to study the inner connection and connotation between Heidegger’s modern technology, art, and modern technology “Ge‐stell”; and grasps the relationship between technology and art as a whole. By analyzing and pointing out the “Ge‐stell” essence of technology, the blood relationship between technology and art has been cut off, and art has been brought into the control of technology, resulting in an unprecedented survival crisis for human beings. Finally, the rescue in the technological era is proposed. It can provide philosophical guidance and new thinking for the development of the current society and the plight of the times it is facing.
The Impact of Improved Oral Care Methods on the Oral Health of Patients Undergoing Transoral Mechanical Ventilation
Authors: Shen Yijun , Dai Ling , Zhu Yanwen , Lang Yishu
Published: September 2022

Objective. To explore the effects of improved oral care on the number of oropharyngeal bacteria and the incidence of ventilator-associated pneumonia in patients undergoing mechanical ventilation through oral endotracheal intubation by improving conventional oral care methods and operating procedures and to evaluate the quality of improved oral care and effect. Methods. A total of 100 cases of mechanically ventilated patients with oral endotracheal intubation who met the inclusion criteria were randomly divided into the observation group and control group with 50 cases each. The control group took routine oral care, that is, scrubbing 3 times per day, and the oral care solution was selected as physiological brine. The observation group improved the conventional oral care method, namely, oral scrubbing before intubation, brushing and washing after intubation, 3 times per day, and 0.1% povidone-iodine in oral care solution. Analysis and comparison of the oral bacterial flora, oral cleanliness, and incidence of ventilator-associated pneumonia, mechanical ventilation time, ICU hospitalization time, and mortality rate of the two groups of patients were analyzed and compared. The relevant data were collected and processed for statistical processing. Results. The oral bacterial flora of the two groups of patients before oral care after mechanical ventilation after oral tracheal intubation was compared, and there was no significant statistical difference (

P
>
0.05

). After nursing, the oral bacterial flora of the observation group at 8 h, 16 h, and 24 h after intubation was significantly lower than that of the control group. Statistics showed that the difference was statistically significant (

P
<
0.05

). After nursing, the number of patients with oral cleanliness in the observation group was significantly higher than that of the control group, while the incidence of ventilator-associated pneumonia in the observation group was 8% significantly lower than that of the control group 14%. Statistics show that this difference is statistically significant (

P
<
0.05

). After nursing, the observation group’s oral cleanliness score, mechanical ventilation time, ICU hospitalization time, and GCS score were better than those of the control group. Statistics showed that the difference was statistically significant (

P
<
0.05

). The mortality of the observation group was significantly lower than that of the control group, which was not statistically significant (

P
>
0.05

). Conclusion. Oral care can effectively reduce the number of oropharyngeal bacteria in patients who are mechanically ventilated through orotracheal intubation and significantly reduce the incidence of ventilator-associated pneumonia.
Prediction of Higher Education Cost and Analysis of Sharing Ability Based on Artificial Neural Network
Authors: Xia Zilong , Yue Xin , Niu FanChao , Hu Zhihua
Published: September 2022

In order to explore how to realize the cost prediction and sharing ability of higher education, this paper proposes an analysis of the cost prediction and sharing ability of higher education based on artificial neural network. This method explores how to realize the cost prediction of higher education through the key technical problems and solutions of information recommendation based on artificial neural network. The research shows that the ability of college education cost prediction and sharing based on artificial neural network is 61% higher than that of traditional cost prediction and sharing. With the help of BP neural network algorithm, the accuracy of cost prediction can be maintained above 90%. It is proved that the artificial neural network algorithm can effectively improve the cost forecasting, financial system, and cost management system of colleges and universities.
Construction of Molecular Subtype and Prognosis Prediction Model of Osteosarcoma Based on Aging-Related Genes
Authors: Dong Chunli , Sun Yindi , Zhang Ying , Qin Bianni , Lei Tao
Published: September 2022

Background. Osteosarcoma (OS) is a rare form of malignant bone cancer that is usually detected in young adults and adolescents. This disease shows a poor prognosis owing to its metastatic status and resistance to chemotherapy. Hence, it is necessary to design a risk model that can successfully forecast the OS prognosis in patients. Methods. The researchers retrieved the RNA sequencing data and follow-up clinical data related to OS patients from the TARGET and GEO databases, respectively. The coxph function in R software was used for carrying out the Univariate Cox regression analysis for deriving the aging-based genes related sto the OS prognosis. The researchers conducted consistency clustering using the ConcensusClusterPlus R package. The R software package ESTIMATE, MCPcounter, and GSVA packages were used for assessing the immune scores of various subtypes using the ssGSEA technique, respectively. The Univariate Cox and Lasso regression analyses were used for screening and developing a risk model. The ROC curves were constructed, using the pROC package. The performance of their developed risk model and designed survival curve was conducted, with the help of the Survminer package. Results. The OS patients were classified into 2 categories, as per the aging-related genes. The results revealed that the Cluster 1 patients showed a better prognosis than the Cluster 2 patients. Both clusters showed different immune microenvironments. Additional screening of the prognosis-associated genes revealed the presence of 5 genes, i.e., ERCC4, GPX4, EPS8, TERT, and STAT5A, and these data were used for developing the risk model. This risk model categorized the training set samples into the high- and low-risk groups. The patients classified into the high-risk group showed a poor OS prognosis compared to the low-risk patients. The researchers verified the reliability and robustness of the designed 5-gene signature using the internal and external datasets. This risk model was able to effectively predict the prognosis even in the samples having differing clinical features. Compared with other models, the 5- gene model performs better in predicting the risk of osteosarcoma. Conclusion. The 5-gene signature developed by the researchers in this study could be effectively used for forecasting the OS prognosis in patients.
Efficient Personalized Recommendation Based on Federated Learning with Similarity Ciphertext Calculation
Authors: Wang Xixian , Wang Xiaoming , Huang Binrui , Dai Mingzhan , Li Jianwei
Published: September 2022

