bluuebunny/crossref_metadata_2025 huggingface dataset:
A Call To Action: Black Male Educators! It is Your Time: A Mixed Methods Study on Beginning Black Male Educator’s Experiences in Teacher Preparation Programs, Preparedness, and Opportunities for Retention
Authors: Jackson Leonard , Dicks Towan
Published: June 2024

The purpose of this sequential explanatory mixed method study was to understand the beginning Black male teachers’ (BMT) preparedness, perceptions of the pre-service experience, and give opportunities for retention for Teacher Education Programs. The significance of this study was to fill the significant void in research, understand the preparedness of African American male students through a teacher preparation program, and to understand the beginning teachers' preparedness and the ability to fully execute their roles as a classroom teacher. This study used a sequential explanatory mixed method design which included survey collection and in-depth interviews to explore the critical lived experiences of the participants. The quantitative data was collected from 104 Black Male Educators. The data content validity was checked with the Pearson r 2-tailed correlation. Qualitative data was collected from the interviews of five (5) beginning Black Male Educators. The researcher interpreted the statements from the interviews and conducted an analysis revealing codes and themes. Four major themes emerged from the data, which were: (1) Self-Efficacy, (2) Teacher Preparation Programs are effective, (3) Family Dynamics and Socioeconomics play a critical role, and (4) Representation of Black Men Matters. The conclusions specified that Teacher Preparation Programs are effective in the trajectory of Black male educators. However, the findings revealed that the further Black male educators move away, in time, from their programs, the less they it as a factor in their effectiveness. The findings revealed that there was a significant relationship between the beginning African American male educator and their preparedness by their Teacher Preparation Program. The findings additionally show that the further the beginning Black Male Educator moves away from their program, the least impact it has on their level of preparedness to fulfill their role. The study revealed several recommendations for practice and research that would improve the lived experiences of Black male educators including mentorships in Teacher Preparation Programs, Partnerships amongst Teacher Preparation Programs and School districts, and Empowerment and Continual Support of Black Male Educators. The participants responses provide a framework for Teacher Preparation Program stakeholders, current administrators, and district-level staff recruiters to follow.
Artificial intelligence-based morphologic classification and molecular characterization of neuroblastic tumors from digital histopathology
Authors: Applebaum Mark , Ramesh Siddhi , Dyer Emma , Pomaville Monica , Doytcheva Kristina , Dolezal James , Kochanny Sara , Terhaar Rachel , Mehrhoff Casey , Patel Kritika , Brewer Jacob , Kusswurm Benjamin , Naranjo Arlene , Shimada Hiroyuki , Sokol Elizabeth , Cohn Susan , George Rani , Pearson Alexander
Published: June 2024

A deep learning model using attention-based multiple instance learning (aMIL) and self-supervised learning (SSL) was developed to perform pathologic classification of neuroblastic tumors and assess MYCN-amplification status using H&E-stained whole slide digital images. The model demonstrated strong performance in identifying diagnostic category, grade, mitosis-karyorrhexis index (MKI), and MYCN-amplification on an external test dataset. This AI-based approach establishes a valuable tool for automating diagnosis and precise classification of neuroblastoma tumors.
Optimization of DMAs design and cooperative pressure reducing valves and pumping stations to achieve leakage control and energy saving strategy of water distribution networks
Authors: Li HongYan , Shi Wentao , Chang Zifeng , Zhang Feng , Cui Jianguo , Lu Xulong , Mao Libo
Published: June 2024

Leakage and energy consumption in urban water distribution networks (WDNs) have been receiving increasing attention, and pressure management based on district metered areas (DMAs) can effectively control leakage and save energy. In this paper, a new design method for establishing DMAs and carrying out pressure management is proposed. First, the combination of the non-dominated sorting genetic algorithm (NSGA-III) and spectral clustering algorithms, considering the partition cost, operation and management difficulty, post-partition water quality safety, and network water supply capacity factors, identifies the best DMA layouts and the corresponding boundary pipes with the help of multicriteria decision making (MCDM) methods. Second, the non-dominated sorting genetic algorithm (NSGA-II) is used to solve the optimal arrangement model of valves and flow meters on the boundary pipes, and the optimal arrangement is determined based on the equipment cost, water quality safety, and leakage control effect after partition. Finally, pressure reducing valves (PRVs) are installed at the inlet of the DMAs, and a genetic algorithm is used to solve the joint scheduling optimization model of the PRVs and pump station in WDNs to determine the optimal scheduling strategy for the PRVs and the fixed and variable speed pumps for leakage control and energy saving. The proposed method is applied to the SH town network. Results reveal that the method can establish DMAs considering multiple objectives. Furthermore, pressure management in DMAs can not only significantly reduce leakage and energy consumption of pumping stations but also improve the water quality of networks. Therefore, this method can provide a reference for water utilities in establishing DMAs and carrying out pressure management in WDNs in the future.
Psychological Difficulties and the Needs for Counseling Services in High School Students
Authors: Le Cong Minh , Huynh Son-Van , Nguyen Vu Hoang Anh , Le Vy Truc , Luu-Thi Huyen-Trang , Tran-Chi Vinh-Long
Published: June 2024

