bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of a six-month COVID-19 travel moratorium on Plasmodium falciparum malaria prevalence on Bioko Island, Equatorial Guinea
Authors: Hergott Dianna , Guerra Carlos , García Guillermo , Nzamio Jeremías , Donfack Olivier , Iyanga Marcos Mbulito , Nguema Restituto Mba , Abeso Crisantos Nsue , Mfumu Teresa Ayingono Ondo , Rivas Matilde Riloha , Phiri Wonder , Murphy Sean , Guthrie Brandon , Smith David , Balkus Jennifer
Published: April 2024

Importation of malaria infections has long been suspected as a driver of sustained malaria prevalence on areas of Bioko Island, Equatorial Guinea. However, quantifying the impact of imported infections is difficult because of the dynamic nature of the disease and the complexity of designing a randomized trial. Here, we leverage a six-month travel moratorium in and out of Bioko Island during the initial COVID-19 pandemic response to evaluate the contribution of imported infections to Pf prevalence on Bioko Island. Using a difference in differences design and data from island wide household surveys conducted before (2019) and after (2020) the travel moratorium, we compared the change in prevalence between areas of low historical travel to those with high historical travel. We found that prevalence increased in low travel areas after the moratorium compared to before, while prevalence decreased in high travel areas. In the absence of a travel moratorium, the prevalence of infection in high travel areas was expected to be 5% higher than what was observed. The observed decrease in prevalence can be directly attributed to the lack of imported cases, highlighting the importance of control measures that target these types of infections.
Artificial Intelligence and the Spatial Documentation of Languages
Authors: Ghanim Hakam
Published: April 2024

The advancement in technology has made interdisciplinary research more accessible. Particularly, the breakthrough in Artificial Intelligence (AI) has given huge advantages to researchers working in interdisciplinary and multidisciplinary fields. This study investigates the ability of AI models, particularly GPT-4 and GPT Data Analyst, in creating language maps for language documentation. The study Integrates documentary linguistics, linguistic geography, and AI by showcasing how AI models facilitate the spatial documentation of languages through the creation of language maps with minimal cartographic expertise. The study is conducted using a CSV file and a GeoJSON file both obtained from HDX and from the researcher’s fieldwork. The study data is then applied in real-time conversations with the AI models in order to generate the language distribution maps. The study highlights the two AI models capabilities in generating high-quality static and interactive web maps and streamlining the map-making process, despite facing challenges like inconsistencies and difficulties in adding legends. The findings suggest a promising future for AI in generating language maps and enhancing the work of documentary linguists as they collect their data in the field, pointing towards the need for further development to fully harness AI's potential in this field.
Unraveling Hypervirulent Klebsiella pneumoniae (hvkp): leveraging the Maga gene as a biomarker for strong biofilm forming hvkp
Authors: R Latha , Sasi Aravind , K Kavitha , sanjeevi Thiyagarajan , S Pramodhini , A Aboobacker P
Published: April 2024

Background
This study aims to distinguish hypervirulent Klebsiella pneumoniae (hvKp) from its classical counterpart (cKp) by utilizing Potassium tellurite agar (PTA) and the String test, with a focus on biofilm formation. The magA gene is investigated as a potential biomarker for identifying robust biofilm-producing hvKp strains, highlighting the significance of this research in addressing the global health threat posed by hvKp.
Methods
From January to December 2022, 102 Klebsiella pneumoniae isolates were collected from patients at AVMC&H, Puducherry. The identification of hvKp was performed using both phenotypic (PTA and the String test) and genotypic methods, including antimicrobial susceptibility testing and 96-well plate biofilm assays. The expression of hvKp-associated genes (rmpA, rmpA2, and magA) was assessed through conventional PCR.
Results
Phenotypic tests identified 28 isolates as hvKp via PTA and 23 through the String test. All rmpA-positive isolates were PTA positive, with 8 also positive in the String test. For rmpA2-positive isolates, 14 were positive in both tests. Fifteen isolates expressed the magA gene, with all showing positivity in the String test and 14 in PTA. Biofilm assays categorized isolates into non-biofilm producers (1.02%), moderate (36.73%), and strong biofilm producers (62.24%). Strong biofilm producers showed resistance to multiple antibiotics.
Conclusions
PTA and the String test are effective in identifying hvKp, with the magA gene serving as a promising biomarker for strong biofilm-producing isolates. The study reveals a concerning trend of antibiotic resistance among biofilm-producing isolates, indicating the potential for hvKp to evolve into a pan-drug-resistant superbug. This underscores the need for heightened global attention to mitigate the threats posed by hvKp.
Unraveling the therapeutic potential of Rutin against osteosarcoma cells: Targeting TNF-α and VEGF signaling pathways
Authors: Gnanamathy G. , Sheela S. Nancy , Jeevitha R. , Elumalai P. , Sri M.
Published: April 2024