With the popularity of big data, people get less useful information because of the large amount of data, which makes the Recommender System come into being. However, the privacy and accuracy of the Recommender System still have great challenges. To address these challenges, an efficient personalized recommendation scheme is proposed based on Federated Learning with similarity ciphertext calculation. In this paper, we first design a Similarity calculation algorithm based on Orthogonal Matrix in Ciphertext (SOMC), which can compute the Similarity between users’ demand and Items’ attributes under ciphertext with a low calculation cost. Based on SOMC, we construct an efficient recommendation scheme by employing the Federated Learning framework. The important feature of the proposed approach is improving the accuracy of recommendation while ensuring the privacy of both the users and the Agents. Furthermore, the Agents with good performance are selected according to their Reliability scores to participate in the federal recommendation, so as to further make the accuracy of recommendation better. Under the defined threat model, it is proved that the proposed scheme can meet the privacy requirements of users and Agents. Experiments show that the proposed scheme has optimized accuracy and efficiency compared with existing schemes.
Artificial Intelligence-Powered Contactless Face Recognition Technique for Internet of Things Access for Smart Mobility
Authors: Hiremani Nirmala , Hasan Mohammad Kamrul , Basavaraju T. G. , Islam Shayla , Alboaneen Dabiah , Alkayal Entisar , Alharbi Nesreen M. , Mansor Zulkefli , Amanlou Sanaz
Published: September 2022

A contactless system became necessary for smart mobility during the COVID-19 pandemic. There are many touchpoints in private and public areas where contact is essential, such as intelligent transportation systems for vaccine carriers, patient ambulances, elevators, metros, buses, hospitals, and banks. A secured contactless device reduces the chances of COVID-19 infection spread. Several devices use smart cards, fingerprint identification, or code-based access. Most of these devices require some form of touch. The cost of such devices varies, depending on their capability and intended use. Sensors developed by using artificial intelligence (AI) to provide secured access are an emerging area. This paper presents an AI-powered contactless face recognition system. The solution has the Internet of Things (IoT) enabled access system. To identify a person, it uses AI assistance for face recognition with the help of Python Dlib’s facial recognition network. Dlib offers a wide range of functionality across several machine learning sectors and is open-source. The Arduino Uno (ATmega328P) and STK500 protocol has been used for communication to testify and validate the performance of the proposed technique. The objective is to detect and recognize faces by the proposed contactless approach. The obtained result shows 92% accuracy, 94% sensitivity, 96% precision and FRR 6% for face detection. There is a significant improvement in FRR in our work compared to the published 27.27%. The implemented solution in this paper provides accurate and secure contactless access to conventional, readily available techniques in public health safety.
Construction of Safety Early Warning Model for Construction of Engineering Based on Convolution Neural Network
Authors: Zhao Changge
Published: September 2022

In recent years, China’s engineering construction management level has been greatly improved, but compared with other industries, the construction industry still has low production efficiency, serious waste, and low level of information problems, and especially in the process of engineering management practice, schedule delay has become the focus of engineering management problems. With the continuous development of science and technology, computer and information technology have been continuously applied in engineering, among which deep neural network (DNN) technology, lean management, information visualization technology, and other technologies have become the hot spot of industry research, and the application of these emerging technologies to improve the level of project schedule control has become an urgent demand of the industry. Therefore, on the basis of deep learning, this paper analyzes the principle and application of object detection and feature extraction constructed by neural network and combines text feature extraction and image feature extraction methods. This application provides a new idea for the development of the construction industry.
E-Commerce Intelligent Logistics Data Based on Neural Network Model
Authors: Mu Wei , Ding HePing
Published: September 2022

Not only e-commerce is developing rapidly, but also intelligent logistics technology is becoming more and more mature. In daily life, we can track the logistics information synchronously. On the smartphone app, the logistics information can be viewed at any time. However, the current processing algorithms are not enough for the exponentially increasing data volume and increasingly complex data types. This paper aims to analyze the massive data generated by e-commerce intelligent logistics. In this paper, a new classification algorithm is proposed, which is improved on the ordinary ladder classification algorithm, and artificial neural networks are added for automatic iterative update learning, which can automatically classify a large amount of data. The experimental results show that the classification error rate of the improved algorithm is less than 5%, and when the sample size is less than 30,000, the improved algorithm can significantly outperform the original algorithm.
Genetic Diversity, Carbapenem Resistance Genes, and Biofilm Formation in UPEC Isolated from Patients with Catheter-Associated Urinary Tract Infection in North of Iran
Authors: Nasrollahian Sina , Halaji Mehrdad , Hosseini Akramasadat , Teimourian Mohammad , Armaki Mojtaba Taghizadeh , Rajabnia Mehdi , Gholinia Hemmat , Pournajaf Abazar
Published: September 2022

