bluuebunny/crossref_metadata_2025 huggingface dataset:
An Explainable machine learning model for predicting response to targeted therapy and immunotherapy in advanced hepatocellular carcinoma: a multicentric study
Authors: Zhang Jin-Xing , Yan Hai-Tao , Fan Wen-Long , Wei Juan , Liu Sheng , Shi Hai-Bin , Cheng Yuan , Feng Zun-lei , Zu Qing-Quan
Published: November 2024

Background and aims Combination therapy based on targeted therapy and immunotherapy is a first-line treatment for advanced hepatocellular carcinoma (HCC). However, accurately predicting tumor response to the combination therapy is challenging. We aimed to develop an explainable machine learning model to predict response to the combination therapy in advanced HCC.
Methods Patients with advanced HCC who received targeted therapy combined with immunotherapy at four tertiary hospitals were enrolled between January 2020 and January 2024. The extreme gradient boosting (XGBoost) model was constructed to predict whether patients would respond to the combination therapy. The area under the receiver operating characteristic curve (AUC) and F1 score were used to evaluate the predictive performance of the XGBoost model. The SHapley Additive exPlanations (SHAP) method was deployed to interpret the XGBoost model.
Results A total of 179 patients were enrolled in this study, and seventy-six patients (42.5%) showed a response to the combination therapy. The XGBoost model had an AUC of 0.795 (95% confidence interval: 0.716–0.873) and a F1 score of 0.704 for predicting the response to the combination therapy for advanced HCC in the training set. The importance of SHAP variables in the XGBoost model ranked from high to low, was: interventional therapy, portal vein tumor thrombus, extrahepatic metastasis, number of tumors, and age.
Conclusion The XGBoost machine learning model shows high performance in predicting response to targeted therapy combined with immunotherapy in advanced HCC. Additionally, the SHAP method facilitates a comprehensive interpretation of the results generated by the machine learning model.
Healthcare-Seeking Intentions of Middle-Aged and Elderly Individuals with Critical Diseases in Taiwan During the COVID-19
Authors: Lee Po-Chun , Huang Ching-Yuan , Hsu Meng-Jun
Published: November 2024

Background
The COVID-19 pandemic has posed a significant threat to global public health. Over the past decade, Taiwan has experienced an aging population, with mortality rates from illnesses rising each year. During the pandemic, middle-aged and elderly patients with critical diseases were often reluctant to seek medical care due to fear of infection, potentially impacting disease control, health monitoring, and quality of life. Understanding the healthcare-seeking behavior of middle-aged and elderly patients with critical diseases during the pandemic is crucial for improving healthcare accessibility and reducing mortality rates.
Methods
This study applied the Theory of Planned Behavior (TPB) as the foundational framework, incorporating three main constructs: “attitude,” “subjective norm,” and “perceived behavioral control.” Additionally, two more constructs, “perceived risk” and “trust,” were included to explore the healthcare decision-making “behavioral intentions” of critical disease patients during the COVID-19 pandemic. Using a cross-sectional study design and purposive sampling, a total of 526 valid questionnaires were collected, and the structural equation model was verified using Partial Least Squares (smart PLS).
Results
Among the five primary dimensions influencing patients’ healthcare decision-making "behavioral intentions," “trust” was found to have the most significant impact, followed by “attitude,” “perceived risk,” “perceived behavioral control,” and “subjective norm.” All secondary dimensions within the five primary dimensions were shown to significantly affect "behavioral intentions" through mediating effects. Additionally, the three common causes of critical diseases—hypertension, hyperglycemia, and hyperlipidemia—were found to have a positive and significant impact on "behavioral intentions."
Conclusion
The expanded Theory of Planned Behavior used in this study provides a theoretical framework for understanding health behavior decision-making processes, effectively explaining the "behavioral intentions" of middle-aged and elderly patients with critical diseases in seeking healthcare during the COVID-19 pandemic.
ACR combined with PPS to treat lumbar degenerative diseases: a retrospective study
Authors: Yan Xiaobing , Feng Dapeng , Chu Jin , Li Zhengwei
Published: November 2024

Study Design. Retrospective study to investigate the benefits of ACR for lumbar degenerative diseases (LDD).
Objective. Investigate the outcomes of anterior column realignment(ACR) combined with percutaneous pedicle screw fixation(PPS) and differ for transforaminal lumbar interbody fusion (TLIF) for LDD.
Methods.
From June 2018 to December 2021, 22 consecutive patients with LDD underwent ACR. At the same time while 22 patients underwent TLIF. Preoperative and intraoperative parameters of all the patients are collected. The influences of ACR on mechanical factors and indirect decompression were evaluated by radiological parameters. Function improvements are assessed by Oswestry Disability Index (ODI), Visual Analogue Score (VAS) and Japanese Orthopaedic Association (JOA) Scores during one year of follow-up.
Results.
Preoperatively, there was no significant difference of age, sex, body mass index (BMI), ODI, VAS and JOA scores in both groups . Compared with ACR group, TLIF group had increased hospital stay (6.77±3.25 days vs. 5.0±1.11 days, P<0.05), blood loss (645.45±571.95ml vs. 235.45±78.30ml, P<0.05) and postoperative drainage (391.82±364.84 ml vs. 0 ml, P<0.001). ACR could significantly improve the radiological parameters. The short-term scores of function and pain of ACR group were higher than TLIF group.
Conclusion.
Both of ACR and TLIF could effectively resolve the symptoms of LDD. Compared with TLIF, ACR had a better improvement of short-term outcomes. ACR could be performed and improved as optional treatment strategy for LDD.
Predicting pragmatic language abilities from brain structural MRI in preschool children with ASD by NBS-Predict
Authors: Qian Lu , Ding Ning , Fang Hui , Xiao Ting , Sun Bei , Gao HuiYun , Ke XiaoYan
Published: November 2024