Background
Rutin is a flavonoid that is widely distributed in plants and has been identified as having medicinal qualities as well as potential benefits for treating a range of ailments. In this work, we examined rutin's anticancer effects, specifically with regard to osteosarcoma, a type of bone cancer.
Methods and results
We evaluated the cytotoxic activity of rutin using MTT and LDH tests on the MG-63 osteosarcoma cell line, and the results showed a notable cytotoxic effect. Following rutin treatment, morphological alterations, such as membrane blebbing and cell shrinkage, were noted, which are typical of anticancer medications. Additionally, an in vitro assessment employing the wound healing assay revealed rutin's anti-migratory action on MG-63 cells. The results of the RT-PCR gene expression research pointed to possible pathways of rutin-induced apoptosis, including downregulation of the anti-apoptotic gene BCL-2 and elevation of pro-apoptotic genes including p53, Bax, and caspase-3. Additionally, the migration-causing genes VEGF and EGF were downregulated by rutin. Moreover, the relationship between rutin and proteins linked to osteosarcoma, like VEGF and TNF-α, was evaluated using in silico models.
Conclusion
The findings demonstrated effective binding at various binding sites, pointing to rutin's possible therapeutic use in the treatment of osteosarcoma. Although this work uses the MG-63 cell line to provide light on the anticancer activity of rutin against osteosarcoma, more preclinical research is necessary to establish the best dosages and assess safety profiles for the possible development of medications for the treatment of osteosarcoma.
Predominant determinants for Evaluation of Right Parasternal Approach in Transthoracic Echocardiography in Aortic Stenosis: A Study Based on Three-dimensional Cardiac Computed Tomography Analysis
Authors: Yokokawa Daisuke , Kuroki Yui , Mochizuki Yasuhide , Oda Ayaka , Gohbara Sakiko , Yamamoto Yumi , Ichikawa-Ogura Saaya , Hachiya Rumi , Toyosaki Eiji , Fukuoka Hiroto , Sunagawa Masataka , Shinke Toshiro
Published: April 2024

Purpose: The maximum blood flow velocity through the aortic valve (AVmax) using Doppler transthoracic echocardiography (TTE) is important in assessing the severity of aortic stenosis (AS). The right parasternal (RP) approach has been reported to be more useful than the apical approach, but the anatomical rationale has not been studied. We aimed to clarify the influence of the angle formed by the ascending aorta and left ventricle on Doppler analysis by TTE (Sep-Ao angle) and three-dimensional multidetector computed tomography (3D-MDCT) in patients with AS.
Methods: A total of 151 patients evaluated using the RP approach and 3D-MDCT were included in this study. The Sep-Ao angle determined using TTE was compared with that determined using 3D-MDCT analysis. In MDCT analysis, the left ventricular (LV) axis was measured in two ways and the calcification score was calculated simultaneously.
Results: The Sep-Ao angle on TTE was consistent with that measured using 3D-MDCT. In patients with an acute Sep-Ao angle, the Doppler angle in the apical approach was larger, potentially underestimating AVmax. Multivariate analysis revealed that an acute Sep-Ao angle, large Doppler angle in the apical approach, smaller Doppler angle in the RP approach, and low aortic valve calcification were independently associated with a higher AVmax in the RP approach than in the apical approach.
Conclusion: The Sep-Ao angle measured using TTE reflected the 3D anatomical angle. In addition to measurements using the RP approach, technical adjustments to minimize the Doppler angle to avoid bulky calcification should always be noted for accurate assessment.
The Acheulian site of Cantera Vieja (Madrid, Spain) and the Lower to Middle Palaeolithic transition in central Spain
Authors: Torres Concepción , Tapias Fernando , Demuro Martina , Arnold Lee J. , Arriolabengoa Martin , Díaz Sara , Baena Javier
Published: April 2024

The Cantera Vieja archaeological site is situated in Madrid, Spain, an area rich in Miocene flint and that has revealed several quarries at Lower and Middle Palaeolithic sites in recent years. Our study presents a multidisciplinary examination of the site, featuring an analysis of its geological context, site formation processes, chronological framework, and assemblage characteristics. Formed on the interfluvial platform between the Manzanares and Jarama Rivers, the Cantera Vieja site was created during the late Middle Pleistocene (194 ± 13 to 215 ± 16 ka) by alternating alluvial and mass-movement colluvial processes. The site boasts a typical Acheulian assemblage, characterized by numerous handaxes and preforms, and bifacial shaping flakes and fragments, with a limited number of flake supports, non-Levallois flaking elements, and a few final retouched tools. However, comparison of the archaeological assemblages across the Iberian Peninsula, including Cantera Vieja, with those reported from other contemporaneous sites across different parts of Europe indicates that this technocomplex could have slight location-specific differences in its industrial evolution. Our study at Cantera Vieja allows us to discuss the presence of specific lithic expression in the context of the western Acheulian in general and its transition to the Middle Palaeolithic in Iberia in particular. At the same time, the characteristics of the Cantera Vieja assemblage provide potentially generalizable insights into the social organization of lithic production during the late Middle Pleistocene. We consider that Cantera Vieja must have fulfilled an essential role as a place for training and learning biface knapping.
Based on in vivo and in vitro experiments validation: lncRNA MIR210HG inhibits esophageal squamous cell carcinoma and correlates with autophagy and apoptosis
Authors: Wang Jianyu , Zhang Zhenhu , Song Liang , Liu Xiangyan , He Xiaopeng
Published: April 2024