Background. Infections due to carbapenem-resistant Enterobacteriaceae (CRE) are associated in patients with urinary catheters alarming rate of emergency status. The aim of this study is to investigate the molecular causes of carbapenem resistance among UPEC as well as antimicrobial resistance trends. Additionally, the potential of isolates to produce biofilms, in addition to their clonal and genetic diversity, was investigated. Material and Methods. A cross-sectional study was accomplished on a collection of 76 non-duplicate UPEC isolates obtained from CAUTIs from May 2021 to September 2021. The modified carbapenem inactivation method (mCIM) and EDTA-modified carbapenem inactivation method (eCIM) test was performed for the detection of carbapenemase and metallo-beta-lactamase activity. Also, the presence of carbapenemase genes was determined using PCR assays. In 96-well microtiter plates, biofilm development was evaluated. ERIC-PCR was used to investigate the clonal and genetic variety of isolates. Results. A total of 76 confirmed UPEC isolates were obtained from patients mentioned to teaching hospitals in Babol, Iran. The results of antibiotic susceptibility testing revealed a high rate of antibiotic resistance against nalidixic acid (81.6%) and trimethoprim-sulfamethoxazole (80.3%). Among UPEC isolates, 63.2% and 13.2% of UPEC isolates were positive for MBL production. The frequencies of the studied genes are in order of blaNDM (14.5%), blaOXA-23 (2.6%), and blaOXA-48 (2.6%). Forty-two isolates (55.3%) were positive for biofilm formation. ERIC-PCR revealed that UPEC isolates could be categorized into nine clusters A-I and five isolates were categorized as a singleton. Conclusion. The high prevalence of MDR and carbapenemase-producing isolates among the UPEC strain in this investigation is concerning. Moreover, the blaNDM was the most frequent cause of producing metallo-beta-lactamase and carbapenemase. Also, analysis revealed a partial genetic similarity among the studied isolates, indicating that the same UPEC clones may have spread to other hospital units.
Analysis of Pathogenic Vibrio Contamination in Marine Products along China Based on Fluorescence Quantitative PCR
Authors: Wang Tong , Wan Shuo , Huang Jian-Lian , Sui Zhi-Hai , Gao Cui-Juan , Liu Yun-Guo
Published: September 2022

At present, aquatic product pollution has become the main root of frequent food safety problems and causes economic losses. Vibrio is one of the main pathogens causing foodborne diseases. In this study, in order to uncover the pollution status of pathogenic Vibrio in the marine products of China, a total of 646 aquatic products were collected and analyzed from 10 coastal cities in China. Five kinds of pathogenic Vibrio were separated from these samples and monitored to explore the relationship between pollution and the pathogen. Real-time fluorescence quantitative PCR was adopted to detect foodborne Vibrio quantitatively in marine aquatic products. Aquatic pathogenic Vibrio was collected in different regions, different types of aquatic products, and different sampling places, and the difference in detection rate was statistically significant through statistical analysis. This study made a frame for the pollution degree of pathogenic Vibrio in marine products in China and established the dominant flora of pathogenic Vibrio in different types of aquatic products, which provides a theoretical basis for food safety supervision departments to take targeted prevention and control measures.
A Probody T Cell–Engaging Bispecific Antibody Targeting EGFR and CD3 Inhibits Colon Cancer Growth with Limited Toxicity
Authors: Boustany Leila M. , LaPorte Sherry L. , Wong Laurie , White Clayton , Vinod Veena , Shen Joel , Yu Wendy , Koditek David , Winter Michael B. , Moore Stephen J. , Mei Li , Diep Linnea , Huang Yuanhui , Liu Shouchun , Vasiljeva Olga , West Jim , Richardson Jennifer , Irving Bryan , Belvin Marcia , Kavanaugh W. Michael
Published: September 2022

T cell–engaging bispecific antibodies (TCB) are highly potent therapeutics that can recruit and activate cytotoxic T cells to stimulate an antitumor immune response. However, the development of TCBs against solid tumors has been limited by significant on-target toxicity to normal tissues. Probody therapeutics have been developed as a novel class of recombinant, protease-activated antibody prodrugs that are “masked” to reduce antigen binding in healthy tissues but can become conditionally unmasked by proteases that are preferentially active in the tumor microenvironment (TME). Here, we describe the preclinical efficacy and safety of CI107, a Probody TCB targeting EGFR and CD3. In vitro, the protease-activated, unmasked CI107 effectively bound EGFR and CD3 expressed on the surface of cells and induced T-cell activation, cytokine release, and cytotoxicity toward tumor cells. In contrast, dually masked CI107 displayed a >500-fold reduction in antigen binding and >15,000-fold reduction in cytotoxic activity. In vivo, CI107 potently induced dose-dependent tumor regression of established colon cancer xenografts in mice engrafted with human peripheral blood mononuclear cells. Furthermore, the MTD of CI107 in cynomolgus monkeys was more than 60-fold higher than that of the unmasked TCB, and much lower levels of toxicity were observed in animals receiving CI107. Therefore, by localizing activity to the TME and thus limiting toxicity to normal tissues, this Probody TCB demonstrates the potential to expand clinical opportunities for TCBs as effective anticancer therapies for solid tumor indications.

