bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex-specific transgenerational effects imposed by ancestral exposure to neonicotinoid thiacloprid in murine thyroid gland
Authors: Lahmidi Mariam Diba , Noc Morgane Le , Dali Ouzna , Kernanec Pierre-Yves , Merret Pierre-Etienne , Jaulin Christian , Smagulova Fatima
Published: September 2023

Background
Neonicotinoids, a relatively new widely used class of insecticide is used in agriculture to control insect populations.
Objectives
We examined the capacity of ancestral exposure to the neonicotinoid thiacloprid (thia) to induce transgenerational effects on thyroid tissue.
Methods
Pregnant outbred Swiss female mice were exposed to thia at embryonic days E6.5 to E15.5 using 0, 0.6, and 6 mg/kg/day doses. Thyroid paraffin sections were prepared for morphology analysis. We apply ELISA method to measure T4 and TSH levels, RT-qPCR for gene expression analysis, ChIP-qPCR techniques for sperm histone H3K4me3 analysis, and immunofluorescence microscopy and western blots for protein detection.
Results
We observed an alteration in the morphology of thyroids in both males and females in the F3 generation. We observed an increase in T4 hormone in F1 females and a significant T4 level decrease in F3 males. T4 changes in F1 females were associated with a TSH increase. We found that the amount of Iodothyronine Deiodinase 1 (DIO1) (an enzyme converting T4 to T3) was decreased in both F1 and F3 generations in female thyroids. GNAS protein which is important for thyroid function has increased in female thyroids. Gene expression analysis showed that the expression of genes encoding thyroid gland development, chromatin, biosynthesis and transport factors were affected in the thyroid gland in both sexes in F1 and F3. The analysis of sperm histone H3K4me3 showed that H3K4me3 occupancy at the Dio1 locus has decreased while Thyroglobulin (Tg) and Matrix Metallopeptidase 2 (Mmp2) genes have increased H3K4me3 occupancy in the sperm of F3 mice.
Conclusion
Our data suggest that ancestral exposure to thiacloprid affects thyroid function not only in exposed but also in indirectly exposed F3 generation.
Sustainability of Organic Farming from a Global Perspective: A Critical Analysis of Soil Types and Fertility Status of Organically Managed vs. Chemicalized Vegetable Fields of South India
Authors: George Nirmal Philip , Ray Joseph George
Published: September 2023

Aims: Globally, organic farming is emerging as a promising alternative to chemicalized agriculture in overcoming agricultural challenges. However, experts often question its efficiency in maintaining soil fertility to sustain the global demand for agricultural production. South India, characterized by its rich agricultural heritage and diverse agroecosystems, stands as a unique test ground for analyzing the problems and prospects of sustainable organic farming. Therefore, the primary goal of the current studywas to assess the soil fertility status of organic vegetable fields concerning various agroclimatic zones, soil types, seasons, organic practices, and vegetable crops in South India as a model for global comparisons.
Method: The approach was an assessment of soil quality parameters such as soil pH, total organic carbon (TOC), soil available nitrogen (SAN), soil available phosphorus (SAP), and soil available potassium (SAK) as the basis of soil fertility status and to compare the soil quality at different levels.
Results: The organic fields didn't exhibit distinctiveness in soil parameters from that of chemicalized fields except for soil-specific variations in some fields. Soil fertility status was at par with chemicalized fields in the region. The region does not consistently monitor nutrient levels concerning soil type, climate, or seasons. Different kinds of organic practiceshad no significant influence on soil quality.
Conclusion: The study highlights the need for global standardization of procedures in organizing organic agriculture as a sustainable model of agricultural production.
Design and Develop Function for Research Based Application of Intelligent Internet-of-vehicles Model Based on Fog Computing
Authors: KHUDHUR Abduladheem Fadhil , Kurnaz Sefer
Published: September 2023

In this research, an advanced Large Energy-Aware Fog (LEAF) computing based technique was introduced that allows for the modeling of large-scale vehicular network scenarios for executing thousands of streaming applications on a distributed, heterogeneous infrastructure. Compute nodes can be interconnected with different types of wired or wireless networking protocols, and edge devices can be mobile and join or leave the topology during the simulation. This level of realism permits research on energy-conserving fog computing architectures leading to more informed decisions in the planning of future infrastructure. Furthermore, the proposed model enables online decision making based on power usage, which can be used to implement energy-aware task placement strategies or routing policies. These algorithms can make direct use of LEAF’s ability to trace the power usage of infrastructure back to the responsible applications in order to identify and mitigate potential inefficiencies. Moreover, different kinds of energy-saving mechanisms can be integrated into simulations. What further distinguishes LEAF from existing fog computing simulators is the combination of analytical and numerical modeling approaches. Instead of modeling network traffic in detail, all data flows, and power models are represented by parameterizable, mathematical equations. This method leads to results that are easy to analyze and ensures scalability to hundreds or thousands of devices and applications with percentage of distance between 1 to 1000 was covered up to 98.75% using the LEAF technique. The research collects findings of various papers on the energy usage of different compute and networking equipment, including a detailed derivation of WAN connection parameters, to provide the reader with examples on how to model and parameterize LEAF experiments. Furthermore, the evaluation results indicate that fog computing may indeed be able to conserve energy in the future, mainly by reducing WAN usage.
Combined treatment for a rare malignant glomus tumor of the esophagus with pulmonary and liver metastases: a case report and review of literature
Authors: Liu Yanan , Mao Jingjing , Shen Dongfeng , Jin Baoli , Feng Wuxue , Du Wenjing
Published: September 2023