Pragmatics, as it pertains to spoken language, plays a crucial role in effectively conveying messages across various social communication contexts. This aspect is frequently highlighted in the challenges experienced by children diagnosed with autism spectrum disorder (ASD). Notably, there remains a paucity of research investigating how the structural connectome (SC) predicts pragmatic language abilities within this population. Using diffusion tensor imaging (DTI) and deterministic tractography, we constructed the whole-brain white matter structural network (WMSN) in a cohort comprising 92 children with ASD and 52 typically developing (TD) preschoolers, matched for age and gender. Subsequent graph theoretical analyses were conducted to assess alterations in the global and node-based properties of the WMSN within both cohorts. To further elucidate these findings, we employed NBS-Predict, a novel methodology that integrates machine learning (ML) with network-based statistics (NBS), to identify dysconnected subnetworks associated with ASD. Our application of NBS-Predict allowed us to predict pragmatic language abilities based on the SC derived from the whole-brain WMSN in the ASD group. Initially, NBS-Predict identified a subnetwork characterized by 42 reduced connections across 37 brain regions (p = 0.01), achieving a highest classification accuracy of 79.4% (95% CI: 0.791–0.796). The dysconnected regions were predominantly localized within the brain’s frontotemporal and subcortical areas, with the right superior medial frontal gyrus (SFGmed.R) emerging as the region exhibiting the most extensive disconnection. Moreover, NBS-Predict demonstrated that the optimal correlation coefficient between the predicted pragmatic language scores and the actual measured scores was 0.204 (95% CI: 0.181–0.226). This analysis revealed a significant association between the pragmatic language abilities of the ASD cohort and the white matter connections linking the SFGmed.R with the bilateral anterior cingulate gyrus (ACC). In summary, our findings suggest that the subnetworks displaying the most significant abnormal connections were concentrated in the frontotemporal and subcortical regions among the ASD group. Furthermore, the observed abnormalities in the white matter connection pathways between the SFGmed.R and ACC may underlie the neurobiological basis for pragmatic language deficits in preschool children with ASD.
Evaluation of imputation strategies for multi-centre studies: Application to a large clinical pathology dataset
Authors: Grigoroff Lucy , Masuda Reika , Lindon John , Kadyrov Janonna , Nicholson Jeremy Kirk , Holmes Elaine , Wist Julien
Published: November 2024

As part of a strategy for accommodating missing data in large heterogeneous datasets, two Random Forest-based (RF) imputation methods, missForest and MICE were evaluated along with several strategies to help them handle the inherent structure of the dataset. Background: A total of 3817 complete cases of clinical chemistry variables from a large-scale, multi-site preclinical longitudinal pathology study were used as an evaluation dataset. Three types of ‘missingness’ in various proportions were artificially introduced to compare imputation performance for different strategies including variable inclusion and stratification. Results: MissForest was found to outperform MICE, being robust and capable of automatic variable selection. Stratification had minimal effect on missForest but severely deteriorated the performance of MICE. Conclusion: In general, storing and sharing datasets prior to any correction is a good practise, so that imputation can be performed on merged data if necessary.
Macular ganglion cell complex layer thickness measured with spectral-domain OCT in a large population-based cohort study
Authors: Lin Caixia , Wu Jian , Lv Aiguo , Liu Hongyi , Pan Qing , Cao Kai , Jia Xu , Fan Sujie , Wang Ning Li
Published: November 2024

Purpose: To establish the normal GCC thicknesses profile in the general population using SD-OCT in different macular sectors. To determine the systemic and ophthalmic factors associated with GCC thickness and further identify the potential risk factors were the secondary objective.
Methods: Participants in the population-based cohort study had to be at least thirty years old. Every participant had a routine ophthalmological examination. Using SD-OCT, the GCC thickness was determined. To assess the relationship between GCC thickness and systemic and ocular characteristics, mixed linear models were used. R V.4.1.1 was the statistical analysis program utilized.
Results: 2490 subjects average age of 56.60 ± 10.39 years were collected in this analysis. GCC average thickness measured was 95.57±7.47μm. GCC thickness of the superior(95.46±7.87μm) was the thinnest, and the inferior subfield(95.68±7.66μm) was thickest. In univariate and multivariate regression models，thinner GCC thickness was significantly associated with older age (P < 0.001), absence of smoking (P = 0.002), higher SBP (P < 0.001) and DBP (P < 0.001), more diabetes (P<0.001), higher HbA1c (P<0.001), lower HDL (P=0.001), higher LDL (P=0.011), coronary heart disease (P < 0.001), history of coronary heart disease (P = 0.007), lower IOP (P = 0.198), higher spherical equivalent (P = 0.009), and better BCVA (P < 0.001).
Conclusions: When diagnosing non-glaucoma patients, it is important to take into account the variation in GCC thickness throughout the Chinese community. In the meantime, the thickness of GCC is tightly associated to several ocular and systemic variables. Our results also highlighted the necessity of creating normative databases globally, as well as demonstrating ethnic disparities in GCC thickness and the uniqueness of related ocular and systemic variables.
How does job dissatisfaction fuel nurse exit, voice, loyalty, and neglect (EVLN) behaviors? A Cross-sectional Survey
Authors: Li Jackie Zhanbiao , Chen Ming , Lao Yingqian , Hu Wanqin
Published: November 2024