Significance:

A conditionally active EGFR-CD3 T cell–engaging Probody therapeutic expands the safety window of bispecific antibodies while maintaining efficacy in preclinical solid tumor settings.
Postoperative Plasmacytoid Dendritic Cells Secrete IFNα to Promote Recruitment of Myeloid-Derived Suppressor Cells and Drive Hepatocellular Carcinoma Recurrence
Authors: Pang Li , Yeung Oscar W.H. , Ng Kevin T.P. , Liu Hui , Zhu Jiye , Liu Jiang , Yang Xinxiang , Ding Tao , Qiu Wenqi , Wang Yuewen , Chiu T.L. Shirley , Chen Zhiwei , Lo Chung-Mau , Man Kwan
Published: September 2022

Patients with hepatocellular carcinoma (HCC) confront a high incidence of tumor recurrence after curative surgical resection. Hepatic ischemia-reperfusion injury (IRI) is the major consequence of surgical stress during hepatectomy. Although it has been suggested that hepatic IRI-induced immunosuppression could contribute to tumor relapse after surgery, the underlying mechanisms have not been fully defined. Here, using a multiplex cytokine array, we found that levels of postoperative IFNα serve as an independent risk factor for tumor recurrence in 100 patients with HCC with curative hepatectomy. Plasmacytoid dendritic cells (pDC), the major source of IFNα, were activated after surgery and correlated with poor disease-free survival. Functionally, IFNα was responsible for mobilization of myeloid-derived suppressor cells (MDSC) following hepatic IRI. Conditioned medium from IFNα-treated hepatocytes mediated the migration of MDSCs in vitro. Mechanistically, IFNα upregulated IRF1 to promote hepatocyte expression of CX3CL1, which subsequently recruited CX3CR1+ monocytic MDSCs. Knockdown of Irf1 or Cx3cl1 in hepatocytes significantly inhibited the accumulation of monocytic MDSCs in vivo. Therapeutically, elimination of pDCs, IFNα, or CX3CR1 could restore the tumor-killing activity of CD8+ T cells, hence limiting tumor growth and lung metastasis following hepatic IRI. Taken together, these data suggest that IFNα-producing pDCs drive CX3CR1+ MDSC recruitment via hepatocyte IRF1/CX3CL1 signaling and lead to tumor recurrence after hepatectomy in HCC. Targeting pDCs and the IFNα/CX3CL1/CX3CR1 axis could inhibit surgical stress–induced HCC recurrence by attenuating postoperative immunosuppression.

Significance:

IFNα secreted by plasmacytoid dendritic cells drives postoperative immunosuppression and early recurrence of hepatocellular carcinoma, providing new biomarkers and therapeutic targets to improve patient outcomes after surgical resection.
Multi-omic Characterization of Pancreatic Ductal Adenocarcinoma RelatesCXCR4mRNA Expression Levels to Potential Clinical Targets
Authors: Kocher Florian , Puccini Alberto , Untergasser Gerold , Martowicz Agnieszka , Zimmer Kai , Pircher Andreas , Baca Yasmine , Xiu Joanne , Haybaeck Johannes , Tymoszuk Piotr , Goldberg Richard M. , Petrillo Angelica , Shields Anthony F. , Salem Mohamed E. , Marshall John L. , Hall Michael , Korn W. Michael , Nabhan Chadi , Battaglin Francesca , Lenz Heinz-Josef , Lou Emil , Choo Su-Pin , Toh Chee-Keong , Gasteiger Silvia , Pichler Renate , Wolf Dominik , Seeber Andreas
Published: September 2022

Purpose:

Chemokines are essential for immune cell trafficking and are considered to have a major impact on the composition of the tumor microenvironment. CX-chemokine receptor 4 (CXCR4) is associated with poor differentiation, metastasis, and prognosis in pancreatic ductal adenocarcinoma (PDAC). This study provides a comprehensive molecular portrait of PDAC according to CXCR4 mRNA expression levels.

Experimental Design:

The Cancer Genome Atlas database was used to explore molecular and immunologic features associated with CXCR4 mRNA expression in PDAC. A large real-word dataset (n = 3,647) served for validation and further exploratory analyses. Single-cell RNA analyses on a publicly available dataset and in-house multiplex immunofluorescence (mIF) experiments were performed to elaborate cellular localization of CXCR4.