Background:
Glomus tumors are typically benign soft tissue tumors that occur at the extremities; malignant and viscerally occurring cases are extremely rare.
Case Presentation:
We report a 49-year old male patient with a malignant esophageal glomus tumor that was complicated by lung and liver metastases. Genetic test results guided the patient's individualized treatment. Consequently, treatment with Anlotinib combined with Tislelizumab achieved significant clinical benefits.
Conclusion:
Our case report demonstrates that immunotherapy combined with anti-angiogenic therapy in patients with malignant esophageal glomus tumors can achieve significant efficacy and suggests the potential value of Next-Generation Sequencing(NGS) detection in guiding personalized treatments in patients with malignant esophageal glomus tumors.
Community bylaws concerning sexual and reproductive health and rights in Machinga district, Malawi: To what extent are they responsive to young people’s needs?
Authors: Kok Maryse , Munthali Alister , Mvula Peter , Chisiza Zindaba , Mat Marielle Le
Published: September 2023

Background
Community bylaws are commonly accepted mechanisms to influence behaviour change to achieve better health and development outcomes in sub-Saharan Africa. However, the uses, benefits, and potential downsides of community bylaws are largely unclear, especially regarding sexual and reproductive health and rights (SRHR) of young people. The objective of this study was to determine the extent to which community bylaws in Machinga district in southern Malawi are responsive to young people’s realities and SRHR needs.
Methods
In Phase 1 of this qualitative study, 35 community members were interviewed, including 14 young people (15–24 years), five parents, five traditional leaders, and eleven key informants. Based on findings from Phase 1, eleven members from local youth groups co-created a drama performance that covered issues concerning bylaws and young people’s SRHR (Phase 2). The drama was performed in the community, after which young women (18–24 years), young men (17–24 years), female and male parents discussed on what they saw in the drama, focusing on young people’s SRHR, in four focus group discussions (Phase 3). All transcripts were coded and thematically analysed and narratives were written on main themes.
Results
Three community SRHR bylaws, related to teenage pregnancy, child marriage, and sexual harassment and rape were identified and commonly accepted in the community. While these bylaws intend to reduce SRHR-related issues among young people, they are often not involved in bylaw formulation. The bylaws were associated with protection of girls, and a good reputation for boys, young men and traditional leaders. Bylaw enforcement faced problems, as fines were not in line with national laws, and wealthy offenders could avoid them through bribes. Effects of bylaws on teenage pregnancy rates seemed limited, while some positive effects on school readmission, prevention of child marriage, and reporting sexual harassment were reported.
Conclusions
The study revealed that community bylaws were accepted but not owned by young people, and had different effects on the rich versus the poor, and girls versus young men. Bylaws were associated with punishment in terms of money, which seemed to overpower their potential to promote rights and address social norms underlying SRHR issues of the youth.
Synthesis and characterization of nonmetal-doped TiO 2 nanoparticles for mineralization of rhodamine B dye
Authors: Karimi Maryam , Grayeli Alireza
Published: September 2023

A novel series of C-, N-, and F-doped TiO2 photocatalysts were fabricated using a simple sol-gel method, utilizing 4-(trifluoromethyl) nicotinic acid (TFNA) as a precursor for carbon, nitrogen, and fluorine doping. The resulting materials were characterized using different advanced techniques such as X-ray Diffraction (XRD), Diffuse Reflectance Spectroscopy (DRS), Raman spectroscopy, Fourier Transform Infrared Spectroscopy (FT-IR), Transmission Electron Microscopy (TEM), and Field Emission Scanning Electron Microscopy (FESEM). The synthesis approach involved the creation of nanoparticles with varying weights of TFNA, ranging from 0.3 wt% to 1.6 wt%, followed by calcination at ambient temperature. The resulting nanostructures were then tested for their efficiency in degrading rhodamine B (RhB) dye under ultraviolet (UV) light irradiation.The experimental findings revealed that the 1.6 wt% TFNA/TiO2 composite exhibited exceptional photocatalytic activity, with approximately 87.0% degradation efficiency towards RhB dye in aqueous solutions under UV light. This remarkable performance can be attributed to the increased lifetime of photogenerated electron-hole pairs and accelerated interfacial charge transfer rates.
An antibody ordered assembly functional BPE-ECL platform for aflatoxin B1 detection
Authors: Qiao Fanglin , Jiang Yanjun , Chen Yin , Xu Mingyao , Xiong Xiaohui , Liu Yuanjian
Published: September 2023