In organizational behavior, job dissatisfaction has become an essential factor in shaping employees’ responses, including exit, voice, loyalty, and neglect (EVLN) behaviors, impacting workplace dynamics and outcomes. This study is based on a questionnaire survey investigating EVLN behaviors resulting from job dissatisfaction among nurses in public hospitals in Chongqing. The aim is to identify the underlying reasons for nurse shortages driven by job dissatisfaction. To begin with, drawing on Farrell's EVLN behavior framework and utilizing dynamic game theory, this study examines how nurse job dissatisfaction influences exit, voice, loyalty, and neglect behaviors. The findings reveal that nurse job dissatisfaction is positively correlated with exit and neglect behaviors, while negatively correlated with voice and loyalty behaviors. And then, a subsequent heterogeneity analysis shows that the effects of job dissatisfaction on EVLN behaviors are fully heterogeneous in terms of gender and education level, and partially heterogeneous in terms of age and marital status. Additionally, dynamic game theory is applied to study the internal evolution of EVLN behaviors triggered by job dissatisfaction. The results indicate that nurses typically choose loyalty behavior initially; however, if dissatisfaction persists, they shift to voice behavior. If voice behavior is not addressed, nurses either directly opt for exit behavior or transition to exit behavior through neglect. Finally, the study discusses the implications of these findings for medical policymakers, hospital managers, and practitioners.
Novel Model of Childhood Appetitive Traits in Children with Obesity
Authors: Thaker Vidhu , Nigam Sunaina , Zhu Mengqi , Shoemaker Ashley , Gross Amy , Fox Claudia
Published: November 2024

Background/Objectives:
Appetitive traits have a central role in energy intake and development of obesity. Child Eating Behavior Questionnaire (CEBQ) is a validated psychometric tool to measure appetitive traits in children. This study sought to assess the CEBQ factor structure in children with obesity. We hypothesized that hedonic traits are more prominent with obesity and in older children.
Subjects/Methods:
This cross-sectional observational study used CEBQ data from three geographically diverse centers in children with obesity. Eight known CEBQ subscales and the established factor model were compared by severity of obesity, age and sex. Exploratory factor analysis (EFA) to define the appetitive trait factor structure was undertaken in a training dataset and validated in a test set.
Results:
Children with obesity (n=814) showed higher food response, enjoyment of food, emotional overeating and desire to drink compared to population-based controls (p < 0.001) that correlated with obesity severity. The EFA identified a novel six-factor model with a new “Food avidity” factor that explained 15.8% of the variance. Satiety responsiveness (p < 0.001) and emotional undereating (p = 0.03) were lower in youth over six years compared to younger, while food fussiness and food avidity were the same, without any sex differences.
Conclusions:
CEBQ is useful to assess appetitive traits in children with obesity. The novel factor structure in youth with obesity suggests that temporal or phenotypic differences necessitate a revision of the established factor model. The new factor structure may be used to develop a hyperphagia questionnaire.
Prevalence and predictive factors of concurrent cervical spinal cord compression in patients with osteoporotic vertebral compression fractures
Authors: Lei Shuao , Chen Runsen , Zhang Pengxin , Li Guangzhou , Wang Qing
Published: November 2024

Purpose: This study aims to investigate the incidence, clinical features, and predictors of cervical spinal cord compression (CSCC) in patients with osteoporotic vertebral compression fractures (OVCF).
Methods: The study focused on patients with OVCF. The presence of CSCC was determined using the modified Cord Compression Index (Grades 0–3) based on the magnetic resonance imaging (MRI) of the entire spine. Significant CSCC was defined as Grade≥2, and the distribution of compression level as well as the number of Grade≥2 segments were investigated in each patient. Predictive factors for CSCC were identified using multivariate regression analysis, with variables including sagittal parameters from MRI of the entire spine and general patient characteristics.
Results: Out of 300 OVCF patients, 121 (40.3%) displayed significant CSCC on MRI. Of these, 106 were grade 2, and 15 were grade 3. Signal changes indicating myelomalacia were detected in 12 patients (4.0%) on T2-weighted MRI images. Of the 121 patients, 107 (88.4%) were asymptomatic or had subtle myelopathy, while 71 (58.7%) had multiple segmental compressions. The incidence of CSCC was positively correlated with age. Significant CSCC was most frequently found in the C4/5 and C5/6 segments. Only 4 patients (4.0%) underwent percutaneous kyphoplasty (PKP) combined with cervical decompression and fusion surgery under general anesthesia in the one stage. Multivariate regression analysis identified age, gender, body mass index (BMI), and Torg-Pavlov ratio as independent predictors of CSCC grade.
Conclusion: The prevalence of significant cervical spinal cord compression in OVCF patients was 40.3%, which is relatively high. In patients with older age, female sex, elevated BMI, or developmental spinal stenosis, preoperative cervical spine MRI and assessment for myelopathy signs and symptoms are essential to prevent adverse treatment outcomes. Prophylactic cervical decompression and general anesthesia should not be prioritized unless the patient has severe cervical spinal cord compression or local anesthesia is insufficient for PKP, as this approach is generally more beneficial for the patient.
M1 macrophage-derived exosomal miR-20b promotes radiosensitization in HPV + HNSC
Authors: Liu Huan , Zhang Siwei , Li Wanlin , Liu Zengchen , Gong Tingdan , Duan Siyu , Liu Tianyang , Tong Fangjia , Pan Shuang , Wei Lanlan
Published: November 2024