Adolescents experience numerous changes, both psychologically and physically, and they are also the age group with a high prevalence of mental problems that need counseling help. The study aims to assess the demand for psychological services among adolescents, a vital concern that must be discussed. A total of 672 high school students were collected in Thu Duc City, Vietnam. The results showed that there was a statistically significant difference between grades 10–12 in student’s difficulties (DS), need for psychological support (NPS), and request for psychology services (RPS). Additionally, there was a statistically significant difference in student performance for DS. The findings also implied that RPS was predicted by a DS, NPS, and factors affecting the need to use psychological services (FA), in which NPS and DS were mediators in the relationship between FA and RPS. The study significantly contributes to research practices and the theoretical framework that the parliament and the government use to make counselors mandatory in schools. Meanwhile, the study suggested that school counselors, educators, and teachers must appropriately evaluate students' counseling needs and psychological difficulties; this is essential to providing support and interventions when students deal with challenges promptly.
Reduced muscle mass is an important part of Global Leadership Initiative on Malnutrition criteria in nutritional diagnosis of hepatocellular carcinoma
Authors: Li Juan , Jiang Minjie , Hua Xin , Xu Hongxia , Wu Muchen , Wu Jing , Liu Songtao , Shi Hanping , Meng Qinghua
Published: June 2024

Background
The Global Leadership Initiative on Malnutrition criteria (GLIM) was established to build a global consensus on the diagnostic criteria for malnutrition. The study aimed to assess the prevalence of the malnutrition diagnosed by GLIM criteria for patients with hepatocellular carcinoma (HCC), and to determine the role of the reduced muscle mass defined by CT scans in the GLIM criteria.
Methods
This cohort research was conducted on adult patients with HCC. The risk of malnutrition was screened by Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. The third lumbar vertebrae (L3-SMI) were used to represent the muscle mass in GLIM criteria. The variables associated with overall mortality were assessed by multivariate Cox regression analyses.
Results
The prevalence of malnutrition defined by GLIM criteria was 49.7% (179/360) in patients with HCC. If reduced muscle mass was not included in GLIM criteria, the prevalence of malnutrition was 31.7% (114/360). GLIM-defined malnutrition (HR=1.979, 95%CI 1.019-3.841, P=0.044) was independently associated with overall mortality in patients with HCC. However, the GLIM-defined malnutrition (without muscle mass) was not associated with overall mortality (HR=0.863, 95%CI 0.399-1.867, P=0.709).
Conclusions
Skeletal muscle mass is an important part of GLIM criteria in patients with HCC. The malnutrition is common in patients with HCC, and malnourishment is associated with higher overall mortality. GLIM criteria is recommended to assess the nutritional status of hospitalized patients with HCC, which is recommended and can be used as the basis for nutritional interventions.
A bibliometric analysis of HIV-1 drug-resistant minority variants from 1994 to 2022
Authors: Yan Chang , Yu Fengting , Li Mengying , Yang Xiaojie , Sun Rui , Liang Xuelei , Lao Xiaojie , Zhang Hanxi , Lv Wenhao , Hu Ying , Lai Yuan , Ding Yi , Zhang Fujie
Published: June 2024

Background
The rapid initiation of antiretroviral therapy has become an international trend, necessitating lifelong medication for all HIV patients. Sanger sequencing, as the gold standard for clinically detecting HIV drug resistance, often fails to detect mutations comprising less than 20% of the total viral population. With the advancement of detection technologies, HIV-1 DRMinVs have garnered increasing attention. However, there are few studies exploring the hotspots and trends in this field. Fortunately, bibliometrics, a novel approach to literature analysis, can fill this gap effectively.
Methods
Publications related to HIV-1 DRMinVs from 1994 to 2022 were searched on the WoSCC database. Visual knowledge maps and bibliometric analyses were generated using VOSviewers, CiteSpace, and the R package "bibliometrix."
Results
In total, 853 publications concerning HIV-1 DRMinVs were identified from 1994 to 2022, demonstrating a steady increase in publication output over the years. The United States, France, and the United Kingdom significantly lead in publication output. The main research institutions are Harvard University, University of Pittsburgh, Stanford University and National Cancer Institute. The Journal of Antimicrobial Chemotherapy holds the highest prominence among journals in this domain, while the Journal of Virology emerges as the most frequently co-cited journal. A total of 5687 authors have contributed to these publications. Among them, Vincent Calvez, Francesca Ceccherini-Silberstein, and John M. Coffin emerge as the most prolific authors, having published the highest number of articles. Additionally, Metzner, KJ emerges as the most frequently co-cited author. The main trends include the origins, molecular epidemiology, detection methods of DRMinVs, their impact on virological outcomes in drug-naïve patients, and novel research focuses primarily revolve around keywords such as "NGS," "ART," "VF," and "GRT."
Conclusions
The use of medication inevitably leads to drug resistance. For HIV-1 DRMinVs, the emergence of NGS has addressed the issue of missed detections by Sanger sequencing. However, its high cost and stringent laboratory requirements have limited its widespread application. Therefore, future research should focus on improving and refining NGS to make it simpler and more affordable, and explore when it can serve as a supplement to Sanger sequencing.
Abdominal LIPUS stimulation prevents cognitive decline in hind limb unloaded mice by regulating gut microbiota
Authors: zheng Yumei , Yu Yanan , Chen Mengyao , zhang Huiyuan , Wang Wanzhao , Fan Xiushan , Sun Lijun , Tang Liang , Ta Dean
Published: June 2024