Due to the complex characteristics of food matrix, inaccurate results are likely to occur when using traditional methods to detect Aflatoxin B1 (AFB1). In this paper, a biosensor based on closed bipolar electrode (BPE) has been developed to detect highly toxic AFB1 in mycotoxins. The biosensor uses cathode of closed BPE as a functional sensing interface and anode as a signal collection interface. On the functional sensing interface, monoclonal antibody connecting AFB1 at the top of DNA tetrahedron structure. In the presence of horseradish peroxidase (HRP), hydrogen peroxide (H2O2) catalyzes the oxidation of 4-chloro-1-naphthol (4-CN) to produce insoluble precipitations (4-CD). AFB1 competes with HRP-AFB1 to bind monoclonal antibody, resulting in a decrease in the content of HRP involved in catalytic oxidation reactions and a synchronous reduction in precipitations produced. Due to the electron transfer is influence by precipitation capacity, the decrease in precipitations lead to an increase in the BPE anode luminescence signal. On the signal collection interface, AFB1 detection is achieved by measuring the ECL strength of the [Ru(bpy)3]2+/TPA system. Through the above methods, the target does not need to participate in the ECL reaction of the anode, avoiding the direct contact between the photoactive molecules and the complex food matrix. The analysis shows that the relative deviation from ELISA is between − 4.5 ~ 9.8%, indicating that there is no significant difference between the biosensor and ELISA. The BPE-ECL sensor exhibits high sensitivity and specificity in detecting AFB1, with a linear range of 0. 01–40 ng mL− 1 and a detection limit of 3 pg mL− 1. It can be further applied to the detection of different kinds of toxins and has broad application prospects.
Self-efficacy, grit, and rural career aspirations among early career nurses: A repeated cross-sectional study
Authors: Terry Daniel , Peck Blake , Baker Ed , Schmitz David
Published: September 2023

Background: The present global nursing workforce shortage represents an impediment to the delivery of safe, evidence-based healthcare. Despite all collective efforts a consistent stream of nurses leaving the profession remains, particularly within the first five years of practice, further exacerbated in rural communities.
Methods: As part of a longitudinal investigation examining early career nurse career trajectories, changes in self-efficacy, grit, and career aspirations were compared, using a repeated cross-sectional design, among second- and fourth-year nurses after graduation. Participants included, 117 (response rate 52.2%) who completed an online questionnaire 18-24 months after graduating, and 32 participants (response rate of 21.0%) who agree to repeat the questionnaire 36-48 months after graduating. The questionnaire included demographic and employment items, and measures examining general and occupational self-efficacy, grit, and rural career aspirations.
Results: No differences between general and occupational self-efficacy or grit were identified between send and fourth year nurses. In addition, the importance placed on undertaking rural career also remains unchanged. However, a higher proportion of fourth year nurses were more likely to be in management or were considering leaving the profession, as anticipated.
Conclusions: This examination of early career nurses who are now in their second and fourth-year post-graduation highlights self-efficacy, grit, and rural career aspirations remains stable between two- and four-years following graduation, while nursing in their fourth year were more likely to consider leaving the profession. Nursing retention is a ‘Wicked Problem’ that is unavoidably a complex amalgam of macro, meso and micro factors that we are yet to fully appreciate.
Whole Genome Resequencing Reveals the Evolutionary History and Geographic Isolation of the eastern Asian Hickory (Carya)
Authors: Zhang Da , Yang Rui-Feng , Chen Jia-Hui , Pan Lang-Bo , Duan Wei , Zhang Qi-Xiang , Xia Guo-Hua , Huang Youjun
Published: September 2023

Background
The biogeographic characteristics of disjunctive distribution play a crucial role in plant geography and understanding mechanisms related to endangerment. Genome sequencing offers an opportunity to explore genetic relationships, population dispersal, and the floristic evolution of disjunctively distributed flora. In this study, we conducted comprehensive whole-genome deep resequencing of EA Carya to elucidate their evolutionary history and the factors contributing to disjunctive distribution.
Results
After conducting high-depth sequencing of five EA Carya species and filtering the data, we obtained a dataset comprising 3,869,439 high-quality SNPs. The phylogenetic analysis of the entire Carya revealed two monophyletic clades, separating EA Carya from NA Carya. Population genetic analysis indicated that C. kweichowensis, an endangered species, exhibited the lowest nucleotide diversity and the earliest divergence among the studied EA Carya species. Through selection elimination analysis, we identified a set of adaptive genes in C.hunanensis characterized by the highest nucleotide diversity and the widest distribution compared to other EA Caryaspecies. These genes were primarily associated with mitochondrial function and alkaloid biosynthesis. Additionally, species distribution modeling predicted the suitable habitat for the five EA Carya species, revealing the potential distribution of the endangered C. kweichowensis. Importantly, our analysis indicated minimal spatial overlap in distribution regions among EA Carya species during different time periods.
Conclusions
The results of population historical dynamics combined with climate and geological changes support the hypothesis that EA Carya migrated from NA to Europe during the Paleogene or Eocene and continued their migration to Asia, subsequently moving eastward until reaching EA. The uneven regional distribution of EA Carya is believed to be a consequence of Quaternary climate fluctuations, mountain barriers hindering species dispersal, and the limited cold tolerance of these trees. EA Carya highlight the significant role of climate and geological changes in their regional distribution and migration routes in Asia. Furthermore, the discovery of potential habitats offers a promising avenue for the conservation of C. kweichowensis.
Th17/Treg balance is restored during the suppression of experimental autoimmune encephalomyelitis treated by Astragalus polysaccharides via the microbiota-gut-brain axis
Authors: Ma Jinyun , Lu Qijin , Zhao Yan , Liu Xiaojun , Ding Guiqing , Wang Yuanhua , Wang Xiaohan , Chen Yuxin , Zhang Tong , Cheng Xiaodong
Published: September 2023