Background:Esophageal squamous cell carcinoma (ESCC) is a prevalent cancer that affects many people. The high death rate is still caused by ineffective early diagnostic and treatment methods. While the long non-coding RNA MIR210HG has been associated with several malignancies, its role in ESCC remains unclear. This study aims to explore the function of lncRNA MIR210HG in the pathogenesis of ESCC.Methods:We performed a pan-cancer analysis of lncRNA MIR210HG expression across various malignancies using the TCGA database, and we looked into the relationship between MIR210HG and the predictive survival of patients with ESCC. Moreover, we investigated MIR210HG's biological role using GO, KEGG, and GSEA enrichment analysis. In relation to MIR210HG, we also examined immune cell infiltration, immune checkpoint expression levels, tumor microenvironment (TME) features, and therapy sensitivity. To get more insight into the connection between lncRNA MIR210HG and ESCC, we assessed related gene and protein expression using Western blotting and RT-qPCR. To evaluate the proliferation, invasion, migration, apoptosis, and autophagy of ESCC cells, various techniques were employed, including EdU proliferation tests, wound healing assays, cell colony formation, transwell assays, flow cytometry, and an established xenograft mouse model.Results:lncRNA MIR210HG was found to be underexpressed in ESCC, and patients with higher expression levels of lncRNA MIR210HG exhibited increased survival rates. Overexpression of the lncRNA MIR210HG inhibited the proliferation, invasion, and migration of ESCC cells both in vitro and in vivo. Moreover, lncRNA MIR210HG was positively correlated with the P53 signaling pathway and influenced apoptosis and autophagy.Conclusion:In summary, lncRNA MIR210HG is a key gene affecting prognosis and immunity in ESCC and may influence apoptosis and autophagy through the P53 signaling pathway, offering new insights for the treatment of ESCC.
Assessing Measles Risk Transmission in Iran: A Utilization of the World Health Organization's Programmatic Risk Assessment Tool,2022
Authors: Dashti Elham , Karami Manoochehr , Zahraei Seyed Mohsen , Gharibnawaz Hassan , Sabouri Azam , Zavareh Fatemeh Azimian , Delpisheh Ali
Published: April 2024

Background
According to a study conducted in Iran, despite the country’s successful effort to eliminate measles, imported cases of the disease continue to be reported due to the endemic of measles in neighboring countries like Afghanistan and Pakistan. This research aims to evaluate the risk of measles transmission in different regions of Iran.
Methods
Utilizing data from the Measles case-based surveillance of the Expanded Program of Immunization spanning 31 provinces and 463 districts from 2019 to 2021, the research employed the WHO Measles Programmatic Risk Assessment tool. This tool evaluated the risk of disease transmission across four domains: population immunity, surveillance quality, program delivery performance, and threat assessment. The resulting scores were categorized as low, medium, high, or very high risk.
Results
During the years 2019–2021, the average incidence of measles was 1.9 per 1 million people، Sistan and Baluchestan had the highest provincial incidence rates (12.5 per one million population), Chabahar exhibited the highest district-level rates (76 per one million population). Conversely, Yazd and Mashhad demonstrated the lowest provincial (0.1 per one million population) and district-level (0.6 per one million population) incidence rates, respectively.
Conclusion
Although in the assessment of the risk of measles transmission at the provincial and district levels, all regions were placed at a low level of the risk of disease transmission, this tool is not able to assess the risk at the level of the rural sector or peripheral sectors such as comprehensive health service centers. Therefore, the evaluation of the risk of measles disease transmission for low levels can have more than one weakness. Emphasize the strength of the surveillance and immunization system of the country. The indicators used in this tool are the same for all countries with different epidemiological features (elimination, endemic). Sensitivity analysis can optimize the use of this tool for countries with different disease conditions.
Exploring the prevalence of anxiety, obsessive-compulsive, and major depressive disorders in men with concurrent substance use
Authors: Nia Mostafa Abdollahi , Saeidi Mahdieh , Ghalichi Leila , Ahmadkhaniha Hamidreza
Published: April 2024

Purpose
Assessing the co-occurrence of psychiatric disorders alongside substance use disorder is crucial for comprehensive treatment. This study aimed to explore the prevalence of generalized anxiety, obsessive-compulsive, and major depressive disorders among men engaging in concurrent use of multiple substances.
Methods
This descriptive study involved selecting 220 patients aged between 18 and 60 years who were referred to Iran Psychiatric Hospital for treatment during 2022 and 2023. The study determined the prevalence of generalized anxiety, obsessive-compulsive, and major depressive disorders among the patients. Statistical analysis was conducted using SPSS software, employing T-tests and Chi-Square tests.
Results
The average age of the participants was 37.10 ± 9.62 years. Findings revealed that the most prevalent substance use disorders among patients were cannabis (19.1%), clonazepam (13.4%), methamphetamine (12.9%), and opium (12.2%) (P < 0.0001). The prevalence of major depression, generalized anxiety, and obsessive-compulsive disorders among patients was estimated at 39.7% ± 6.5%, 32.6% ± 6.3%, and 33.9% ± 6.3%, respectively, with no significant difference in their occurrence (P = 0.402). Overall, the prevalence of mental disorders was found to be 74.6% ± 5.8%, with 46.9% of patients experiencing one mental disorder, 23.7% experiencing two, and 4% experiencing all three. Additionally, an inverse relationship between education level and the prevalence of psychiatric disorders was observed (P < 0.05).
Conclusion
Generalized anxiety, obsessive-compulsive, and major depressive disorders are highly prevalent among men engaging in concurrent use of multiple substances. This underscores the need for simultaneous intervention for both substance abuse and psychiatric disorders. Adopting the Iceberg metaphor encourages a deeper exploration, fostering optimism for more effective solutions in addressing these complex interrelated issues.
Examining patterns in rainfall and temperature data within the Malaprabha Right Bank Canal Command Area (MRBC) using statistical techniques such as the Mann-Kendall test and Sen's Slope Estimator
Authors: Srini Madhusudhan Mandya , Shivapur Anand V , J Surendra H
Published: April 2024