Weightlessness usually causes disruption of the gut microbiota and impairs cognitive function. There is a close connection between gut microbiota and neurological diseases. Low intensity pulsed ultrasound (LIPUS) has a beneficial effect on reducing intestinal inflammation. So we wondered if abdominal LIPUS stimulation can have a positive impact on weightlessness induced cognitive decline by reducing intestinal dysfunction. The findings revealed that the hind limb unloaded mice exhibited evident disruption in intestinal structure and gut microbial homeostasis, along with impairment in their learning and memory capabilities. However, 4-week abdominal LIPUS treatment improved intestinal function in hind limb unloaded mice, characterized by upregulation of tight junction proteins ZO-1 and Occludin expression in the colon, increased diversity and abundance of intestinal microbiota, decreased serum lipopolysaccharide (LPS), and increased short chain fatty acids in colon contents. The hind limb unloaded mice treated with LIPUS exhibited heightened activity levels, improved exploratory tendencies, and significantly enhanced learning and memory faculties, and elevated expression of neuroadaptation-related proteins such as PSD95, GAP43, P-CREB, BDNF, and its receptor TRKB in the hippocampus. Furthermore, the hind limb unloaded mice receiving fecal transplants from the mice whose abdomens were irradiated with LIPUS displayed enhanced cognitive abilities and improved intestinal structure, akin to the outcomes observed in hind limb unloaded mice who received LIPUS abdominal treatment directly. The above results indicate that LIPUS enhances intestinal structure and microbiota, which helps alleviate cognitive impairment caused by weightlessness. LIPUS could be a potential strategy to simultaneously improve gut dysfunction and cognitive decline in astronauts or bedridden patients.
Lipid remodeling in serum and correlation with stroke in patients with leukoaraiosis
Authors: Lin Feng , Song Yige , Cao Hongi , Song Wangting , Liao Fengye , Deng Yanping , Wei Qinyu , Hong Weimin , Yao Guifeng , Sze Fat Tin Agassi , Ding Chunguang , Chen Xianyang
Published: June 2024

Background
Despite the identification of many hub lipids for stroke, the underlying pathophysiology of stroke in elderly patients with leukoaraiosis (LA) remains poorly understood, which is important for the administration of antithrombotic therapy for LA patients. This study aims to illuminate the preliminary lipid metabolic process associated with stroke in LA patients (LS).
Methods
The study cohort consisted of 215 individuals undergoing magnetic resonance imaging(MRI), from which a subset 13 patients with stroke matched with a control group, and 48 LS patients matched with 40 LA patients were selected for further investigation after exclusion. Serum lipidome was profiled by UPLC-TOF. OPLS-DA was used for classification and identifying differential metabolites. Customizing structural equation (CSE) model was applied to assess the pathway weight of novel metabolites in stroke incidence. Linear regression and matrix correlation were used to investigate the relationships between differentiated metabolites and outcomes.
Results
Using lipid profiling and multivariate statistical analysis, we screened 168 different compounds between LA and LS. Based on the enrichment and Sankey diagram of pathway, 52 lipid molecules were regarded as differential metabolites associated with glycerolipid, glycerophospholipid, and sphingolipid metabolism. After CSE weighted the pathway node molecules, we finally identified 11 key metabolites achieving a prediction, in which DG(14:0/22:4) (OR = 5.33) and Cer(d18:1/24:1) (OR = 21.44) were significant risk factors for LS. All 11 metabolites exhibited correlations with the outcome (LS incidence), with particularly heightened metabolic disruption in the presence of high blood pressure. We conducted linear regression analysis and found changes in FA16:1; O, DG(12:0/17:2) and DG(14:0/22:4) out of 11 metabolites correlated with Fazekas scores between CK and LS group. Similarly, compared with LA group, DG(14:0/22:4) (OR = 5.33, p = 0.02) and Cer(d18:1/24:1) (OR = 21.44, p = 0.068) are risk factors for LS. Especially, Cer(d18:1/24:1) and PI(22:1/20:1) were significantly associated with the LS incidence.
Conclusion
This study identified 11 metabolites as key metabolites for stroke incidence in LA patients, including subgroups divided by Fazekas scores. This study provides novel insights into lipid metabolic process from LA to LS, in which the lipid disturbance in glycolipids and glycerophospholipids, as well as the regulatory role of Cer(18:1/24:1), which are valuable for further studies of LS.
An iridium(III) complex based luminogenic probe for high-throughput screening of H2S donors in living cells
Authors: Wu Ke-Jia , Sun Wen , Sun Jian-Min , Lu Chang , Li Yan , Sun Ning , Leung Chung-Hang , Wu Chun
Published: June 2024

The scarcity of suitable high-throughput screening technology for H2S donors has hampered the discovery of H2S donors. In this study, a long-lived cyclometalated iridium complex was rationally designed as a mitochondria-targeted H2S probe to monitor the real-time dynamic change of H2S. By using time-resolved emission spectroscopy (TRES) technique, an anti-interference high-throughput screening system was developed to monitor H2S in living cells with decreased false negative results. As a proof-of-concept, three natural products were identified as potential H2S donors from a natural product library using the developed TRES probe. Notably, the discovery of allicin and diallyl trisulfide demonstrated the feasibility of this screening platform, while garlic derived allyl methyl sulfide was explored as a H2S donor candidate. The results were further validated by a commercial assay. We anticipate this high-throughput platform could facilitate the discovery of H2S donors by discriminating the endogenous interfering fluorescence from biological system.
Case Report: Prolonged Clinical Benefit of ESG401, a Novel Trophoblast Cell-Surface Antigen 2 (Trop-2) Antibody-Drug Conjugate (ADC), in a Patient with Endocrine- Refractory Hormone Receptor-Positive, HER-2 Negative Metastatic Breast Cancer
Authors: Zhao Jing , Huang Fengbo , Xu Xia , Zhang Yan , Xing Xiaoyan , Huang Jian , Qiu Fuming
Published: June 2024