Background
Human papillomavirus (HPV) is a significant risk factor for head and neck squamous cell carcinoma (HNSC). M1 macrophages enhance the radiosensitivity of HPV+ HNSC. Research has demonstrated that M1 macrophage-derived exosomes (M1 exos) possess a more potent anti-tumor function, and these exosomes serve as crucial mediators of communication between tumor cells and the tumor microenvironment. However, the role of M1 exos in the radiation sensitivity of HNSC remains unclear.
Materials and Methods
HPV status and macrophage infiltration levels in the tissues of 25 HNSC were evaluated using IHC. M1 macrophages were induced and cultured in vitro, and exosomes were extracted through differential ultracentrifugation. The effect of M1 macrophage exosomes on the radiotherapy sensitivity of HPV+ HNSC was investigated using an in vitro co-culture system. The expression level of γ-H2AX was assessed by immunofluorescence. Data from TCGA and GEO databases were utilized to evaluate the levels of miR-20b in HNSC and its relationship with radiotherapy sensitivity and prognosis. Additionally, the radiosensitivity of SCC090 cells overexpressing miR-20b was assessed through cell experiments to determine the functional role of miR-20b. Finally, bioinformatics methods were employed to elucidate the mechanism by which miR-20b enhances radiotherapy sensitivity.
Results
In HPV+ HNSC, M1 macrophages were highly infiltrated and played a crucial role in enhancing the sensitivity of HPV+ HNSC to radiotherapy. M1 exos infiltrated HPV+ HNSCC, increasing their sensitivity to radiation. Meanwhile, M1 macrophages were abundant in miR-20b than M2 macrophages, and the radiation sensitivity of HPV+ HNSC was significantly increased by transfecting them with a miR-20b mimic. The target genes of miR-20b were involved in DNA damage repair and cell cycle regulation. By analyzing the function of the target genes, CCND1 was identified as a key gene through which miR-20b enhanced radiotherapy sensitivity in HPV+ HNSC.
Conclusion
In this study, our data suggest that M1 exos, enriched with miR-20b, regulate the DNA damage repair pathway in tumor cells by targeting CCND1, thereby enhancing the sensitivity of tumors to radiotherapy. Consequently, miR-20b may represent a potential therapeutic strategy for HNSC.
Experiences and Reflections of Doctors on the Operations of Designated Clinics during the COVID-19 Pandemic in Hong Kong: a Qualitative Study
Authors: Zhang Dingzuan , Tang Kin Sze , Lau Phyllis
Published: November 2024

Background
The conversion of General Out-patient Clinics (GOPC) into COVID-19 designated clinics played a crucial role in combating COVID-19 pandemic in Hong Kong in 2022. This qualitative research used an interpretive phenomenological approach and aimed to contribute valuable perspectives from doctors on the operations of designated clinics for the preparedness of future outbreaks and health emergencies.
Methods
Participants were purposively recruited from the doctors who worked in designated clinics during the COVID-19 pandemic in the Cluster of New Territories West, Hong Kong. Individual semi-structured interviews were conducted using an interview guide informed by the researchers’ past experiences and the Donabedian framework. The verbatim transcripts were imported into NVivo 12 for data organizing, coding and thematic analysis.
Results
Sixteen participants were recruited and interviewed until data sufficiency. Eight themes were elicited and grouped under the three domains of the Donabedian framework: structure (availability of facilities, supportive training and education, and flexible manpower allocation), process (challenges in clinical practices, communication and collaboration, and effectiveness of operations), and outcome (patient outcomes and impact to healthcare workers).
Conclusions
Overall, participants thought that the operations in the designated clinics were smooth, efficient, and achieving satisfactory outcomes. However, improvements could be made in upgrading facilities to better manage more severe future outbreaks, enhancing government roles in information centralization and public communication and improving collaboration between designated clinics and ambulance services. This research provided valuable insights for the preparedness of future outbreaks and health emergencies.
Economic freedom and private domestic investment in sub-Saharan Africa
Authors: Dia Ibrahima , Ouedraogo Idrissa
Published: November 2024