Examining the presence of climate change through trend analysis of rainfall and temperature variables has gained recognition due to their significant implications. The pressing global issue of escalating temperatures coupled with unpredictable, diminishing rainfall is particularly critical, especially in regions heavily reliant on rain-fed agriculture. This study focuses on the Malaprabha Canal Command Area (MRBC) and aims to assess dynamic changes in meteorological variables, offering valuable insights for effective adaptation strategies. The investigation spans a comprehensive analysis of long-term climatic data, specifically a 30-year period from 1991 to 2020. Rainfall trends across six stations within the entire Malaprabha right bank canal command area are explored on a monthly, seasonal, and annual basis. Additionally, the study scrutinizes maximum and minimum temperature trends from 2000 to 2019 at seven selected stations in and around MRBC. The analytical approach involves the application of the Mann-Kendall test and Sen’s slope estimates, maintaining a significance level of 5%. Results from the detailed trend analysis of MRBC indicate the absence of a significant trend at the 95% confidence level in the region. However, the study identifies both increasing and decreasing trends in annual rainfall at selected stations. Furthermore, no significant trend emerges in the temperature data for annual series throughout MRBC. Notably, a significant negative trend is observed during pre-monsoon and post-monsoon periods, while a significant positive trend is identified at the Ron station. These findings contribute valuable information for understanding the climatic dynamics in MRBC and serve as a basis for formulating informed strategies to address climate-induced challenges.
Reliability and Validity of the Chinese Version of the Contraceptive Knowledge Assessment Scale in College Students
Authors: Zhang Jiayang , Tian Maoting , Xu Lei
Published: April 2024

Objectives: To translate and revise the Contraceptive Knowledge Assessment (CKA) scale and apply it to college students. After cross-cultural debugging of the source scale, the reliability and validity of the Chinese version of the scale were tested.
Study design: Based on the principle of scale introduction, the contraceptive knowledge assessment scale was translated and back-translated, and cross-cultural adjustment and revision were carried out. A survey was then conducted among 388 college students in Shanghai to test the reliability and validity of the Chinese version of the CKA scale.
Results: There were 22 items in the Chinese version. Factor analysis extracted 8 common factors, with a cumulative contribution rate of 58.923%. The Cronbach's α coefficient was 0.793, and the test-retest reliability Pearson correlation coefficient was 0.743.
Conclusion: The Chinese version of the CKA scale has good reliability and validity and is suitable for assessing the level of contraceptive knowledge.
Evaluation of the intramammary distribution of breast lesions detected by MRI but not conventional second- look B-mode ultrasound using an MRI/ultrasound fusion technique
Authors: Saito Masayuki , Banno Hirona , Ito Yukie , Ido Mirai , Goto Manami , Ando Takahito , Mouri Yukako , Kousaka Junko , Fujii Kimihito , Imai Tsuneo , Nakano Shogo , Suzuki Kojiro
Published: April 2024

The objective of this study was to evaluate the intramammary distribution of MRI-detected mass and focus lesions that were difficult to identify with conventional B-mode ultrasound (US) alone. Consecutive patients with lesions detected with MRI but not second-look conventional B-mode US were enrolled between May 2015 and June 2023. Following an additional supine MRI examination, we performed second-look US using real-time virtual sonography (RVS), an MRI/US image fusion technique. We divided the distribution of MRI-detected mammary gland lesions as follows: center of the mammary gland versus other (superficial fascia, deep fascia, and atrophic mammary gland). We were able to detect 27 (84%) of 32 MRI-detected lesions using second-look US with RVS. Of these 27 lesions, 5 (19%) were in the center of the mammary gland and 22 (81%) were located in other areas. We were able to biopsy all 27 lesions; 8 (30%) were malignant and 19 (70%) were benign. Histopathologically, three malignant lesions were invasive ductal carcinoma (IDC; luminal A), one was IDC (luminal B), and four were ductal carcinoma in situ (low-grade). Malignant lesions were found in all areas, with no statistical differences in frequency between the center of the mammary gland and other areas (p = 0.601). In this study, 81% of the lesions identified using second-look US with RVS were located outside the center of the mammary gland. Thus, we consider it important to carefully examine other areas for breast lesions when performing second-look US when a lesion has been detected with MRI but not with second-look conventional B-mode US.
Impact of systemic steroids on the efficacy of first line imatinib treatment of patients with advanced gastrointestinal stromal tumors (GISTs)
Authors: Kim Sejin , Kim Hyung-Don , Kim Eo Jin , Ryu Min-Hee , Kang Yoon-Koo
Published: April 2024