Breast cancer (BC) remains a leading cause of cancer-related mortality in women, with hormone receptor-positive (HR+) tumors accounting for a significant proportion of cases. Despite advancements in endocrine therapy (ET), resistance remains a challenge in metastatic settings. The use of cyclin-dependent kinases 4/6 (CDK4/6) inhibitors in combination with endocrine therapy has notably improved survival. In China, when patients develop resistance to CDK4/6 inhibitors (CDK4/6i) or face financial constraints that prevent their use, chemotherapy becomes the standard treatment approach. This highlights an urgent need for effective treatments following CDK4/6i therapy. ESG401 is a novel Trop2-directed antibody-drug conjugate (ADC) with promising preclinical and early clinical efficacy and safety data. We report a case of a 61-year-old female with HR + HER2- metastatic breast cancer (MBC) who developed resistance to fulvestrant and subsequent chemotherapy but achieved a durable partial response (PR) lasting more than 22.5 months following ESG401 treatment. This case underscores the potential role of Trop2-directed ADCs, such as ESG401, in overcoming endocrine resistance and providing meaningful clinical benefit in heavily pretreated patients with HR+/HER2- MBC. Furthermore, the patient's exceptionally long clinical benefit distinguishes her from other patients receiving ESG401 treatment. Further exploration of the use of ESG401 in HR + HER2- MBC patients, as well as a deeper understanding of the characteristics of patients that may impact sustained efficacy, in expanded clinical trials is warranted.
Study on the control of mechanical and electrical properties of 3D printed BTO/PDMS flexible porous composites
Authors: Hao YiChen , Wang Jun , Wang Qian , Chen Jimin , Zeng Yong
Published: June 2024

Flexible piezoelectric functional composite materials have the advantages of strong plasticity and good surface adhesion, and show great potential in smart wearable devices, electronic skin and other applications. However, due to the complexity of traditional preparation process, high molding cost and poor air permeability, its further development is limited. Direct ink writing (DIW) 3D printing technology is a rapid prototyping technology, with higher flexibility, faster manufacturing speed and lower manufacturing costs, is widely used in metal, ceramic and composite material molding. In this work, a slurry system with polydimethylsiloxane (PDMS) as binder and Barium titanate (BTO) ceramic powder as piezoelectric filler was developed, the printing work of flexible porous BTO/PDMS composite material was completed, and DIW dual-nozzle printing technology was developed. The integrated flexible porous electrode - piezoelectric - electrode functional gradient structure composite was realized. The results show that the BTO/PDMS ink has the characteristics of shear thinning. When the nozzle diameter is 0.5 mm, the printing speed is 650 mm/min, and the BTO mass fraction is 80%, the flexible porous piezoelectric composite with high precision and complex structure is printed. By phase analysis of BTO/PDMS, it is found that the sample has the characteristic peak of BTO. The microstructure analysis shows that the surface of the sample has good structural fidelity and there are a few island-like pores in the interior. The mechanical test shows that the maximum tensile strength of the sample is 1.33 MPa, the elastic modulus is 1.72 MPa, the longitudinal piezoelectric coefficient d33 is 4.37 Pc/N, and the open circuit voltage VOC is 3.17 V. This work demonstrates a highly attractive method for forming flexible piezoelectric materials with “electrode-piezoelectric-electrode” structures, which, due to its simple operation, time and manufacturing cost savings, proposes solutions to key problems in current 3D ceramic manufacturing technologies.
Granulomas in common variable immunodeficiency display different histopathological features compared to other granulomatous diseases
Authors: Stigt Astrid C. , Thüsen Jan H. , Mustafa Dana A.M. , Bosch Thierry P.P. , Lila Karishma A. , Vadgama Disha , Hagen Martin van , Dalm Virgil A.S.H. , Dik Willem. A. , IJspeert Hanna
Published: June 2024

Granulomatous disease affects up to 20% of patients with common variable immunodeficiency (CVID). Granulomas are comprised of highly activated immune cells, and emerge in response to antigenic triggers. In CVID granulomas however, the underlying pathophysiology is unclear and the specific trigger remains unknown. Granuloma formation in CVID is often compared to sarcoidosis, although clinical context and prognosis differ, suggesting a different pathogenesis. The aim of this study was to investigate if the cellular organization and proteomics of granulomas in CVID is different from other granulomatous diseases. Therefore, tissue slides from formaldehyde fixed paraffin embedded biopsies obtained from patients with CVID, sarcoidosis, tuberculosis and foreign-material induced pseudo-sarcoidosis were stained with hematoxylin and eosin and assessed for histopathological characteristics. Targeted spatial protein analysis was performed, and immune fluorescent multiplex assays were used to analyze the cellular organization. Histological analysis revealed that CVID granulomas were smaller, less circumscribed, with fewer multinucleated giant cells and minimal fibrosis compared to the other granulomatous diseases. Spatial protein analysis showed that granulomas in all diseases expressed CD68, CD11c, CD44, CD127, and PD-L1. However in CVID, reduced expression of the fibrosis-related protein fibronectin, but enrichment of CD163, CD3 and FAPα inside CVID granulomas was observed. Immunofluorescence analysis conformed a different cellular organization in CVID granulomas with increased influx of neutrophils, macrophages, T and B lymphocytes. In conclusion, granulomas in CVID display a different histological and cellular organization with increased influx of myeloid and lymphoid cells, compared to sarcoidosis, tuberculosis and pseudo-sarcoidosis, indicating a distinct pathogenesis underlying granuloma formation.
Principal component analysis and clustering of proso millet genotypes based on SSR marker diversity
Authors: Santhoshkumar C. , Vaithiyalingan M. , Murugan E. , Renuka R. , Suthamathi P. , Hemalatha G.
Published: June 2024