The Th17/Treg imbalance is an important cause of immune cell infiltration into the central nervous system (CNS) and subsequent neuroinflammation, demyelination, and neurodegeneration in multiple sclerosis (MS). Increasing attention has been given to the role of the microbiota-gut-brain axis in MS pathogenesis. The gut microbiota affects the Th17/Treg balance in the gut as well as in distal areas, such as the CNS, which further contributes to the onset and progression of MS. Our previous studies have shown that Astragalus polysaccharide (APS) has a role in alleviating the clinical symptoms and demyelination of experimental autoimmune encephalomyelitis (EAE) mice, a classic MS model. However, the mechanism of action is not fully understood. In this study, we found that APS suppressed inflammation and regulated the Th17/Treg balance in the CNS and peripheral blood of EAE mice. It was further shown that APS inhibited gut inflammation and reduced Th17 function. The experiment with an antibiotic cocktail interfering with the gut microbiota proved that APS alleviated EAE by regulating the gut microbiota. Through 16S rRNA sequencing, we showed that APS regulated gut microbiota diversity and composition in EAE mice. Then, we found that APS regulated metabolite composition in feces and plasma, thus altering gut and blood metabolic functions. The neuroactive ligand‒receptor interaction pathway was enriched in both fecal and plasma metabolites. Metabolites related to this pathway, including sphingosine 1 phosphate (S1P), prostaglandin E2 (PGE2), ADP, and ATP, were downregulated by APS. The levels of bile acid metabolites such as taurochenodeoxycholate-7-sulfate and N-palmitoyl aspartic acid were upregulated by APS. In summary, our study demonstrated that APS exerts a suppressive effect on EAE by regulating gut microbiota composition, affecting metabolite composition, and improving the Th17/Treg balance in the peripheral blood and CNS.
Laparoscopic versus open distal gastrectomy for advanced gastric cancer in elderly patients：a propensity‑score matched analysis
Authors: Yao Qing , Sun Qian-Nan , Wang Dao-Rong
Published: September 2023

Background
Scarce research has reported the efficacy and safety of laparoscopic distal gastrectomy in elderly patients. This retrospective study aimed to compare the outcomes of laparoscopic and open distal gastrectomy for advanced gastric cancer in elderly patients.
Methods
A total of 303 elderly patients who underwent distal gastrectomy for advanced gastric cancer from June 2017 to June 2021 were enrolled. Variables used to calculate propensity score matching included sex, age, body mass index, American Society of Anesthesiologists, history of diabetes, and history of hypertension. The statistical significance of continuous variables was tested using an independent sample t test. Chi-square or Fisher exact tests were used for categorical variables. Kaplan–Meier curve and log-rank test were used to the evaluation of 3-year overall survival and recurrence-free survival.
Results
After performing 1:1 propensity score matching, 248 patients were included for analysis (laparoscopic = 124, open = 124). Compared with the open group, the laparoscopic group showed significant advantages in estimated blood loss (P < 0.001), pain scale on the first postoperative day (P = 0.002), time to first flatus (P = 0.004), time to first liquid diet (P = 0.005), hospital stays (P < 0.001), and total complications (P = 0.011), but devoted much more operation (P < 0.001). No statistical difference was observed between the two groups in 3-year recurrence-free survival (P = 0.315) or overall survival (P = 0.159).
Conclusions
Our analysis demonstrated that laparoscopic surgery had the advantages of less intraoperative blood loss, fewer postoperative complications, and faster postoperative recovery in elderly patients who underwent distal gastrectomy for advanced gastric
Parturition Effects on Sociality and Dynamic Interactions of Female White-tailed Deer
Authors: Haus Jacob , Dion Justin , Webb Stephen , Rogerson Joseph , Bowman Jacob
Published: September 2023

Background
Female white-tailed deer (Odocoileus virginianus) typically form matriarchal social groups throughout much of the year; however, little research has examined the effect of parturition on sociality. We used measures of dynamic interaction, a function of travel direction and displacement, to examine social interactions between adult females before and after parturition. We monitored parturient, free-ranging individuals on a 126-ha property using vaginal implant transmitters linked to GPS collars during a 2-month period surrounding peak parturition (1 May–30 June 2016). We calculated local dynamic interaction (di; cohesiveness of movement for each time step) and global dynamic interaction (DI; cohesiveness of movement throughout the study period) metrics for all female pairs with overlapping 95% kernel density home range estimates (n = 29 interaction pairings).
Results
Global DI was correlated positively with home range overlap (%). Mean local di values indicated moderate social cohesion within the population prior to parturition. Following parturition, mean local di values declined below zero suggesting avoidance among female pairs with overlapping ranges. Mean local di began to increase approximately 15 days postpartum but did not return to prepartum levels during our study period (~ 25 days postpartum).
Conclusions
The changes in female social dynamics following parturition are likely a trade-off among several factors such as neonate mobility, predator avoidance, and nutritional demands. However, the trends we observed are to be expected given the life history of female deer around parturition in which sociality declines around parturition and then returns gradually to pre-parturition levels.
Pleural effusion with high adenosine deaminase is not always tuberculous pleurisy
Authors: Choe Junsu , Shin Sun Hye , Jeon Kyeongman , Huh Hee Jae , Park Hyung-Doo , Jeong Byeong-Ho
Published: September 2023