Background: Effective management of adverse events is required to maintain sufficient imatinib dosing when treating patients with gastrointestinal stromal tumors (GISTs). Skin rash is a common adverse event of imatinib, which can be effectively controlled by systemic steroid treatment without imatinib dose modification or interruption. However, the impact of the use of systemic steroids on the efficacy of imatinib treatment remains unclear.
Methods: Between October 2014 and February 2022, 277 consecutive patients from a prospective registry of GIST patients were included as the study population. Patients who started systemic steroids due to grade ≥ 3 skin rash or grade 2 skin rash with grade 2 pruritis were classified as the steroid group, whereas patients who did not develop a skin rash or those who did not require steroids for a mild skin rash were classified as the control group. Efficacy outcomes were compared between the two groups.
Results: Among the 277 patients, 30 (10.8%) were treated with systemic steroids for skin rash. There was no significant difference in PFS or OS between the steroid and control groups (3-year PFS, 67.7% vs. 65.1%, p=0.53; 3-year OS, 91% vs. 89.9%, p=0.67, respectively). The use of systemic steroids was not an independent factor associated with PFS (HR 0.87, 95% CI 0.46–1.65, p=0.664) and OS (HR 0.53, 95% CI 0.19–1.46, p=0.218). In the steroid group, patients who successfully maintained the imatinib dosage showed a trend toward more favorable survival outcomes than those who did not (3-year PFS, 73.3% vs. 44.4%, p=0.34; 3-year OS, 95.8% vs. 75.0%, p=0.15, respectively).
Conclusions: The use of systemic steroids for the control of imatinib induced severe skin rash did not adversely affect the efficacy outcomes of imatinib in patients with advanced GIST.
Improving the Spectral Resolution and Wavelength Scale of Solar Flares Using SDO/EVE MEGS-A Level 0B Image Data
Authors: Gonzalez Gabriela , Chamberlin Phillip , Herde Vicki
Published: April 2024

The EUV Variability Experiment (EVE) is one of three instruments onboard the Solar Dynamics Observatory (SDO). This paper focuses on using the ”A” channel on the Multiple EUV Grating Spectrographs (MEGS-A) on EVE, which measures wavelengths of 5-37nm, to improve the wavelength scale accuracy and spectral resolution during solar flares. In this study, an X2.2 class flare that occurred on 15 February 2011, SOL2011-02-15T0156, was used to derive pixel-to-wavelength scales. EVE’s Level 0B data product is used to create updated wavelength scales that are shown, through this analysis, to make more precise spectral measurements compared to EVE Level 2 data. An X2.2 class flare that occurred on 15 February 2011, SOL2011-02-15T0156, was used to derive the pixel-to-wavelength scales. An improvement range of 5.21% to 11.35% was found in the emission line widths. In the future, these measurements can be used for improved Doppler velocity calculations of the accelerated plasma of various temperatures during solar flares.
The metabolic and physiological responses to spaceflight of a lipopeptide- producing Bacillus subtilis
Authors: Qin Wan-Qi , Liu Yi-Fan , Liu Jin-Feng , Zhou Lei , Yang Shi-Zhong , Gu Ji-Dong , Mu Bo-Zhong
Published: April 2024

Background
The outer space is an extreme environment that has attracted continuous interest in microbial adaptation and safety, due to its high mutagenesis frequency and genetic variability. To date, several studies have assessed the impact of the space environment on the microbiomes and microorganisms. While the survival of Bacillus subtilis after spaceflight is well established, how the phenotype and metabolic function of B. subtilis respond to space stress is rarely reported.
Results
In this study, we performed a space flight of the B. subtilis TD7 strain facilitated by the launch project of the Xinyidai Zairen Feichuan-Shiyan Chuan, and compared the strains after spaceflight with the wild-type in terms of their growth, morphology, biofilm formation and secondary metabolism. The spaceflight strain exhibited slower growth, higher cell density, different morphology and decreased biofilm formation. Importantly, a decrease in the lipopeptide production was observed after spaceflight. Thus, we used a multi-omics approach to uncover the molecular mechanisms underlying the changeable secondary metabolism. A total of 14 gene clusters for secondary metabolite biosynthesis were identified in both the wild-type strain and spaceflight strains through whole-genome sequencing, including nonribosomal peptide synthetase. The comparative transcriptome revealed 997 differentially expressed genes which involved in the TCA cycle, fatty acid degradation, amino acid biosynthesis, and quorum sensing systems. The differential expression analysis of 26 lipopeptide-related DEGs further elucidated the relationship between the space environment and the regulation of secondary metabolism.
Conclusion
Our study is the first study to provide new insight into the behaviors, metabolic functions and adaptation mechanisms of B. subtilis in response to spaceflight. This knowledge could contribute to a better understanding of the relationship between the space environment and microbial adaption mechanisms.
Predictors of continuation for asenapine from real-world data in patients with schizophrenia
Authors: Takekita Yoshiteru , Hiraoka Shuichi , Iwama Yasuhiro , Matsui Daisuke , Aoki Nobuatsu , Ogata Haruhiko , Funatsuki Toshiya , Shimizu Toshiyuki , Murase Yuji , Shimamoto Yutaro , Koshikawa Yosuke , Kato Masaki
Published: April 2024