The current study mainly aims the assessment of the principal component analysis, genetic divergence and molecular diversity studies in proso millet accessions. The conservation and utilization of plant genetic resources require the identification and characterization of germplasm. Molecular markers are commonly utilized to evaluate genetic and taxonomic association, diversity among population structure in various species. In principal component analysis, out of 15 PC components only five components were significant (to assess maximum diversity) and these five components contributed over 78.04% of total phenotypic variance. The PC1 showed positive loading values and maximum variation explaining in the traits plant height, number of basal tillers, flag leaf blade width, flag leaf blade length, peduncle length, panicle length, number of grains per panicle and number of primary inflorescence branches. Seed color shows the highest Shannon-Weaver diversity index (1.306) among all the germplasm accessions followed by leaf pubescence (0.692), growth habit (0.690), inflorescence shape (0.684) and sheath pubescence (0.604). Totally 9 alleles were amplified by 4 polymorphic markers among 24 SSR primers studied. Alleles marked by primers with a range of 2 to 3 alleles and mean of 2.25 alleles per locus. The PIC values of primers ranged from 0.45 (Pm7689) to 0.71 (Pm564). In this study three polymorphic primers exhibited PIC values of more than 0.5. In NTSYS software grouped the 72 proso millet accessions into seven major clusters by using UPGMA clustering method (Table 5). Cluster VI is the largest one which had 19 accessions followed by cluster I (18) and cluster III (18). The similarity coefficient ranges 0.11 to 0.88. lesser similarity coefficient accessions possessed higher genetic variation and hybridization of these accessions may result in desirable recombinants and more advantageous in breeding programs.
Changes in Antibiotic Resistance Before and During the COVID-19 Pandemic: Retrospective Surveillance Study in a Single Indonesian Tertiary Hospital
Authors: Sugianli Adhi Kristianto , Amelia Rachel , Tjoanatan Jerry , Tjandrawati Anna , Turbawaty Dewi Kartika
Published: June 2024

Background: Antibiotic resistance is recognized as a public health threat with significant impacts on mortality and economic burdens. Antibiotic resistance related to inappropriate empiric antibiotics, particularly during the COVID-19 pandemic. However, limited information is available about changes in antibiotic resistance before and during the pandemic in Indonesia. This study aimed to describe changes in the prevalence of antibiotic resistance among patients with proven bacterial infections before and during the COVID-19 pandemic.
Methods: A retrospective surveillance study was carried out at a single tertiary hospital to review medical records containing culture and antibiotic susceptibility data among hospitalized patients diagnosed with sepsis and COVID-19 according to the International Classification of Disease (ICD). In this context, the predefined periods were 1 January–31December 2019 and 1 March 2020–31 December 2021. The result was the percentage of resistance to selected antibiotics among the study population, stratified by gram-bacteria type, with the evaluation of changes in antibiotic resistance over time.
Results: During the observation period, 596 adult patients were diagnosed with sepsis (before COVID-19), and 2786 were diagnosed with confirmed COVID-19 (during COVID-19). The rate of culture growth in patients with sepsis was greater than that in patients with COVID-19, with values of 51.6% and 29.2%, respectively. Gram-negative bacterial isolates were predominantly found in all observation periods, accounting for 41.2% - 47.3% of the adult middle-aged group. Changes in antibiotic resistance against GNB were observed during COVID-19 (peak phase, above 20%) compared to the early phase. For gram-positive bacteria, the greatestchanges were found in the late phase, reaching 70%.
Conclusions: This study revealed that changes in antibiotic resistance before and during the COVID-19 pandemicaffected both GNB and GPB. High antibiotic use and age-related immune responses (i.e., immunosenescence) contributed to these rapid changes. Strengthening strategies, including implementing surveillance systems and antimicrobial stewardship programs and enhancing the capacity of healthcare workers, are recommended for combatting antibiotic resistance.
The study of competing endogenous RNAs regulatory network in hepatocellular carcinoma via bioinformatics
Authors: Huang Tong , Zhao Man , Mao Huajie , Bai Mengge , Zhang Jingyuan , Xia Hua , Wang Yu
Published: June 2024