Background: Adenosine deaminase (ADA) is a useful biomarker for the diagnosis of tuberculous pleurisy (TBP). However, pleural effusions with high ADA can also be caused by other diseases, particularly hematologic malignant pleural effusion (hMPE).
This study aimed to investigate the factors that could differentiate TBP and hMPE in patients with pleural effusion ADA ≥ 40 IU/L.
Methods: This was a retrospective observational study of patients with pleural effusion ADA ≥ 40 IU/L, conducted at a Korean tertiary referral hospital with an intermediate tuberculosis burden between January 2010 and December 2017. Multivariable logistic regression analyses were performed to investigate the predictors associated with TBP and hMPE, respectively.
Results: Among 1134 patients with ADA ≥ 40 IU/L, 375 (33.1%) and 85 (7.5%) were diagnosed with TBP and hMPE, respectively. TBP and hMPE accounted for 59% (257/433) and 6% (27/433) in patients with ADA between 40 and 70 IU/L, respectively. However, in patients with ADA ≥ 150 IU/L, they accounted for 7% (9/123) and 19% (23/123), respectively. When ADA between 40 and 70 IU/L was the reference category, ADA between 70 and 150 IU/L was independently associated with TBP (adjusted odds ratio [aOR], 3.11; 95% confidence interval [CI], 1.95–4.95; P <0.001). ADA ≥ 150 IU/L was negatively associated with TBP (aOR, 0.35; 95% CI, 0.14–0.90; P = 0.029) and positively associated with hMPE (aOR, 13.21; 95% CI, 5.67–30.79; P<0.001). In addition, TBP was independently associated with lymphocytes ≥ 35% and a lactate dehydrogenase (LD)/ADA ratio < 18 in pleural effusion. hMPE was independently associated with pleural polymorphonuclear neutrophils < 50%, thrombocytopenia, and higher serum LD.
Conclusion: In patients with high levels of pleural effusion ADA, hMPE should be considered. Several markers in pleural effusion and serum may help to more effectively differentiate TBP from hMPE.
A Mortality Prediction System for Neonatal Jaundice Using Machine Learning Techniques
Authors: Bhadouria Aashi Singh
Published: September 2023

Birth complications, especially jaundice, are a leading cause of child death and morbidity across the world. The severity of these diseases may decrease if researchers learn more about their origins and develop effective treatments. Certain advancements have been made, but they are insufficient. Newborns often have jaundice as their primary medical issue. Jaundice may be brought on by a variety of factors. An elevated bilirubin level is a hallmark of jaundice. The incidence of hyperbilirubinemia in newborns is highest during the first postnatal week. The inability to detect problems early enough to get prompt treatment, as well as the similarity of symptoms that may lead to misdiagnosis, are both potential causes of failure. The situation is far worse for Ethiopia and other countries already in distress. A lack of paediatricians and neonatologists might be a reason for alarm. Due to a lack of appropriate diagnostic tools, experts in newborn health are often forced to rely their judgements only on interviews. It's probable the interviewer didn't know much about contagious diseases in infants. This suggests there is room for a faulty or insufficient diagnosis. For machine learning to make accurate forecasts, sufficient amounts of relevant past data must be made available. Jaundice has a high mortality rate, however this may be reduced with prompt identification and classification. The diagnostic accuracy of illnesses may be enhanced by using machine learning techniques. In this essay, I do a deep dive into medical data mining and pull out all the stops to provide you the information you need. It is necessary to investigate, analyse, extract, choose, and categorise the characteristics. Finally, it offers some therapeutic ideas. It helps the doctor diagnose jaundice faster so that effective therapy may be started sooner. The procedure is simplified and made more natural with the use of computer vision and machine learning methods. The refined method of classification improves accuracy. Using a classification stacking method, we found that the top causes of mortality in newborns include serious infections, birth asphyxia, necrotizing enterocolitis, and respiratory distress syndrome. Most infant fatalities may be traced back to these three factors. Dates included in the data set are 2018 through 2021. Support Vector Machine (SVM) performed best when pitted against the newly developed stacking model, XGBoost (XGB), Random Forest (RF), and other machine learning models. The proposed stacking model performed better than its competitors in terms of accuracy (97.04 percent). This is important because we hope it will help hospitals, particularly those with less resources, detect infant diseases sooner.
Therapeutic Targeting Tongue Squamous Cell Carcinoma via ICAM1 Antibody-Drug Conjugates in Preclinical Models
Authors: Guo Peng , Ma Letao , Lu Ye , Dai Yujie , Yang Teng , Yang Yuxuan , Shimura Takaya , Sha Chulin , Li Xinfang , Fang Jianmin , Zheng Weihui
Published: September 2023