This study investigates the effect of economic freedom on private domestic investment in Sub-Saharan Africa. Unlike the existing literature, it specifically focuses on the SSA region and considers the effect of the five components of the Fraser Institute's Index of Economic Freedom on private domestic investment. To this end, we use a panel of 41 SSA countries over the period 2000–2021 using the system GMM estimation method. The results show that economic freedom favors private domestic investment through the size of government, the legal system and property rights, as well as the regulation of the credit, labor and business markets. Conversely, the freedom to trade internationally has a negative effect. These results imply that SSA countries should enhance the size and quality of public investments, strengthen their legal frameworks, ease restrictions on capital flows and tariff barriers, and create a favorable regulatory environment for businesses to stimulate private investment.
JEL classification : C82, E22, O43, O55, P16
Association of childhood and adulthood socioeconomic status with frailty index trajectories: using five-wave panel data from the China Health and Retirement Longitudinal Study (CHARLS) Article title：European Journal of Ageing
Authors: Zhang Kai , Chai Lirong , Zhang Yi , Wang Weijing , Hu Xiaolin , Kong Weizheng , Zhang Dongfeng , Fan Junning
Published: November 2024

Background: The relationship between childhood and adulthood socioeconomic status (SES) and long-term frailty trajectories is unclear. We aimed to assess the frailty index (FI) dynamic trajectories and examine the associations between childhood and adulthood SES and frailty trajectories.
Methods: We included 7321 participants aged 45 and older from the 2011-2020 China Health and Retirement Longitudinal Study (CHARLS). Six childhood SES factors and four adulthood SES factors were included. Group-based trajectory modelling was used to identify frailty trajectories and multinomial logistic regression was used to assess the association between SES and frailty trajectories.
Results: Three frailty trajectory groups were identified: low-increase trajectory (LT, 59.9%), moderate-increase trajectory (MT, 31.7%) and high-increase trajectory (HT, 8.4%). With the LT group as reference, for childhood SES, participants with an illiterate mother (relative-risk radio [RRR]=1.67, 95% confidence interval [CI]: 1.10-2.52), having not enough food (1.67, 1.34-2.09), with family’s financial situation (2.35, 1.61-3.42) and childhood health status (2.72, 2.09-3.53) worse than others had higher odds of being in the HT group. And for adulthood SES, rural residence (1.86, 1.50-2.31), with an educational level of less than middle school (2.75, 1.83-4.15), had higher odds of being in the HT group. Similar results were found for people of different ages and genders.
Conclusions: Participants with lower SES, including maternal and self- low education, childhood hunger, worse family financial and childhood health status are more likely to experience a high-increase FI trajectory, i.e. aging faster. Attention should be paid to reduce early-life social inequalities thus to promote later-time healthy aging.
Probing the Meissner effect in pressurized bilayer nickelate superconductors using diamond quantum sensors
Authors: Yu Xiao Hui , Wen Junyan , Xu Yue , Wang Gang , He Ze-Xu , Chen Yang , Wang Ningning , Lu Tenglong , Ma Xiaoli , Jin Feng , Chen Liucheng , Liu Miao , Fan Jing-Wei , Liu Xiaobing , Pan Xin-Yu , Liu Gang-Qin , Cheng Jinguang
Published: November 2024

Recent reports on the signatures of high-temperature superconductivity with a critical temperature Tc close to 80 K have triggered great research interest and extensive follow-up studies1-8. Although zero-resistance state has been successfully achieved under improved hydrostatic pressure conditions3,9, there is no clear evidence of superconducting diamagnetism in pressurized La3Ni2O7-δ due to the low superconducting volume fraction and limited magnetic measurement techniques under high pressure conditions10. Here, using shallow nitrogen-vacancy centers implanted on the culet of diamond anvils as in-situ quantum sensors, we observe convincing evidence for the Meissner effect in polycrystalline samples La3Ni2O7-δ and La2PrNi2O7: the magnetic field expulsion during both field cooling and field warming processes. The correlated measurements of Raman spectra and NV-based magnetic imaging indicate an incomplete structural transformation related to the displacement of oxygen ions emerging in the non-superconducting region. Furthermore, comparative experiments on different pressure transmitting media (silicone oil and KBr) and nickelates (La3Ni2O7-δ and La2PrNi2O7) reveal that an improved hydrostatic pressure conditions and the substitution of La by Pr in La3Ni2O7-δ can dramatically increase the superconductivity. Our work clarifies the controversy about the Meissner effect of bilayer nickelate and contributes to a deeper understanding of the mechanism of nickelate high-temperature superconductors.
Cancer Immunotherapy Using AIRE Conditioning of the Tumor Epitopeome
Authors: Vile Richard , Pulido Jose , Chen Alex , Kendall Benjamin , Tonne Jason , Metko Muriel , Thompson Jill , Sangsuwannukul Thanich , Yerovi Maria Chiriboga , Diaz Rosa , Webb Mason , Huff Amanda , Moore Madelyn , Schuelke Matthew , Irshad Sheeba , Appleton Elizabeth , Melcher Alan
Published: November 2024