Background
The continuation rates of pharmacotherapy in schizophrenia exhibit variability, a phenomenon influenced by the specific antipsychotic agent prescribed and patient-related factors such as age and duration of illness. In this context, our study aims to elucidate the predictors of medication continuation for asenapine sublingual tablets, characterized by unique formulation properties.
Methods
Our investigation leveraged real-world data collected through post-marketing surveillance in Japan, comprising 3,236 cases. Utilizing multivariate logistic regression analysis, we identified patient-related factors associated with medication continuation as the primary outcome measure, subsequently employing survival analysis for further evaluation. Additionally, adverse event occurrence was assessed as a secondary outcome measure.
Results
Multivariate logistic regression analysis unveiled significant predictors of asenapine continuation, notably including patient-related factors such as a chlorpromazine equivalent dose exceeding 600 mg/day and an illness duration of 25 years or more. While the overall continuation rate stood at 40.6%, patients exhibiting factors such as a chlorpromazine equivalent dose surpassing 600 mg/day or an illness duration exceeding 25 years demonstrated continuation rates of 46.3% and 47.9%, respectively. Remarkably, patients presenting both factors showcased the highest continuation rate at 52.5%.
Conclusions
Our findings shed light on distinct patient-related predictors of asenapine continuation, deviating from those observed with other antipsychotic medications. This underscores the necessity of recognizing that predictive factors for antipsychotic medication continuation vary across different agents. Moving forward, elucidating these predictive factors for various antipsychotic medications holds paramount importance in schizophrenia treatment, facilitating the delivery of tailored therapeutic interventions for individual patients.
Study on the impact of coordinated development of two-way FDI on energy performance
Authors: Wang Fei , Zhang Wei , Jing Man , Ye Linwei
Published: April 2024

With the continuous expansion of the scale of two-way FDI, it not only plays an important role in China's economy, but also profoundly affects the regional environment. Therefore, based on data from 30 provinces and regions in China from 2003 to 2019, this article calculates the coordinated development level of bidirectional FDI, and uses the construction of NDDF non radial directional distance function to measure energy performance, studying the relationship between coordinated development of bidirectional FDI and energy performance. Research has found that continuously improving the coordinated development level of two-way FDI can significantly improve the energy performance index, thereby suppressing environmental pollution and promoting regional sustainable development. Bidirectional FDI has a positive regulatory effect on energy performance through two paths: research and development investment and promoting industrial upgrading. The energy-saving and emission reduction effects of bidirectional FDI have regional heterogeneity, and are more significant in the eastern and central regions than in the western regions, while the effect in the northern regions is more significant than in the southern regions. Therefore, adjusting measures to local conditions to improve the scale and quality of two-way FDI, continuously improving the coordinated development level of two-way FDI, plays an important role in achieving the "dual carbon" goal.
Chronic exposure to polycyclic aromatic hydrocarbons is associated with alterations in skin virome composition and increased virus–host coevolution
Authors: Du Shicong , Tong Xinzhao , Leung Marcus H. Y. , Betts Richard J. , Woo Anthony C. , Bastien Philippe , Misra Namita , Aguilar Luc , Clavaud Cécile , Lee Patrick K. H.
Published: April 2024

Background: Viruses play an essential role in the human skin microbiome under healthy and diseased conditions. We previously reported that exposure to polycyclic aromatic hydrocarbons (PAHs) led to the differentiation of bacteria samples from the cheeks of 124 Chinese women into two cutotypes with distinct taxonomic and functional compositions. In addition, we found that women with a high level of PAH exposure exhibited skin dryness and hyperpigmentation. However, the characteristics of viruses associated with these cutotypes are not well understood. In this study, we employed bulk metagenomic sequencing to investigate the diversity and functions of skin viromes and the virus–host interactions of the two cutotypes.
Results: The viruses associated with the two cutotypes had distinct diversities, compositions, functions, and lifestyles. Moreover, virus–host interactions were substantially increased by high levels of PAH exposure, especially when the hosts were potential pathogens. Under high- PAH exposure conditions, the viruses were enriched in xenobiotic degradation functions, and there was evidence suggesting that the insertion of bacteriophage-encoded auxiliary metabolic genes into hosts aids biodegradation. Furthermore, under low-PAH exposure conditions, virus– host interactions followed the “Piggyback-the-Winner” model, with Cutibacterium strains being “winners,” whereas under high-PAH exposure conditions, the interactions followed the “Piggyback-the-Persistent” model, with the biodegradation bacteria being “persistent.”
Conclusion: Our findings demonstrate that PAHs not only influence skin bacteria but also impact the composition of skin viruses and their interactions with skin bacteria, which may influence skin health. A detailed understanding of the roles played by viruses on skin exposed to air pollutants would aid the development of strategies to harness the potential of viruses to prevent undesirable skin conditions.
APG-1252 combined with Cabozantinib inhibits hepatocellular carcinoma through MEK/ERK and CREB/Bcl-xl pathways
Authors: Di Tian , Luo qiuyun , Song Jiang-tao , Yan Xiang-lei , Zhang Lin , Pan Wen-tao , Guo Yu , Lu Fei-teng , Sun Yu-ting , Xia Zeng-fei , Yang Li-qiong , qiu miao-zhen , yang da-jun , sun jian
Published: April 2024