Background
Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers globally and individuals diagnosed at advanced stages. The discovery of new diagnostic and prognostic markers in HCC is urgent. Circular RNAs (circRNAs) have emerged as key players in the intricate landscape of gene regulation through the competing endogenous RNA (ceRNA) mechanism. However, the ceRNA mechanism of circRNAs in HCC still remains unclear.
Methods
This study conducted a comprehensive HCC analysis using GEO database expression profiles for circRNAs, miRNAs, and mRNAs. Differentially expressed genes (DEGs) were revealed and visually presented through R-generated volcano plots and heatmaps. The STRING website and Cytoscape facilitated the construction of a protein-protein interaction (PPI) network. Functional enrichment analyses validated signaling pathways, and a circRNA-miRNA-mRNA network was constructed through Cytoscape.
Results
The study identified 86 differentially expressed mRNAs (33 upregulated, 43 downregulated) across GSE168852, GSE169289, and GSE202069 datasets. Volcano plots and Venn diagrams illustrated gene expression changes. Gene ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) analysis revealed functional insights. A PPI network identified 8 key genes (HMMR, EXO1, TOP2A, CCNB1, NUF2, CCNB2, BUB1, BUB1B) validated by GEPIA and Kaplan-Meier Plotter. The Cytoscape built ceRNA network unveiled regulatory modules involving 4 mRNAs, 9 miRNAs, and 31 circRNAs.
Conclusions
In summary, this study established circRNA-miRNA-mRNA regulatory modules, including 4 mRNAs, 9 miRNAs, and 31 circRNAs. This offers an effective bioinformatics strategy for studying HCC molecular mechanisms and prognosis. This might provide a realm of the molecular with diagnosis and prognosis biomarkers in HCC.
Improving equitable healthcare resource use: Developing a neighbourhood district nurse needs index for staffing allocation
Authors: Filipe Luís , Piroddi Roberta , Baker Wes , Rafferty Joe , Buchan Iain , Barr Ben
Published: June 2024

Background
Allocating health care resources to local areas in proportion to need is an important element of many universal health care systems, aiming to provide equal access for equal need. The UK National Health Service allocates resources to relatively large areas in proportion to need, using needs-weighted capitation formulae. However, within those planning areas, local providers and commissioners also require robust methods for allocating resources to neighbourhoods in proportion to need to ensure equitable access. We therefore developed a local resource allocation formula for NHS district nursing services for a City in the North West of England, demonstrating a novel approach for equitable resource allocation to small areas.
Methods
Using linked data from community health services, primary care, secondary care and social care, we used a zero-inflated Poisson regression to model the number of district nursing services contacts for each individual based on predictors of need, while including the supply of district nurses per head to account for historical supply induced patterns. Individual need was estimated based on the predictions from this model, keeping supply fixed at the average. We then compared the distribution of district nurses between neighbourhoods, based on our formula, to the current service staffing distribution.
Results
Key predictors of need for district nursing services were age, deprivation, chronic diseases such as, cardiovascular disease, chronic liver disease, neurological disease, mental ill health, learning disability living in a nursing home, living alone, and receiving palliative care. Need for district nursing services was highly weighted towards older and more deprived populations. The current distribution of staff was, however, more correlated with age than deprivation. Moving to a needs-based staffing distribution would shift staff from less deprived areas to more deprived areas potentially reducing inequalities.
Conclusion
A neighbourhood-level model for needs for district nursing is a useful tool that can potentially improve the allocation of resources, addressing unmet need and inequalities.
Open Education on Social Entrepreneurship: A comparative study between Mexico and Bolivia to Scale up Complex Thinking
Authors: Alvarez-Icaza Inés , Marco-Tórrez Liz Katherine , Rondón-Jara Evelyn
Published: June 2024

The Open Education movement has tremendous transformative potential in developing countries and marginalized communities. The implementation of the OpenEdR4C platform, a digital educational resource for entrepreneurship education, was an example of this potential. As an open resource for scaling up complex thinking competencies in higher education students and lifelong learners, the platform has been presented to various institutions and organizations in Mexico and Bolivia. The objective of this article is to show the impact of the digital course on social entrepreneurship on the development of complex thinking skills of the workshop participants. The study was conducted using mixed methods, evaluating the perception of the performance levels of the participants and analyzing their opinions on the benefits brought by the platform. The results showed that (a) the level of performance in complex thinking competence improved after the formative experience, (b) the platform can be a convenient resource for training higher education students and lifelong learners, and (c) social entrepreneurship is a valuable topic to be trained with open educational resources. This study is a contribution to the transformative efforts made by developers of digital open educational resources and educators to build different approaches of competence for work training and social entrepreneurship skills development.
Novel Approach to Exploring Protease Activity and Targets in HIV-associated Obstructive Lung Disease using Combined Proteomic-Peptidomic Analysis
Authors: Samorodnitsky Sarah , Kruk Monica , Lock Eric F. , Kunisaki Ken M. , Morris Alison , Leung Janice M. , Weise Danielle , Mehta Subina , Parker Laurie L. , Jagtap Pratik D. , Griffin Timothy J. , Wendt Chris H.
Published: June 2024