Results:

High CXCR4 mRNA expression (CXCR4high) was associated with increased infiltration of regulatory T cells, CD8+ T cells, and macrophages, and upregulation of several immune-related genes, including immune checkpoint transcripts (e.g., TIGIT, CD274, PDCD1). Analysis of the validation cohort confirmed the CXCR4-dependent immunologic TME composition in PDAC irrespective of microsatellite instability–high/mismatch repair–deficient or tumor mutational burden. Single-cell RNA analysis and mIF revealed that CXCR4 was mainly expressed by macrophages and T-cell subsets. Clinical relevance of our finding is supported by an improved survival of CXCR4high PDAC.

Conclusions:

High intratumoral CXCR4 mRNA expression is linked to a T cell– and macrophage-rich PDAC phenotype with high expression of inhibitory immune checkpoints. Thus, our findings might serve as a rationale to investigate CXCR4 as a predictive biomarker in patients with PDAC undergoing immune checkpoint inhibition.
Subtype and Site Specific–Induced Metabolic Vulnerabilities in Prostate Cancer
Authors: Mossa Federica , Robesti Daniele , Sumankalai Ramachandran , Corey Eva , Titus Mark , Kang Yuqi , Zhang Jianhua , Briganti Alberto , Montorsi Francesco , Vellano Christopher P. , Marszalek Joseph R. , Frigo Daniel E. , Logothetis Christopher J. , Gujral Taranjit S. , Dondossola Eleonora
Published: September 2022

Aberrant metabolic functions play a crucial role in prostate cancer progression and lethality. Currently, limited knowledge is available on subtype-specific metabolic features and their implications for treatment. We therefore investigated the metabolic determinants of the two major subtypes of castration-resistant prostate cancer [androgen receptor–expressing prostate cancer (ARPC) and aggressive variant prostate cancer (AVPC)]. Transcriptomic analyses revealed enrichment of gene sets involved in oxidative phosphorylation (OXPHOS) in ARPC tumor samples compared with AVPC. Unbiased screening of metabolic signaling pathways in patient-derived xenograft models by proteomic analyses further supported an enrichment of OXPHOS in ARPC compared with AVPC, and a skewing toward glycolysis by AVPC. In vitro, ARPC C4–2B cells depended on aerobic respiration, while AVPC PC3 cells relied more heavily on glycolysis, as further confirmed by pharmacologic interference using IACS-10759, a clinical-grade inhibitor of OXPHOS. In vivo studies confirmed IACS-10759′s inhibitory effects in subcutaneous and bone-localized C4–2B tumors, and no effect in subcutaneous PC3 tumors. Unexpectedly, IACS-10759 inhibited PC3 tumor growth in bone, indicating microenvironment-induced metabolic reprogramming. These results suggest that castration-resistant ARPC and AVPC exhibit different metabolic dependencies, which can further undergo metabolic reprogramming in bone.

Implications:

These vulnerabilities may be exploited with mechanistically novel treatments, such as those targeting OXPHOS alone or possibly in combination with existing therapies. In addition, our findings underscore the impact of the tumor microenvironment in reprogramming prostate cancer metabolism.
Cathelicidins Induce Toll-Interacting Protein Synthesis to Prevent Apoptosis in Colonic Epithelium
Authors: Holani Ravi , Rathnayaka Chathurika , Blyth Graham A.D. , Babbar Anshu , Lahiri Priyoshi , Young Daniel , Dufour Antoine , Hollenberg Morley D. , McKay Derek M. , Cobo Eduardo R.
Published: September 2022

Cathelicidin peptides secreted by leukocytes and epithelial cells are microbicidal but also regulate pathogen sensing via toll-like receptors (TLRs) in the colon by mechanisms that are not fully understood. Herein, analyses with the attaching/effacing pathogen Citrobacter rodentium model of colitis in cathelicidin-deficient (Camp−/−) mice, and colonic epithelia demonstrate that cathelicidins prevent apoptosis by sustaining post-transcriptional synthesis of a TLR adapter, toll-interacting protein (TOLLIP). Cathelicidins induced phosphorylation-activation of epidermal growth factor receptor (EGFR)-kinase, which phosphorylated-inactivated miRNA-activating enzyme Argonaute 2 (AGO2), thus reducing availability of the TOLLIP repressor miRNA-31. Cathelicidins promoted stability of TOLLIP protein via a proteosome-dependent pathway. This cathelicidin-induced TOLLIP upregulation prevented apoptosis in the colonic epithelium by reducing levels of caspase-3 and poly (ADP-ribose) polymerase (PARP)-1 in response to the proinflammatory cytokines, interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα). Further, Camp−/− colonic epithelial cells were more susceptible to apoptosis during C. rodentium infection than wild-type cells. This antiapoptotic effect of cathelicidins, maintaining epithelial TOLLIP protein in the gut, provides insight into cathelicidin’s ability to regulate TLR signaling and prevent exacerbated inflammation.
Audio Feature Analysis for Acoustic Pain Detection in Term Newborns
Authors: Giordano Vito , Luister Alexandra , Reuter Christoph , Czedik-Eysenberg Isabella , Singer Dominique , Steyrl David , Vettorazzi Eik , Deindl Philipp
Published: September 2022