Background and Purpose
Liver cancer is the fourth leading cause of cancer-related death worldwide, and hepatocellular carcinoma (HCC) is the most common primary liver cancer. APG-1252 is a small molecule inhibitor of Bcl-2/Bcl-xl, and the anti-tumor effect of APG-1252 in HCC, or its anti-tumor effects in combination with cabozantinib, has not been researched.
Experimental Approach:
TCGA database analysis was used to analysis the gene expression levels of Bcl-2 and Bcl-xl in HCC tissues. Western Blot was used to detect the proteins’ expression level. And the inhibitory effects of APG-1252 and Cabozantinib on the proliferation of HCC cell lines was detected by CCK-8. The effect on the migration and invasion of HCC cells was verified by Transwell assay. Huh7 xenograft model in nude mice was used to detect the combined effect in vivo.
Key Results:
We found that APG-1252 monotherapy could inhibit the proliferation and migration of HCC cells and promote apoptosis of HCC cells. APG-1252 combined with Cabozantinib could inhibit the proliferation, migration and invasion of HCC cells and promote the apoptosis of hepatocellular carcinoma cells and exerted synergistic effect in vivo. The combination could significantly downregulate MEK/ERK phosphorylation levels. Besides, the treatment of Cabozantinib could cause the protein level of phosphorylation CREB and BCL-XL increased, while combined with APG-1252 could impair this effect.
Conclusion and Implications:
Our data suggest that APG-1252 in combination with Cabozantinib can provide more effective treatment strategies for HCC patients and deserve further clinical investigation.
Unveiling Molecular Moieties through Hierarchical Graph Explainability
Authors: Sortino Paolo , Contino Salvatore , Perricone Ugo , Pirrone Roberto
Published: April 2024

Background: Graph Neural Networks (GNN) have emerged in very recent years as a powerful tool for supporting in silico Virtual Screening. In this work we present a GNN which uses Graph Convolutional (GC) architectures to achieve very accurate multi-target screening. As novelty compared to state-of-the-art we devised a hierarchical Explainable Artificial Intelligence (XAI) technique to catch information directly at atom, ring, and whole molecule level by leveraging the message passing mechanism. In this way, we find the most relevant moieties involved in bioactivity prediction.
Results: We report a state-of-the-art GNN classifier on twenty Cyclin-dependent Kinase targets in support of VS. Our classifier outperforms previous SOTA approaches proposed by the authors. Moreover, a CDK1-only high-sensitivity version of the GNN has been designed to use our explainer in order to avoid the inherent bias of multi-class models. The hierarchical explainer has been validated by comparison with literature, experimental and docking data on 19 approved drugs on CDK1. Our explainer provided information in accordance to the docking analysis for 17 out of the 19 test drugs.
Conclusion: Our approach is a valid support for shortening both the screening and the hit-to-lead phase. Detailed knowledge about the molecular substructures that play a role in the inhibitory action, can help the computational chemist to gain insights into the pharmacophoric function of the molecule also for repurposing tasks.
Tea Grading and Counting Recognition Model Based on YOLOv8n-SSMC
Authors: Xia Yuxin , Wang Zejun , Cao Zhiyong , Chen Yaping , Li Limei , Chen Lijiao , Zhang Shihao , Li Hongxu , Wang Chun , Wang Baijuan
Published: April 2024

In order to solve the problems of dense distribution, limited feature extraction ability, and false detection in the field of tea grading recognition, a YOLOv8n-SSMC tea grading and counting recognition model was proposed in this study. Firstly, the SPD-Conv module was embedded into the backbone of the network model to enhance the deep feature extraction ability of the target. Secondly, the Super-Token Vision Transformer was integrated to reduce the attention of the model to redundant information, thus improving the perception ability of tea. Subsequently, the positioning loss function was improved to MPDIoU, which accelerated the convergence speed of the model, optimized the performance of the model. Finally, the classification positioning counting function was added to achieve the purpose of classification counting. The experimental results showed that the precision, recall and average precision improved by 17.6%, 19.3%, and 18.7% respectively. The average precision of single bud, one bud and one leaf, and one bud and two leaves were 88.5%, 89.5% and 89.1% respectively. In this study, the YOLOv8n-SSMC recognition model demonstrated strong robustness and proved suitable for tea grading edge picking equipment, laying a solid foundation for the realization of mechanized tea industry.
Dexmedetomidine promotes NREM sleep by depressing the neuronal activity of OXT neurons in the PVN
Authors: Zhang Ying , Li Jiaxin , Wang Wei , Wang Daming , Ding Junli , Wang Liecheng , Cheng Juan
Published: April 2024

This study aimed to investigate the mechanism of Dexmedetomidine (DEX) on sleep homeostasis. We will focus on the effect of DEX on the activity and the signal transmission of oxytocin-expressing (Oxytocin, OXT) neurons in the paraventricular nucleus (PVN) of the hypothalamus (PVNOXT) in the regulation of sleep-wakefulness cycle. In this study, the guide cannula was implanted to microinject DEX into PVN. PVNOXT neurons were specifically activated by the chemogenetic method. Differences in sleep-wakefulness states were monitored by electroencephalogram (EEG)/ electromyogram (EMG) recording. In addition, the effect of DEX on the electrophysiological activity of PVNOXT neurons was examined by whole-cell patch-clamp technique. EEG/EMG results showed that microinjection of DEX in PVN significantly increased the duration of nonrapid eye movement (NREM) sleep in mice. Chemogenetic activation of PVNOXT neurons after internal cannula injection of DEX to PVN increased the amount of wake. Electrophysiological results show that DEX could inhibit the frequency of action potential (AP) and the spontaneous excitatory postsynaptic current (sEPSC) in PVNOXT neurons through α2-adrenoceptors. DEX maintained sleep homeostasis by inhibiting excitatory synaptic signaling in PVNOXT neurons through α2-adrenoceptors.
Investigating the correlation between PD-L1 expression and radiomics predictions in non-small cell lung cancer using PET/CT imaging analysis
Authors: chang Ruxi , Shen Cong , Luo Liang , Liu xiang , Li Yan , Duan Xiaoyi
Published: April 2024