Background: Obstructive lung disease (OLD) is increasingly prevalent among persons living with HIV (PLWH). However, the role of proteases in HIV-associated OLD remains unclear.
Methods: We combined proteomics and peptidomics to comprehensively characterize protease activities. We combined mass spectrometry (MS) analysis on bronchoalveolar lavage fluid (BALF) peptides and proteins from PLWH with OLD (n=25) and without OLD (n=26) with a targeted Somascan aptamer-based proteomic approach to quantify individual proteases and assess their correlation with lung function. Endogenous peptidomics mapped peptides to native proteins to identify substrates of protease activity. Using the MEROPS database, we identified candidate proteases linked to peptide generation based on binding site affinities which were assessed via z-scores. We used t-tests to compare average forced expiratory volume in 1 second per predicted value (FEV1pp) between samples with and without detection of each cleaved protein and adjusted for multiple comparisons by controlling the false discovery rate (FDR).
Findings: We identified 101 proteases, of which 95 had functional network associations and 22 correlated with FEV1pp. These included cathepsins, metalloproteinases (MMP), caspases and neutrophil elastase. We discovered 31 proteins subject to proteolytic cleavage that associate with FEV1pp, with the top pathways involved in small ubiquitin-like modifier mediated modification (SUMOylation). Proteases linked to protein cleavage included neutrophil elastase, granzyme, and cathepsin D.
Interpretations: In HIV-associated OLD, a significant number of proteases are up-regulated, many of which are involved in protein degradation. These proteases degrade proteins involved in cell cycle and protein stability, thereby disrupting critical biological functions.
No Causal Association Between Gut Microbiota and Kawasaki Disease: A Two-Sample Mendelian Randomization Study
Authors: Wang Sibao , Luo Gang , Ji Zhixian , Pan Silin
Published: June 2024

Background: Despite previous observational studies linking gut microbiota to Kawasaki disease (KD), these findings remain controversial. This study aimed to explore the association between gut microbiota and KD at a genetic level, using a two-sample Mendelian randomization (MR) analysis.
Methods: A two-sample MR study utilized summary statistics of gut microbiota from the largest genome-wide association study meta-analysis by the MiBioGen consortium. The causal link between gut microbiota and KD was examined using inverse variance weighted, MR Egger, weighted median, simple mode, weighted mode, and MR-PRESSO methods. Reverse MR analysis was conducted on bacteria identified as causally linked to KD in the initial MR study. Cochran’s Q and Rucker’s Q statistics quantified the heterogeneity among instrumental variables.
Results: Inverse variance weighted estimates suggested no genetic causal correlation with KD for the following taxa: genus Bifidobacterium(p = 0.774, OR 95% CI = 0.876 [0.355–2.163]), genus FamilyXIIIAD3011group(p = 0.945, OR 95% CI = 0.979 [0.539–1.780]), genus LachnospiraceaeUCG004(p = 0.987, OR 95%CI = 1.005 [0.542–1.863]), genus RuminococcaceaeNK4A214group (p = 0.453, OR 95%CI = 1.469 [0.538–4.009]), genus RuminococcaceaeUCG002 (p = 0.835, OR 95% CI = 1.092 [0.478–2.494]), genus LachnospiraceaeUCG001 (p = 0.996, OR 95%CI = 0.998 [0.482–2.066]), genus Bacteroides (p = 0.595, OR 95%CI = 0.831 [0.419–1.648]), genus Olsenella (p = 0.414, OR 95%CI = 1.312 [0.684–2.516]), genus Lactococcus (p = 0.870, OR 95%CI = 0.962 [0.600–1.541]), family Rhodospirillaceae (p = 0.995, OR 95%CI = 1.002 [0.550–1.827]), family FamilyXIII (p = 0.894, OR 95%CI = 1.093 [0.298–4.009]), family BacteroidalesS24 (p = 0.604, OR 95%CI = 0.849 [0.456–1.578]), family Ruminococcaceae (p = 0.524, OR 95%CI = 0.692 [0.223–2.148]), and class Bacilli (p = 0.905, OR 95%CI = 0.967 [0.561–1.667]). The reverse MR analysis revealed no significant causal effect of KD on gut microbiota. No significant heterogeneity of instrumental variables or horizontal pleiotropy was observed.
Conclusion: Our bidirectional causal inference analysis revealed no genetic causal relationship between gut microbiota and KD. Confounding factors might have influenced the observed association in observational studies. Further research requires more advanced MR analysis methods, and larger-scale GWAS datasets.
Drivers of summer Arctic sea-ice extent in CMIP6 large ensembles revealed by information flow
Authors: Docquier David , Massonnet François , Ragone Francesco , Sticker Annelies , Fichefet Thierry , Vannitsem Stéphane
Published: June 2024

Arctic sea-ice extent has strongly decreased since the beginning of satellite observations in the late 1970s. While several drivers are known to be implicated, their respective contribution is not fully understood. Here, we apply the Liang-Kleeman information flow method to five different large ensembles from the Coupled Model Intercomparison Project Phase 6 (CMIP6) over the 1970-2060 period to investigate the extent to which fluctuations in winter sea-ice volume, air temperature and ocean heat transport drive changes in subsequent summer Arctic sea-ice extent. This allows us to go beyond classical correlation analyses. Results show that air temperature is the most important controlling factor of summer sea-ice extent at interannual timescale, and that winter sea-ice volume and Atlantic Ocean heat transport play a secondary role. If we replace air temperature by net shortwave and downward longwave radiations, we find that the sum of influences from both radiations is almost similar to the air temperature influence, with the longwave radiation being dominant in driving changes in summer sea-ice extent. Finally, we find that the influence of air temperature is more prominent during periods of large sea-ice reduction and that this temperature influence has overall increased since 1970.
The FlbC transcription factor contributes to the generation of strain heterogeneity in Fumagillin mycotoxin production in Aspergillus fumigatus
Authors: Tanaka Yutaka , Asagiri Ikumi , Komiya Rei , Yamazaki Hiroyuki , Yagi Akiho , Uchida Ryuji , Sasaki Masato
Published: June 2024