Introduction: Crying newborns signal a need or discomfort as part of the innate communication system. Exposure to pain is related to infants’ unfavorable neurodevelopmental outcomes. There is a tremendous need for more objective methods to assess neonatal pain. An audio analysis of acoustic utterances could provide specific information on the patient’s pain level. Methods: We analyzed 67 videos of 33 term-born newborns recorded during a planned capillary blood sample, including the stimuli, non-noxious thermal stimulus, short noxious stimulus, and prolonged unpleasant stimulus, between December 2020 and March 2021. Two expert raters evaluated the infants’ pain responses using the Neonatal Facial Coding System (NFCS). The mean values of 123 timbre features of the recorded audio data were analyzed by using specific toolboxes and libraries from the following programming environments: MIRtoolbox (MATLAB), MiningSuite (MATLAB), Essentia (Python), AudioCommons timbral models (Python), and Librosa (Python). Results: The NFCS values were significantly higher during the short noxious stimulus (p < 0.001) and prolonged unpleasant stimulus (p < 0.001) than during the non-noxious thermal stimulus, whereas NFCS values during the short noxious stimulus and prolonged unpleasant stimulus were similar (p = 0.79). Brightness, roughness, percussive energy, and attack times were identified as the features having the highest impact on the NFCS. Conclusion: This hypothesis-generating study identified several salient acoustic features highly associated with pain responses in term newborns. Our analysis is an encouraging starting point for the targeted analysis of pain-specific acoustic features of neonatal cries and vocalizations from the perspective of real-time acoustic processing.
Impact of Potentially Inappropriate Medications on Kidney Function in Chronic Kidney Disease: Retrospective Cohort Study
Authors: Kimura Hiroshi , Yoshida Satomi , Takeuchi Masato , Kawakami Koji
Published: September 2022

Introduction: Chronic kidney disease (CKD) represents a major public health burden. Potential inappropriate medications (PIMs) are common in patients with CKD. However, its impact on kidney outcomes has not been adequately elucidated for middle-aged patients. This study aimed to clarify the prescription status of PIMs for middle-aged patients with CKD and its effect on kidney function decline. Methods: Using an administrative claims database in Japan, a retrospective cohort study was conducted among Japanese patients with CKD (aged 20–74) who underwent annual health check-ups at least three times between April 2008 and December 2020. PIM exposure was defined as medications to be avoided in older adults as defined by the 2019 American Geriatrics Society Beers Criteria. The association between the number of prescribed PIMs and the decline in estimated glomerular filtration rate (eGFR) was examined using logistic regression models adjusted for clinical characteristics and laboratory variables. Results: A total of 43,143 patients with CKD (mean age 57 years, median eGFR: 52 mL/min/1.73 m2) were analyzed, and approximately 40% of the patients were prescribed one or more PIMs. The most commonly prescribed PIMs were pain medications (18.5%), followed by gastrointestinal medications (9.8%), central nervous system medications (8.6%), and cardiovascular medications (8.6%). After adjustment, exposure to 2 or ≥3 PIMs was associated with an increased risk of 30% eGFR decline (adjusted odds ratio 1.71 [95% confidence interval, 1.24–2.37] and 1.65 [95% confidence interval, 1.08–2.52], respectively) as compared to the control group. Conclusion: This study showed that middle-aged patients with CKD who were prescribed ≥2 PIM had an increased risk of progression of CKD. Further studies are needed to analyze whether deprescribing steps contribute to reduce PIM prescriptions and prevent CKD progression.
Principles for Evidence-Based and Sustainable Food System Innovations for Healthier Diets
Authors: Ferraboschi Chiara , Monroy-Gomez Jimena , Gavin-Smith Breda , Beesabathuni Kalpana , Tshering Puja , Lingala Srujith , Bainsla Neha , Amanquah Daniel , Kumari Priyanka , Gabrielle van Zutphen Kesso , Kraemer Klaus
Published: September 2022

Climate change, rapid urbanization, war, and economic recession are key drivers of the current food systems’ disruption, which has been exacerbated by the COVID pandemic. Local, regional, and global food systems are unable to provide consumers with nutritious and affordable diets. Suboptimal diets exacerbate the triple burden of malnutrition, with micronutrient deficiencies affecting more than two billion people, two billion people suffering from overweight, and more than 140 million children who are stunted. The unaffordability of nutritious diets represents an obstacle for many, especially in low- and middle-income countries where healthy diets are five times more expensive than starchy staple diets. Food system transformations are urgently required to provide consumers with more affordable and nutritious diets that are capable of meeting social and environmental challenges. In this review, we underline the critical role of innovation within the food system transformation discourse. We aim to define principles for implementing evidence-based and long-term food system innovations that are economically, socially, and environmentally sustain­able and, above all, aimed at improving diets and public health. We begin by defining and describing the role of innovation in the transformation of food systems and uncover the major barriers to implementing these innovations. Lastly, we explore case studies that demonstrate successful innovations for healthier diets.
Co-Occurrence of Hypohidrotic Ectodermal Dysplasia and Food Protein-Induced Enterocolitis Syndrome: A Report of a New Ectodysplasin A Variant
Authors: Salik Déborah , Moulart Florine , Marangoni Martina , Salamouras Dimitrios , André Marie-Sophie , Vilain Catheline
Published: September 2022