T cell immune tolerance is established in part through the activity of the Auto-immune Regulator (AIRE) transcription factor in the medullary Thymic Epithelial Cells (mTEC) of the thymus. AIRE induces expression of SELF peripheral tissue-specific antigens for presentation to naïve T cells to promote activation/deletion of potentially autoreactive T cells. We show, for the first time to our knowledge, that tumors mimic the role of AIRE in mTEC to evade immune rejection. Thus, by expressing a broad range of SELF epitopes against which minimal functional T cell reactivities exist because of thymic deletion, AIRE acts as a master controller of SELFNESS, effectively cloaking the tumor from T cell attack. Moreover, we describe a completely novel immunotherapy in which engineered changes in AIRE expression in tumor cells alters their profile of SELFNESS, exposing both AIRE-modified, and parental unmodified, tumor cells to T cell attack. Consistent with our studies, patient RNAseq shows expression of AIRE predicts response to immune therapies with a strong correlation between AIRE expression and markers of TCR signaling. Therefore, by re-setting the immunological SELFNESS of cancer cells, this novel AIRE-mediated immunotherapy 1). converts a highly tolerized T cell compartment into a heteroclitic tumor-reactive T cell population; 2) confers de novo sensitivity to immune checkpoint blockade upon non-immunogenic tumors; 3). completely removes the need to identify potentially immunogenic tumor-associated antigens as targets for generation of de novo CD8+ and helper CD4+ T cell responses; and 4) leads to potent T cell-mediated rejection of aggressive, immunologically cold, non-immunogenic tumors.
SIRT4-mediated deacetylation of PRDX3 attenuates liver ischemia reperfusion injury by suppressing ferroptosis
Authors: Chen Sanyang , Yu Qiwen , Yang Dongjing , Ran Binli , Pan Jie , Song Yaodong , Cui Mengwei , Mei Chaopeng , Wang Haifeng , Li Huihui , Li Guanghui , Meng Yinuo , Wang Fazhan , Guo Wenzhi , Zhu Changju
Published: November 2024

Liver ischemia-reperfusion injury (LIRI) is an important cause of the clinical prognosis of liver transplantation. Despite the diverse roles that Sirtuin 4 (SIRT4) plays in posttranslational modifications, its specific involvement in the onset and progression of LIRI remains unclear. The aim of this research was to investigate the influence of SIRT4 on the pathogenesis of LIRI. In this study, SIRT4 knockout and liver-specific overexpression mice and AML12 cells were used to investigate the possible role of SIRT4 in LIRI. Here, we showed that SIRT4 expression was downregulated in mice with LIRI or AML12 cells exposed to H/R injury and in the liver tissue of liver transplant patients. SIRT4 deletion led to the exacerbation of liver injury and ferroptosis; conversely, liver-specific SIRT4 overexpression in mice produced the opposite results. Furthermore, the ferroptosis inhibitor ferrostatin-1 counteracted the exacerbation of liver injury and ferroptosis caused by SIRT4 knockout. Mechanistically, SIRT4 interacted with Peroxiredoxins (PRDX3) and deacetylated it at lysine 92, leading to the inhibition of PRDX3 hyper-oxidation and ferroptosis. Furthermore, the protective effect of SIRT4 on LIRI was dependent on the deacetylation of PRDX3 at K92. Finally, we developed a liver-targeted Lipid nanoparticles (LNP)-sirt4 mRNA that alleviated liver I/R injury and ferroptosis in mice. Taken together, these results indicate that the SIRT4‒PRDX3 axis plays a key role in the progression of LIRI and may be a therapeutic target for the treatment of LIRI.
A combined soft X-ray and theoretical investigation discloses the water harvesting behaviour of Mg MOF-74 at the crystal surface
Authors: D'Angelo Paola , Tavani Francesco , Tofoni Alessandro , Vandone Marco , Busato Matteo , Braglia Luca , Torelli Piero , Stanzione Maximillian G. , Armstrong Robert , Morris Russell , Colombo Valentina
Published: November 2024

Metal-organic frameworks (MOFs) are receiving growing interest as permanently porous, highly tunable materials for real-world atmospheric water harvesting applications. Although it is becoming clear that surface effects are key to initiating and regulating MOF water uptake, obtaining molecular-level details on this issue has proven to be elusive. Here, we present a novel methodology based on ambient pressure soft X-ray absorption spectroscopy, machine learning-assisted theoretical spectroscopy and molecular dynamics (MD) simulations to gain quantitative and selective insights into the structural and dynamical behaviour of water confined at a MOF crystal surface. We applied our combined experimental and theoretical method to investigate the properties of wa- ter at the surface of Mg-MOF-74, while obtaining complementary information on the water uptake and release from the bulk by synchrotron powder X-ray diffraction. MD simulations and state-of-the-art theoretical simulations of the spectroscopic data were then employed to describe the water/MOF interface with molecular detail, evidencing that water molecules directly bound to the framework Mg sites first give rise to one-dimensional water chains by establishing a dense hydrogen-bond network with an additional water molecule per metal site, and subsequently nucleate porous channel filling, with the water layers found in the center of the MOF channels exhibiting higher mobility and reduced reorientational ability. The developed method can inform the rational optimization of MOF interfaces for water harvesting.
Novel expanded ATXN10 alleles in the healthy Peruvian population: a matter of Indigenous American ethnic origin
Authors: Milla-Neyra Karina , Araujo-Aliaga Ismael , Manrique-Enciso Carla , Sarapura-Castro Elison , Illanes-Manrique Maryenela , Saldarriaga-Mayo Ana , Medina-Colque Angel , Rios-Pinto Julia , Cornejo-Herrera Ivan , Rivera-Valdivia Andrea , Mata Ignacio , Loesch Douglas , Lozano-Vasquez Leonel , Bordia Tanuja , O’Connor Timothy , Schüle Birgitt , Cornejo-Olivas Mario
Published: November 2024