Aspergillus fumigatus shows inter-strain heterogeneity in the repertoire of secondary metabolites such as mycotoxin fumagillin but the mechanism by which this heterogeneity arises in those production is still not understood. Here, we investigates the effect of the flbC gene on fumagillin production in A. fumigatus by introducing flbC deletions into laboratory strains, A1151, A1159, and A1280 from different backgrounds and examines the effect of the flbC gene on inter-strain heterogeneity. We found that, although all three laboratory strains were capable of producing fumagillin, there was heterogeneity in the effects of flbC gene deletion on fumagillin production. This heterogeneity may be dependent on differences in the expression levels of the fma gene family involved in fumagillin production and different levels of transcriptional activation by transcription factors FapR and LaeA. The flbC gene expression level peaks at the same time as peak mycelial growth but shows differential expression level, suggesting that the differences among strains in the range of expression levels are dependent on differences in the upstream expression of flbC. Thus, our findings show that the different interactions between flbC and factors regulating the expression of fumagillin gene cluster are the probable cause for heterogeneity in fumagillin production in the organism.
MPI, pinning and core count- performanceanalysis in numerical oceans acoustics
Authors: Melic Alena
Published: June 2024

The large- scale numerical simulation/solution in three dimensions (3D) of partial differential equations requires significant com-putational resources, regardless of the physics domain (e.g. numericaloceans acoustics, electromagnetic fields, computational fluid dynamics. . . ).The utilization of the Message Passing Interface (MPI) offers a distinctadvantage in enabling large- scale simulations/solutions based on thesedifferential equations. This streamlines the approximation process significantly. By employing MPI, scientists and engineers model effortlesslythe complex interactions from physical parameters in various physics domains. This empowers them to make informed decisions in various fields,from e.g. marine engineering to environmental monitoring. This papershows the efficiency result of a specific software application for the numerical solution of a partial differential equation in numerical oceansacoustics in 3D on a high-performance computer (HPC) with the respective number of cores, pin assignment and MPI Version
Restoration of the endemic hermatypic coral Cladocora caespitosa in the Mediterranean Sea: coral gardening based on micro-fragmentation
Authors: Cardinale Pierfrancesco , Danovaro Roberto
Published: June 2024

Cladocora caespitosa is the only reef-building zooxanthellate coral in the Mediterranean Sea. It forms beds of colonies, sporadically aggregating in extensive reef-like structures. The carbonate deposition of C. caespitosa enhances habitat complexity, supports biodiversity, and contributes to carbon sequestration. This species has been increasingly threatened by anthropogenic pressures. Due to its decline, the International Union for the Conservation of Nature (IUCN) included C. caespitosa in the endangered species list. Here we explored the available knowledge on tropical coral reefs to develop a protocol for the ecological restoration of this Mediterranean species. In this preliminary study, we exploited naturally occurring dislodged fragments as donor material and successfully implemented micro-fragmentation and nursery-rearing techniques on this species, designing a protocol for future restoration interventions. We reported that micro-fragmented C. caespitosa has optimal survival and growth rates surpassing those of naturally occurring juvenile colonies. We also showed that C. caespitosa fragments subjected to a strong heatwave, bleached but survived and recovered after the re-establishment of lower temperatures. Bleached individuals of C. caespitosa were able to grow, although to a much lower rates than those in healthy conditions. The coral gardening proposed here is highly successful, and can be operated at large spatial scales.
Impact of IL-8 on Survival after TARE in HCC: A Comprehensive Investigation and External Validation from the SORAMIC Trial
Authors: Schindler Aaron , Fischer Janett , Beeskow Anne-Bettina , Lincke Thomas , Ebel Sebastian , Seehofer Daniel , Denecke Timm , Veelken Rhea , Sabri Osama , Öcal Osman , Seidensticker Max , Berg Thomas , Bömmel Florian
Published: June 2024

Purpose
In the treatment of hepatocellular carcinoma (HCC) with transarterial radioembolization (TARE), identifying reliable biomarkers for predicting survival outcomes remains a critical challenge. We aimed to address this gap by investigating the significance of serum cytokines associated with inflammation as potential biomarkers for the selection of patients for TARE.
Methods
Our retrospective study involved 161 patients diagnosed with HCC who underwent Y90 radioembolization at our medical center between 2010 and 2020. Serum samples from a subset of 78 patients were retrospectively analyzed to determine the concentrations of pro-inflammatory cytokines. The results from the prospective SORAMIC trial were used for independent validation.
Results
With a median overall survival of 36 weeks (range 4-436), our study showed the strongest correlation between 12-week survival and IL-8 levels before treatment (p < 0.001), while other relevant interleukins, interferon-α2, INF-γ, TNF-α and MCP-1 were not associated with survival. IL-8 levels below the cut-off of 190 pg/mL were significantly associated with increased 12-week and 24-week survival, with hazard ratios of 19.01 (95% CI: 2.29-157.89) and 2.57 (95% CI: 1.05–6.31), respectively (p = 0.006 and p = 0.039, respectively). In the adjusted multivariate analysis, the 190 pg/mL cut-off for IL-8 remained independently associated with 12- (p = 0.011) and 24-week survival (p = 0.039). Similarly, the SORAMIC population showed a strong association between IL-8 levels and 36-week survival (p = 0.03).
Conclusion
Our study emphasizes the pivotal role of IL-8 as a valuable parameter, demonstrating its potential for predicting treatment outcomes and assessing liver function in patients with HCC undergoing TARE. The robustness of these findings warrants further validation.