Introduction: Ectodermal dysplasias (EDs) are a large group of rare and complex genetic disorders, affecting the development of two or more ectodermal structures. Hypohidrotic ED (HED) is the most frequent ED’s phenotype and is characterized by hypodontia, hypotrichosis, and hypo/anhidrosis, leading to heat intolerance and hyperthermia. Case Presentation: We report a case of a 2-year-old girl with hair and teeth abnormalities associated with severe digestive symptoms responsible for failure to thrive. Genetic analysis by mass sequencing in parallel on a 4,867-gene panel was performed in duo (index case and her mother). The girl showed the presence of a new de novo c.100dupG variant in EDA responsible for HED associated with a diagnosis of food protein-induced enterocolitis syndrome (FPIES). Conclusion: We describe a patient with HED and a new EDA variant associated with a diagnosis of FPIES, both implicating increased intestinal permeability. The inclusion of FPIES as a possible digestive symptom of HED can be suggested, although it may occur only in a context of atopy.
Astrocyte Progenitors Derived From Patients With Alzheimer Disease Do Not Impair Stroke Recovery in Mice
Authors: Välimäki Nelli-Noora , Bakreen Abdulhameed , Häkli Sara , Dhungana Hiramani , Keuters Meike H. , Dunlop Yannick , Koskuvi Marja , Keksa-Goldsteine Velta , Oksanen Minna , Jäntti Henna , Lehtonen Šárka , Malm Tarja , Koistinaho Jari , Jolkkonen Jukka
Published: September 2022

Background:

Species-specific differences in astrocytes and their Alzheimer disease-associated pathology may influence cellular responses to other insults. Herein, human glial chimeric mice were generated to evaluate how Alzheimer disease predisposing genetic background in human astrocytes contributes to behavioral outcome and brain pathology after cortical photothrombotic ischemia.

Methods:

Neonatal (P0) immunodeficient mice of both sexes were transplanted with induced pluripotent stem cell–derived astrocyte progenitors from Alzheimer disease patients carrying
PSEN1
exon 9 deletion (PSEN1 ΔE9), with isogenic controls, with cells from a healthy donor, or with mouse astrocytes or vehicle. After 14 months, a photothrombotic lesion was produced with Rose Bengal in the motor cortex. Behavior was assessed before ischemia and 1 and 4 weeks after the induction of stroke, followed by tissue perfusion for histology.

Results:

Open field, cylinder, and grid-walking tests showed a persistent locomotor and sensorimotor impairment after ischemia and female mice had larger infarct sizes; yet, these were not affected by astrocytes with PSEN1 ΔE9 background. Staining for human nuclear antigen confirmed that human cells successfully engrafted throughout the mouse brain. However, only a small number of human cells were positive for astrocytic marker GFAP (glial fibrillary acidic protein), mostly located in the corpus callosum and retaining complex human-specific morphology with longer processes compared with host counterparts. While host astrocytes formed the glial scar, human astrocytes were scattered in small numbers close to the lesion boundary. Aβ (beta-amyloid) deposits were not present in PSEN1 ΔE9 astrocyte-transplanted mice.

Conclusions:

Transplanted human cells survived and distributed widely in the host brain but had no impact on severity of ischemic damage after cortical photothrombosis in chimeric mice. Only a small number of transplanted human astrocytes acquired GFAP-positive glial phenotype or migrated toward the ischemic lesion forming glial scar. PSEN1 ΔE9 astrocytes did not impair behavioral recovery after experimental stroke.
Inferring Mechanisms of Auditory Attentional Modulation with Deep Neural Networks
Authors: Kuo Ting-Yu , Liao Yuanda , Li Kai , Hong Bo , Hu Xiaolin
Published: September 2022

Humans have an exceptional ability to extract specific audio streams of interest in a noisy environment; this is known as the cocktail party effect. It is widely accepted that this ability is related to selective attention, a mental process that enables individuals to focus on a particular object. Evidence suggests that sensory neurons can be modulated by top-down signals transmitted from the prefrontal cortex. However, exactly how the projection of attention signals to the cortex and subcortex influences the cocktail effect is unclear. We constructed computational models to study whether attentional modulation is more effective at earlier or later stages for solving the cocktail party problem along the auditory pathway. We modeled the auditory pathway using deep neural networks (DNNs), which can generate representational neural patterns that resemble the human brain. We constructed a series of DNN models in which the main structures were autoencoders. We then trained these DNNs on a speech separation task derived from the dichotic listening paradigm, a common paradigm to investigate the cocktail party effect. We next analyzed the modulation effects of attention signals during all stages. Our results showed that the attentional modulation effect is more effective at the lower stages of the DNNs. This suggests that the projection of attention signals to lower stages within the auditory pathway plays a more significant role than the higher stages in solving the cocktail party problem. This prediction could be tested using neurophysiological experiments.
“Good and Faithful Slave”
Authors: Manomi Dogara Ishaya
Published: September 2022