Background
This study aims to build a clinical factor model by incorporating clinical factors and metabolic parameters, as well as lesion imaging features from PET/CT images. Additionally, radiomics models are established based on PET-CT images to assess its capability in predicting PD-L1 expression in patients with non-small cell lung cancer.
Methods
After retrospective data collection, based on the clinical factor logistic regression results, a clinical factor model was constructed. The regions of interest (ROIs) for PET in radiomics were delineated using a semi-automatic method, while those for diagnosis CT were manually delineated. After extracting radiomic features, feature selection was performed using variance analysis, correlation analysis, and Gradient Boosting Decision Tree (GBDT). PET, diagnosis CT, and combined models were constructed. Predictive power was evaluated through ROC analysis comparing different models.
Result
In all 104 cases(mean age, 63.90years+/-8.99, 62males) were evaluated. The SUVmax in the PD-L1 positive group was higher than that in the negative group (P = 0.04), but both metabolic parameters and imaging features showed no correlation with PD-L1 expression. The radiomics models outperformed the clinical factor model (AUC = 0.712), yet the clinical factor model exhibited higher specificity than all radiomics models (Specificity = 0.765). The predictive performance of the PET model surpassed that of the diagnosis CT model (AUC: 0.838 vs 0.723). The combined model demonstrated enhanced predictive performance (AUC = 0.874).
Conclusion
The radiomics models perform better in predicting PD-L1 expression than the clinical factor model. The radiomics model combining PET and diagnosis CT exhibits the best predictive performance.
Adam19 Deficiency Impacts Pulmonary Function: Human GWAS Follow-up in Mouse
Authors: Li Huiling , House John , Nichols Cody , Gruzdev Artiom , Ward James , Li Jian-Liang , Wyss Annah , Haque Ezazul , Edin Matthew , Elmore Susan , Mahler Beth , Degraff Laura , Shi Min , Zeldin Darryl , London Stephanie
Published: April 2024

Purpose
Over 550 loci have been associated with human pulmonary function in genome-wide association studies (GWAS); however, the causal role of most remains uncertain. Single nucleotide polymorphisms in a disintegrin and metalloprotease domain 19 (ADAM19) are consistently related to pulmonary function in GWAS. Thus, we used a mouse model to investigate the causal link between Adam19 and pulmonary function.
Methods
We created an Adam19 knockout (KO) mouse model and validated the gene targeting using RNA-Seq and RT-qPCR. Contrary to prior publications, the KO was not neonatal lethal. Thus, we phenotyped the Adam19 KO.
Results
KO mice had lower body weight and shorter tibial length than wild type (WT). Dual-energy X-ray Absorptiometry indicated lower soft weight, fat weight, and bone mineral content in KO mice. In lung function analyses using flexiVent, compared to WT, Adam19 KO had decreased baseline respiratory system elastance, minute work of breathing, tissue damping, tissue elastance, and forced expiratory flow at 50% forced vital capacity but higher FEV0.1 and FVC. Adam19 KO had attenuated tissue damping and tissue elastance in response to methacholine following LPS exposure. Adam19 KO also exhibited attenuated neutrophil extravasation into the airway after LPS administration compared to WT. RNA-Seq analysis of KO and WT lungs identified several differentially expressed genes (Cd300lg, Kpna2, and Pttg1) implicated in lung biology and pathogenesis. Gene set enrichment analysis identified negative enrichment for TNF pathways.
Conclusion
Our murine findings support a causal role of ADAM19, implicated in human GWAS, in regulating pulmonary function.
Assessing the Clinical Implications of Ischemic Preconditioning through CAIX Expression in Rectal Cancer Patients.
Authors: FRANDON Julien , CHAVEROUX Cedric , LAVAL Pierre-Alexandre , GABARROU Gabrielle , FERRARO-PEYRET Carole , BERTRAND Martin M
Published: April 2024

Background:
Anastomotic leak is a significant concern following rectal cancer surgery, often attributed to ischemic events during surgery. Preoperative ischemic conditioning through embolization of the inferior mesenteric artery may improve colonic perfusion. However, the cellular mechanisms underlying this ischemic preconditioning remain unclear.
Methods:
This ancillary study aimed to explore the cellular correlation of ischemic preconditioning through carbonic anhydrase IX (CAIX) expression in patients undergoing rectal cancer surgery. Normal colonic tissues from ten patients, five with ischemic preconditioning and five controls, were stained against CAIX. The number of intestinal crypts exhibiting CAIX fixation was quantified and compared between the two groups. The resistive index (RI) at the time of surgery and the complications during the 2-year follow-up were also reported.
Results:
Patients who underwent ischemic preconditioning demonstrated a significantly smaller decrease in RI values (p = .03) and less pronounced CAIX fixation compared to controls, although without statistical significance (p = 0.42). CAIX staining was significantly lower in patients without a significant decrease in RI (p = 0.04). Patients with a significant decrease in RI and marked increase in CAIX exhibited a higher rate of complications and lower rate of digestive continuity restoration.
Conclusion:
This study suggests a potential correlation between CAIX expression and RI drop in patients undergoing rectal cancer surgery, indicating a role for CAIX as a cellular marker of ischemic preconditioning. Ischemic preconditioning by early embolization may reduce CAIX expression, suggesting a protective effect on ischemic tissue.
Clinical trial: NCT03628248, 2021-08-04