To date, the treatment options for metastatic and recurrent tongue squamous cell carcinoma (TSCC) remain limited due to the lack of effective drug targets and therapeutics. Here we report the identification of ICAM1 as a TSCC target candidate for the development of antibody-drug conjugates (ADC), an emerging class of targeted therapeutics. We first performed an unbiased and quantitative screening of a panel of 69 TSCC cell surface antigens that identified ICAM1 as the most abundant hit. The overexpression level of ICAM1 was validated in 26 TSCC clinical specimens and four cell lines along with genomic information of 153 TSCC patients from the TCGA database. Subsequently, two ICAM1-targeted ADCs were designed and synthesized using two cytotoxic payloads of different mechanisms of action: monomethyl auristatin E (MMAE), a microtubule inhibitor, and deruxtecan (DXd), a type I DNA topoisomerase inhibitor, respectively. The therapeutic efficacy of these ICAM1 ADCs was determined in vitro and in vivo. Both ADCs selectively and potently ablate TSCC tumors in the established SAS cell line and patient-derived xenograft models. Our experimental results strongly support ICAM1 as a promising ADC target candidate for TSCC therapy.
Dihydrofolate Reductase (DHFR) Inhibition Promotes Ferroptotic Cell Death Through Nrf2 Suppression to Enhance Radiosensitivity In Pancreatic Ductal Adenocarcinoma (PDAC) Cells
Authors: Xue Jiao , Ma Jiayan , Duan Jingjing , Wu Zhongliang , Xia Wei , Tao Jialong , Zhu Wei , Zhu Yaqun , Peng Qiliang , YU Chenxiao , Gu Ying
Published: September 2023

Pancreatic cancer is one of the most aggressive and fatal malignancies of the digestive system. Radiotherapy plays an important role for local control of locally advanced, unresectable pancreatic cancer (LAPC). Given that the application of radiotherapy is restricted by radiation resistance of pancreatic cancer, radiosensitizers hold promise to overcome pancreatic ductal adenocarcinoma (PDAC) radioresistance and improve patient outcomes. Our research demonstrated that high dihydrofolate reductase (DHFR) expression correlates with poorer survival in pancreatic cancer, associated with transcriptional reprograms regulating proliferation and DNA repair. Methotrexate, an inhibitor of DHFR, sensitizes PDAC cell lines to ionizing radiation, reducing clonogenicity and proliferation, and synergistically triggering robust ferroptotic cell death via Nrf2 pathway inhibition. Our findings unveil a novel therapeutic perspective leveraging synergistic oxidative damage and deregulated metabolism to confront radioresistance in PDAC.
Evaluation of clinical characteristics and risk factors associated with Chlamydia psittaci infection based on metagenomic next-generation sequencing
Authors: yuan lei , 陈 嫱 , zhu yu , 赖 兰敏 , Zhao Rui , Liu Yang
Published: September 2023

Introduction
This study aimed to evaluate the clinical characteristics, imaging examination, laboratory examination and treatment options of Chlamydia psittaci associated pneumonia, as well as the risk factors affecting the progress of Chlamydia psittaci pneumonia, in order to improve the effect of therapeutics.
Methods
We retrospectively analyzed the clinical data of patients with chlamydia psittaci associated pneumonia in the First Affiliated Hospital of Nanchang University from January 2021 to December 2021. The patient's past medical history, clinical manifestations, laboratory examinations, chest CT findings, treatment status, and prognosis data were collected.
Results
All cases of Chlamydia psittaci in our research have been confirmed by mNGS. Among 46 cases of Chlamydia psittaci pneumonia, Poultry exposure was reported in 35 cases. In severe cases of Chlamydia psittaci pneumonia, Neutrophils, Procalcitonin(PCT), Lactate Dehydrogenase(LDH), Hydroxybutyrate Dehydrogenase(HBDH), Creatine Kinase Isoenzymes-B(CK-MB) and D-Dimer levels were remarkably higher than that of non-severe cases, except for lymphocytes(all P < 0.05). Chest CT scans showed Bilateral, multiple lobar lungs, pleural effusions involvement in those suffering from severe Chlamydia psittaci pneumonia(P < 0.05). Multivariate analysis revealed that higher lymphocyte(OR 0.836, 95% CI 0.714–0.962, P = 0.041) was the only protective factor for survival. Despite the difference in alpha diversity between the severe and mild groups of Chlamydia psittaci pneumonia, the slight difference was not significant. There were notable differences between the two pathogens, including Streptococcus australis and Streptococcus pneumoniae(P < 0.05).
Conclusion
Metagenomic next-generation sequencing (mNGS) is an effective detection method for the early diagnosis and selection of appropriate antibiotics for Chlamydia psittaci pneumonia.
Correlation between the Size of Cervical Ossification of the Posterior Longitudinal Ligament and Bone Mineral Density
Authors: Kwak Kyu Wan , Park Yoon Ghil , Park Jinyoung
Published: September 2023