The parable of the talents in Matt 25:14–30 has been often interpreted using either the lens of social identity or virtue ethics, respectively. However, a careful integrative analysis indicates the intrinsic interrelation of social identity and virtue in four aspects. Through such an integration of social identity and the notions of virtue and the good life, Matthew redefines social identity for the Matthean in-group from a social status to a virtue status, from the quantity of one’s giftings to the quality of one’s character, and from a mere sense of belonging to a pursuit of human flourishing through virtue.
Alter vor Schönheit?
Authors: Schmidt Karl Matthias
Published: September 2022

The Second Epistle of Peter is one of those pseudepigraphs which are difficult to date. After a sketch of the problem, this article examines whether the Dialogus cum Tryphone of Justin Martyr or the Second Epistle to Timothy may provide information on the date of the Petrine epistle.
New taxonomic information of Cryphodera kalesari (Nematoda: Heteroderidae)
Authors: Singh Sorokhaibam Mexico , Singh Phougeishangbam Rolish , Singh Mayanglambam Ojit Kumar , Singh Samandram Sushilkumar , Couvreur Marjolein , Bert Wim , Meitei Naorem Mohilal
Published: September 2022

A population consisting of only second-stage juveniles of Cryphodera kalesari (Nematoda: Heteroderidae) was detected in the rhizosphere of bamboo in a forest in Mizoram state of India. New taxonomical information is provided for the juveniles, including the first light microscopy and scanning electron microscopy images. The juveniles are characterised by a body length of 0.3-0.4 mm, lateral field with three longitudinal incisures forming two areolated bands, a well-sclerotised and offset lip region with three lip annuli, a robust and strong stylet measuring 25-28 μm in length, anteriorly flat to slightly concave knobs, a secretory-excretory pore often at isthmus level, a conoid tail 47-52 μm long tapering to a narrow rounded terminus, a pore-like phasmid, and a distinct hyaline portion of the tail occupying roughly half of the tail length. The first molecular data of C. kalesari (sequences of 18S and D2-D3 of 28S rRNA genes and COI gene of mtDNA) were found to be almost identical to that of an unidentified Cryphodera sp. reported from Myanmar, Thailand and Vietnam, indicating that C. kalesari is widespread across south-east Asia.
The Protection of Displaced Persons from Ukraine in Portugal
Authors: de Sousa Constança Urbano
Published: September 2022

The war in Ukraine has caused a massive influx of people seeking protection in the European Union and has led to the activation, for the first time, of the Temporary Protection Directive. Although this influx mainly affects neighbouring countries, such as Poland and Romania, Portugal triggered, as early as 1 March 2022, the national temporary protection regime, thus granting immediate protection to people who were arriving because of the war. This article analyses this temporary protection regime, as well as the measures adopted to allow the rapid integration of those displaced persons, such as simplifying the recognition of professional qualifications, essential for their access to the labour market. Being special measures that only benefit citizens affected by the war in Ukraine, their compatibility with the constitutional principle of equality is questioned, as other foreigners equally affected by war and violation of human rights are excluded.
Disgraceful! Maimonides’ Use of Qabīḥ in the Guide
Authors: Harvey Steven
Published: September 2022

Maimonides (d. 1204) employs three different sets of terms for good and bad in his Guide of the Perplexed I, 2: one Hebrew set (from Gen. 3:5), ṭov and raʿ; and two Arabic sets, al-ḫayr and al-šarr, and al-ḥasan and al-qabīḥ. Guide I, 2 is one of the betterknown chapters of the book – one of the first chapters the beginning student of the Guide encounters and one whose important teachings have been the subject of many valuable studies. Curiously, leading translators and scholars do not see any meaningful distinction between the two sets of Arabic terms despite Maimonides’ well-known declaration that “the diction of this Treatise has not been chosen at haphazard” (see below, n. 19). This article seeks to understand and explain why Maimonides employs two different sets of Arabic terms here for the concepts of good and bad, with special focus on qabīḥ, a key term for him in this chapter and in others in the book.
Aristotle’s Political Theory as a Craft and Science in Politics 4–6
Authors: Inamura Kazutaka
Published: September 2022

This article maintains that Aristotle develops his political theory as a craft and science in Politics 4–6. The literature, however, has argued that he views political knowledge as a form of practical wisdom or prudence. This article discusses the way that Aristotle proposes political theory as a skill to help deal with unfavorable circumstances. In Greek political thought, craft and science are characterized as skills of cooperating with nature, taking up opportunities, and coping with uncertainty. Aristotle uses this conception when he develops his political theory in Politics 4–6. He understands that political theorists should advise prudent legislators on practical reforms of constitutions and help them address non-ideal situations. Serious efforts to gain causal knowledge are indispensable for statesmanship. This view of statesmanship better illustrates political theory as part of human efforts and cooperation to resolve uncertainty rather than the one that sharply distinguishes among theoretical, practical, and productive sciences.
New synonyms in the genus Diplectrona Westwood, 1840 from Southeast Asia (Hydropsychidae, Diplectroninae)
Authors: Mey Wolfram
Published: September 2022

Five new species described in the genus Diplectrona from Southeast Asia were found to represent synonyms of D. fasciata and D. pseudofasciata. The male genitalia of D. fasciata are illustrated for the first time.