Spinocerebellar ataxia type 10 (SCA10) is a neurodegenerative disease predominant in Latin American individuals with Indigenous American ancestry. SCA10 is caused by an expansion of ATTCT repeat within the ATXN10 gene. Healthy individuals carry 9-32 ATTCT repeats, whereas SCA10 patients carry an expansion of 280 repeats and higher. Recently, expanded alleles (>32 repeats) have been identified in healthy Peruvian Indigenous American individuals, with unclear significance. This study aims to characterize the variability of the ATTCT repeats within the ATXN10 gene across self-declared Indigenous American and Mestizo subpopulations from Peru. A total of 871 samples (754 Mestizo and 117 Indigenous American) were analyzed using PCR, and RP-PCR when suspecting apparent homozygosity due to expanded alleles. 8.7% of the total of healthy individuals (76/871) carry at least an expanded allele. The 14-repeat allele being the most common for both subpopulations (41.5%). Expanded alleles were detected in the Peruvian population (4.5%) with a significantly higher frequency among self-declared Indigenous American compared to Mestizo, suggesting a possible association with the ethnic origin. The G allele at the SNP rs41524547 had a frequency of 51.39% in individuals with expanded alleles, with not significantly difference between subpopulations. Further analysis should be performed to confirm the size and composition of ATTCT repeat tract, as well as the contribution of rs41524547 in SCA10.
In silico evolution of globular protein folds from random sequences
Authors: Koonin Eugene , Sahakyan Harutyun , Babajanyan Sanasar , Wolf Yuri
Published: November 2024

The origin and evolution of protein folds are among the most challenging, long-standing problems in biology 1,2. Although many plausible scenarios of early protein evolution leading to fold nucleation have been proposed 3-8, realistic simulation of this process was not feasible because of the lack of efficient approaches for protein structure prediction, a situation that changed with the advent of powerful tools for fast and robust protein structure prediction, such as AlphaFold 9,10 and ESMFold11. We developed a computational approach for protein fold evolution simulator (PFES) with atomistic details that provide insights into the mechanisms of evolution of globular folds from random amino acid sequences. PFES introduces random mutations in a population of protein sequences, evaluates the effect of mutations on protein structure, and selects a new set of proteins for further evolution. Repeating this process iteratively allows tracking the evolutionary trajectory of a changing protein fold that evolves under selective pressure for protein fold stability, interaction with other proteins, or other features shaping the fitness landscape. We employed PFES to show how globular protein folds could evolve from random amino acid sequences as monomers or in complexes with other proteins. The simulations reproduce the evolution of many simple folds of natural proteins as well as the evolution of distinct folds not known to exist in nature. We show that evolution of a stable fold from random sequences, on average takes 3 to 8 amino acid replacements per site, suggesting that simple but stable protein folds can evolve relatively easily. These findings could shed light on the enigma of the rapid evolution of protein fold diversity at the earliest stages of life evolution. PFES tracks the complete evolutionary history from simulations that describes intermediate states at the sequence and structure levels and can be used to test versatile hypotheses on protein fold evolution.
Morphological Trait Correlations and Nutrient Compositions of the Japanese moon scallop Ylistrum japonicum in China
Authors: Xie Yaoyu , Han Yida , Wang Xubo , Tian Ying , Chang Yaqing
Published: November 2024

The present study focuses on the scallop Ylistrum japonicum, a species with significant economic and ecological value, to evaluate its morphological traits and the nutritional composition of the adductor muscle. A total of 150 individuals were collected from the coastal area near Hailing Island, Guangdong Province, South of China. Measurements included shell length, width, height, wet weight, soft body weight, gonad weight, and adductor muscle weight. The study employed multiple regression analysis and path analysis to investigate the relationships between body size traits and quality traits. These results indicate a strong positive correlation among the morphological and weight-related traits, with some variation in the strength of correlation depending on gender. In the selective breeding of Y. japonicum, there should be a focus on indirectly improving weight traits by selecting for morphological traits, which serves as an important basis for selective breeding. Nutritional components of the adductor muscle were analyzed for moisture, ash, fat, protein, fatty acids and amino acids. The nutritional composition analysis of the adductor muscle provided insights into its protein, amino acid and fatty acid content, which are essential for evaluating the scallop as a food source. The study's findings contribute to the understanding of Y. japonicum's quality traits and nutritional value, laying a basis for the development of selective breeding strategies aimed at boosting the species' aquaculture potential.
The impact of vaping on the health of children and adolescents
Authors: Ishbuldina A. V. , Vakhitov Kh. М. , Gaichik Е. А.
Published: November 2024

The article discusses the issue of the use of vape pens and electronic cigarettes, particularly among children and teenagers. The authors analyzed 58 scientific articles that discuss the damage to the lungs caused by smoking electronic devices, in order to identify symptoms and pathological changes. The study highlights the various clinical manifestations of lung damage associated with vaping and using electronic cigarettes (EVALI, e-cigarettes or vaping-associated lung injuries), and the need for a differential diagnosis with other respiratory illnesses, including COVID-19. It is essential to conduct educational and awareness campaigns in society to spread information about the risks of using electronic devices. Further research is needed to understand the long-term effects of vape pens and e-cigarettes on human health.
Evaluation of the effectiveness of probiotic bacteria Bifidobacterium BB-12 and Streptococcus thermophilus TH-4 in the prevention of microecological and gastrointestinal disorders in children born by cesarean section
Authors: Nikolaeva I. V. , Shaikhieva G. S. , Gaynatullina L. R.
Published: November 2024