Objective
Bone mineral density (BMD) has been shown to increase in patients with ossification of the posterior longitudinal ligament (OPLL). However, the correlation between the OPLL size and BMD has not been studied yet. This study aimed to investigate the correlation between the size of the OPLL and BMD.
Methods
This cross-sectional study enrolled 84 patients who underwent cervical OPLL surgery and preoperative examinations with both computed tomography (CT) and dual-energy X-ray absorptiometry (DXA) between January 2015 and March 2021. The maximal OPLL occupying the cervical spine lesion (levels C2–7) was identified from axial images of the preoperative cervical spine CT scans, and the anterior-posterior diameter, area of the cervical spinal canal, and OPLL were measured at this location. BMD was measured in the lumbar spinal levels L1–4, femoral neck, trochanteric area, intertrochanteric area, and total femur area using DXA.
Results
The average OPLL-occupying diameter ratio of the cervical spine positively correlated with the average Z-score of the lumbar spine (r = 0.22, P < 0.05). The average OPLL-occupying area ratio of the cervical spine was positively correlated with the average T-score and Z-score of the lumbar spine (r = 0.22, P < 0.05 and r = 0.24, P < 0.05, respectively).
Conclusion
The axial size of the cervical OPLL is positively correlated with the BMD of the lumbar spine. Since the underlying mechanism of OPLL development remains unknown, these findings may improve the understanding of its pathogenesis.
Relationship between anxiety and problematic smartphone use in first-year junior high school students: moderated mediation effects of physical activity and school adjustment
Authors: Cao Mei , Yang Haibo , Chen Duanduan
Published: September 2023

Background and aims
Despite previous research identifying anxiety as a risk factor for problematic smartphone use among students, the mediating and moderating mechanisms underlying the relationship between the two aforementioned variables are poorly understood. This study aims to explore the relationship between anxiety and problematic smartphone use among first-year junior high school students, together with the mediating effects of school adjustment and the moderating effects of physical activity on the mentioned relationship.
Method
This study was conducted using a Web-based self-report questionnaire survey with data collected from 445 first-year junior high school students in Jinan City, Shandong Province. Mediation and moderation analyses were performed using the PROCESS macro in SPSS.
Results
The results showed that anxiety predicted problematic smartphone use not only directly but also indirectly via school adjustment. School adjustment played a partial mediating role in the relationship between anxiety and problematic smartphone use. Physical activity also played a moderating role in the relationship between anxiety and school adjustment.
Conclusion
School adjustment and physical activity may be important variables in the relationship between anxiety and problematic smartphone use.
Learning complex representations from spatial phase statistics of natural scenes
Authors: MaBouDi HaDi , Subramani Krishna , Soltanian-Zadeh Hamid , Amari Shun-ichi , Shimazaki Hideaki
Published: September 2023

Natural scenes exhibit higher-order statistical structures encapsulated within their spatial phase information, contributing significantly to visual perception and neural coding. Despite this potential, comprehending the brain's adept representation of phase information and developing computational models to capture these processes remain areas of limited advancement. To address this gap and facilitate the capture of spatial phase patterns within the efficient coding hypothesis framework, we introduce a novel generative model for the representation of the phase images of visual scenes. We propose that images can be deconstructed into complex-valued features and independent source signals while integrating their non-uniform phase distributions. Expanding upon existing bilinear generative models, we provide a gradient-based optimization algorithm for estimating model parameters, firmly rooted in the principles of maximum-likelihood. Additionally, we introduce a technique to decorrelate the elements of each complex source signal. Through extensive simulations, we showcase the model's superiority in blind source separation of complex-valued signals compared to conventional models. The application of our model to amplitude-shuffled natural scenes, which preserves spatial phase statistics but loses amplitude information, uncovers learned complex features reminiscent of the receptive fields of visual cortex simple cells, characterized by distinct pairs of Gabor-like filter profiles. These findings emphasize the model's capacity to enhance goodness-of-fit beyond the limitations of models of natural scenes with uniform phase assumptions, shedding new light on how spatial phase patterns are encoded. Our findings highlight the significance of structured phase information within natural signals, further strengthening the proposition that phase-sensitive cells in the visual cortex play a fundamental role in reducing redundancy in the phase information of natural scenes.
Analytical model of interface crack in bonding quasi-brittle material between distinct elastic media
Authors: Kaminsky Anatoly , Dudyk Mykhailo , Chornoivan Yuri
Published: September 2023

The purpose of this work is to build an analytical model of an interfacial crack in piecewise homogeneous elastic bodies to predict the conditions of its initiation. The treatment is based on the concept of the process zone, which takes into account the existence of a local region with a high level of stresses and strains in the bonding material before the crack front. In the process zone, a quadratic strength criterion of the Mises-Hill type is assumed. The use of this criterion provides consideration of the quasi-brittle mechanism of the bonding material fracture. Using the Mellin integral transformation, the problem of calculating the parameters of the process zone in the bonding material at the tip of the interfacial crack within the framework of the proposed model is reduced to a vector functional equation, for which an exact analytical solution was found using the Wiener-Hopf method. From the solution found, a closed system of transcendental equations and relationships is derived for determining the length of the process zone, the phase angle of the load, and the energy release rate in the zone and the opening of the crack at its tip, which form an accessible algorithm for estimating the limit loads that precede propagation of the crack along the interface. Numerical analysis of the developed model is performed, and the possibility of its application in fracture studies of some composite materials is demonstrated.
Japanese preschool-aged children’s gratitude as a moral virtue: Is the development of gratitude culture-specific?
Authors: Kato-Shimizu Mayuko , Hinobayashi Toshihiko
Published: September 2023

The function of gratitude as a factor in forming reciprocal relationships has not yet been examined in preschool-aged children. This study examines how cultural differences may influence children’s expression and understanding of gratitude. Two vignettes involving a high- and low-cost situation of expressing gratitude were told to Japanese preschool-aged children, and their responses to the scenarios were recorded. Compared to American children, a certain number of Japanese children associated positive feelings with the benefactor when they helped, would help the benefactor if they were in need, and cited reciprocity as a reason for doing so. The findings confirmed that the sprouting of gratitude as a moral virtue is also observed in preschool children from non-Western countries, and commonalities in moral development across cultures were found. At the same time, depending on the cost incurred by the benefactor on offering help, we found cultural differences in various aspects of gratitude. The findings suggested that gratitude, which encompasses the norm of reciprocity, is triggered in Japanese children in response to the cost to the benefactor.
Temperature sensitive nanogel-stabilized pickering emulsion of fluoroalkane for ultrasound guiding vascular embolization therapy
Authors: Li Ling , Cao Yanyan , Zhang Haining , Zheng Min , Xing Jun , Zheng Chuansheng , Zhao Yanbing , Yang Xiangliang
Published: September 2023

X-ray imaging technologies, including CT, DSA and so on, are widely used in transcatheter arterial embolization (TAE) therapy on hepatocellular cancer (HCC) clinically. They still have some disadvantages, such as complex operation, ionizing radiation and others, though have high imaging contrast. Ultrasound imaging, which has the advantages of simple and fast operation, no ionizing radiation and real-time imaging, likely plays an important role on the field of medical diagnosis. Here, Poly (N-isopropylacrylamide-co-2,2,3,4,4,4-Hexafluorobutyl methacrylate) (PNF) nanogels were synthesized for stabilizing the Pickering emulsion of 2H, 3H-decafluoropentane (HDFP) named TGFPE. The emulsion had abilities of thermosensitive sol-gel transition and long-term ultrasound imaging in vitro. It was be conformed that the emulsion could achieve vascular embolization and long-term ultrasound imaging in vivo according to the results of the experiments of animal TAE therapy model. The flow and accumulation of the emulsion droplets were visualized under guidance of ultrasound imaging. In summary, the Pickering emulsion has potential to be used as ultrasound-guided embolization material for mediating TAE surgery.
The brain-bone marrow axis: Implications for chronic traumatic brain injury and age-related neurodegeneration
Authors: Wu Junfang , Ritzel Rodney , Li Yun , Jiao Yun , Doran Sarah , Khan Niaz , Henry Rebecca , Brunner Kavitha , Loane David , Faden Alan , Szeto Gregory
Published: September 2023

Introduction: It is well established that traumatic brain injury (TBI) causes acute and chronic alterations in systemic immune function and that systemic immune changes contribute to posttraumatic neuroinflammation and neurodegeneration. However, how TBI affects bone marrow (BM) hematopoietic stem cells/progenitors chronically and to what extent such changes may negatively impact innate immunity and neurological function has not been examined. Methods: To further understand the role of BM cell derivatives on TBI outcome, we generated BM chimeric mice by transplanting BM from chronically injured or sham (i.e., 90 days post-surgery) congenic donor mice into otherwise healthy, age-matched, irradiated hosts. Immune changes were evaluated by flow cytometry, multiplex ELISA, and NanoString technology. Moderate-to-severe TBI was induced by controlled cortical impact injury and neurological function was measured using a battery of behavioral tests.
Results: TBI induced chronic alterations in the transcriptome of BM lineage-c-Kit+Sca1+ (LSK+) cells in wild type (WT) mice, including modified epigenetic and senescence pathways. After 8 weeks of reconstitution, no changes in BM or blood leukocyte number or composition were observed in TBI→WT chimeric mice compared to either SH→WT or non-irradiated WT control mice, suggesting normal engraftment. However, peripheral myeloid cells from TBI→WT mice showed significantly higher oxidative stress levels and reduced phagocytic activity, consistent with previous findings in WT TBI mice. TBI→WT mice also showed higher plasma concentrations of chemokines and displayed significant deficits in neurological function. At eight months after reconstitution, TBI→WT chimeric mice were leukopenic, with continued altered phagocytosis and oxidative stress responses, as well as persistent neurological deficits. NanoString gene expression analysis revealed BM-driven changes in neuroinflammation and neuropathology after 8 weeks and 8 months of reconstitution, respectively. Chimeric mice subjected to TBI at 8 weeks and 8 months post-reconstitution showed that longer reconstitution periods (i.e., time post-injury) were associated with increased microgliosis and leukocyte infiltration. Pre-treatment with a senolytic agent, ABT-263, significantly improved behavioral performance of aged mice at baseline, although it did not attenuate neuroinflammation in the acutely injured brain.
Conclusion: TBI causes chronic activation and progressive dysfunction of the BM stem/progenitor cell pool, which drives long-term deficits in hematopoiesis, innate immunity, neurological function, as well as altered sensitivity to subsequent brain injury