The clinical and laboratory effectiveness of a biocomplex of probiotic bacteria (Bifidobacterium BB-12, Streptococcus thermophilus TH-4) in preventing the development of microecological and gastrointestinal disorders in children born by cesarean section has been studied. A prospective open comparative study was conducted. The main group consisted of 16 healthy newborns born by cesarean section who were treated with a probiotic (Bifidobacterium BB-12, Streptococcus thermophilus TH-4) at 1 dose once a day. Oral administration of the probiotics began immediately after delivery and continued for 14 days. A control group of 21 healthy babies born by caesarian section who did not receive the probiotics during the study period was also included. Bacteriological analysis of fecal samples and assessment of the health status were performed at the ages of 4–5 days, 1 month, and 3 months. In children receiving probiotics, the incidence of infantile intestinal colic was lower at the age of 1 month, opportunistic microflora were less frequently isolated (p<0.01), and signs of inflammation in the intestines were less often detected during the follow-up period, as shown by a coprological study.

Conclusion. The effectiveness of using probiotics (Bifidobacterium BB-12 and S. thermophilus TH-4) to prevent microecological and gastrointestinal problems in children born by cesarean section has been demonstrated.
Clinical significance of determining the level of citrulline in children who have undergone intestinal resection during the neonatal period
Authors: Druzhkova E. E. , Kamalova A. A. , Sageeva G. I. , Podshivalin A. A.
Published: November 2024

Citrulline is an amino acid that is not found in protein and does not enter the body through food, enteral or parenteral nutrition. It is instead synthesized exclusively by enterocytes. Therefore, citrulline concentrations in the blood can reflect the process of biosynthesis in the intestines and are directly related to changes in the function of these cells.

Purpose. The aim of the study was to assess citrulline levels in children who had undergone intestinal resection during the neonatal period.

Material and methods. The study included 22 children with short bowel syndrome, diagnosed by a doctor (main group; average age 3.7 months). We also included 20 children who had undergone surgery to remove less than 50% of their intestine but did not have short bowel syndrome (comparison group; average age 3 months 1 day). The control group consisted of 23 healthy children who had never had surgery on their gastrointestinal tract and did not have any congenital malformations or clinical signs of enteropathy (average age 5 months 3 days). High performance liquid chromatography-mass spectrometry (HPLC-MS) was used to measure the level of citrulline.

Results. The average level of citrulline in the blood of children in the main group was 18 μmol/l (95% CI 10–22.8), in the comparison group – 17.5 μmol/l (95% CI 16–21), in the control group – 26 μmol/l (95% CI 22–3). Citrulline levels in patients who underwent surgery in the neonatal period were significantly different from those of children in the control group There were no differences in the content of citrulline between the main and comparison groups, depending on whether the colon was preserved or not and whether the ileocecal valve was present (p>0.05).

Conclusion. An increase in citrulline level in the blood of children receiving therapy with a glucagon-like peptide-2 analog indicates the possibility of using this marker to monitor changes in intestinal absorption associated with physiological or pharmacological adaptation of the intestine.
A combined support vector regression with a firefly algorithm for prediction of energy consumption in wastewater treatment plants
Authors: Achite Mohammed , Samadianfard Saeed , Elshaboury Nehal , Toubal Kamel Abderezak , Abdelkader Eslam Mohammed , Sharafi Milad
Published: November 2024

Wastewater treatment plants (WWTPs) comprise energy-intensive processes, serving as primary contributors to overall WWTP costs. This research study proposes a novel approach that integrates support vector regression (SVR) with the firefly algorithm (FFA) for the prediction of energy consumption in a WWTP in Chlef City, Algeria. The database comprises a comprehensive set of 1,653 samples, capturing diverse information categories. It includes chemical and physical characteristics, encompassing chemical oxygen demand, 5-day biochemical oxygen demand, potential of hydrogen, water temperature, total suspended sediment in water and basin, influent N-NH3 concentration, number of aerators, and operating time. Additionally, the hydraulic and energy-related parameters are represented by the flow entered at the station and the energy consumed by aerators, respectively. Finally, meteorological data, comprising rainfall, temperature, relative humidity, and the aridity index, are part of the dataset required for analysis. In this regard, 15 different models that correspond to 15 different combinations of input parameters are assessed in this study. The results show that the SVR–FFA-15 can render an improvement in the prediction accuracy of energy consumption in WWTPs. This study provides a useful tool for managing the energy consumption of wastewater treatment and makes insightful recommendations for future energy savings.
"Such a Nasty Woman". Character Attacks in the 2016 U.S. Presidential Debates
Authors: Keohane Jennifer
Published: November 2024

This paper investigates Donald Trump’s character attacks on Hillary Clinton during the 2016 presidential debates. The most common character attacks that Trump used targeted Clinton’s anger and her judgment, attacks that I argue match the femininity/competence gendered double bind. I show how these attacks harmed Clinton’s credibility while building Trump’s.