bluuebunny/crossref_metadata_2025 huggingface dataset:
Giant icebergs increase mixing and stratification in upper-ocean layers
Authors: Lucas Natasha , Brearley James , Hendry Katherine , Spira Theo , Braakmann-Folgmann Anne , Abrahamsen Einar Povl , Meredith Michael , Tarling Geraint
Published: June 2024

Ice sheet mass loss is one of the clearest manifestations of climate change, with Antarctica discharging mass into the ocean via the melting of glacial ice or through calving. This calving produces icebergs which can modify ocean water properties, often at great distances from source. This affects upper ocean physics and primary productivity, with implications for atmospheric carbon drawdown. Detailed understanding of iceberg modification of ocean waters has hitherto been hindered by a lack of proximal measurements. Here, unique measurements of a giant iceberg from an underwater glider quantifies meltwater effects on the physical and biological processes in the upper layers of the Southern Ocean, a region disproportionately important for global heat and carbon sequestration. Iceberg basal melting erodes seasonally-produced Winter Water (WW) layer stratification, normally forming a strong potential energy barrier to vertical exchange of surface and deep waters, whilst freshwater runoff increases and shoals near-surface stratification. Nutrient-rich deeper waters, incorporating terrigenous loaded meltwater, are ventilated to below this stratification maxima, providing a potential mechanism for alleviating critical biological limiting components. Regional historical hydrographic data demonstrates similar stratification changes during the passage of another large iceberg, suggesting that they may be an important pathway of aseasonal WW modification.
Network-based global analysis of the cellular senescence process and senescence phenotype in the peripheral sensory neurons of the dorsal root ganglia
Authors: Kawabata Sora , Iijima Hirotaka , Kanemura Naohiko , Murata Kenji
Published: June 2024

Accumulation of senescent neurons in the dorsal root ganglion (DRG) is an important tissue phenotype that causes age-related degeneration of peripheral sensory nerves. Senescent neurons are neurons with arrested cell cycle that have undergone cellular senescence but remain in the tissue and play various biological roles. To understand the accumulation of senescent neurons in the DRG during aging, we aimed to elucidate the mechanism that induces cellular senescence in DRG neurons and the role of senescent DRG neurons. We integrated multiple public transcriptome datasets for DRGs, which represent cell bodies in neurons, and sciatic nerve, which represents axon in neurons, using network medicine-based bioinformatics analysis to account for axon-cell body interaction involved in cellular senescenc. Network medicine-based bioinformatics analysis revealed that age-related Mapk3 decline leads to impaired cholesterol metabolism and biosynthetic function in axons, resulting in compensatory upregulation of Srebf1, a transcription factor involved in lipid and cholesterol metabolism, which in turn leads to CDKN2A-mediated cellular senescence. Furthermore, this analysis revealed that senescent DRG neurons develop a senescence phenotype characterized by activation of antigen-presenting cells via upregulation of Ctss as a hub gene. B cells inferred as antigen-presenting cells activated by Ctss, and CD8-positive T cells inferred as cells that receive antigen presentation from the B cells.
Hepatic fibroblast growth factor 21 is required for curcumin or resveratrol in exerting their metabolic beneficial effect in male mice
Authors: Jin Tianru , Feng Jia Nuo , Shao Weijuan , Yang Lin , Pang Juan , Ling Wenhua , Liu Dinghui , Wheeler Michael , He Housheng
Published: June 2024

Conclusion and significance: We conclude that hepatic FGF21 is required for curcumin or resveratrol in exerting their major metabolic beneficial effect. The recognition that FGF21 as the common target of dietary interventions brings us a novel angle in understanding metabolic disease treatment and prevention. It remains to be explored how various dietary interventions regulate FGF21 expression and function, via certain common or unique gut-liver or gut-brain-liver axis.
Background: Our mechanistic understanding on metabolic beneficial effects of dietary polyphenols has been hampered for decades due to the lack of functional receptors for those compounds and their extremely low plasma concentrations. Recent studies by our team and others have suggested that those dietary polyphenols may target gut microbiome and gut-liver axis and that hepatic fibroblast factor 21 (FGF21) serves as a common target for various dietary interventions.
Methods: Utilizing liver-specific FGF21 null mice (lFgf21-/-), we are asking a straightforward question: Is hepatic FGF21 required for curcumin or resveratrol, two typical dietary polyphenols, in exerting their metabolic beneficial effect in obesogenic diet-induced obese mouse models.
Results: On low-fat diet feeding, no appreciable defect on glucose disposal was observed in male or female lFgf21-/- mice, while fat tolerance was impaired in male but not in female lFgf21-/- mice, associated with elevated serum triglyceride (TG) level, reduced hepatic expression of the Ehhadh and Ppargc1a, which encodes the two downstream effectors of FGF21. On high-fat-high-fructose (HFHF) diet challenge, Fgf21fl/fl but not lFgf21-/- mice exhibited response to curcumin intervention on reducing serum TG, and on improving fat tolerance. Resveratrol intervention also affected FGF21 expression or its downstream effectors. Metabolic beneficial effects of resveratrol intervention observed in HFHF diet-challenged Fgf21fl/fl mice were either absent or attenuated in lFgf21-/- mice.
BECC-engineered live-attenuated Shigella vaccine candidates display reduced endotoxicity with robust immunogenicity in mice
Authors: Ernst Robert , Sherman Matthew , Michalski Jane , Das Sayan , Yang Hyojik , Chandrasekaran Lakshmi , O'Meara Timothy , Dowling David , Levy Ofer , Barnoy Shoshana , Venkatesan Malabi
Published: June 2024

Shigella spp. infection contributes significantly to the global disease burden, primarily affecting young children in developing countries. Currently, there are no FDA-approved vaccines against Shigella, and the prevalence of antibiotic resistance is increasing, making therapeutic options limited. Live-attenuated vaccine strains WRSs2 (S. sonnei) and WRSf2G12 (S. flexneri 2a) are highly immunogenic, making them promising vaccine candidates, but possess an inflammatory lipid A structure on their lipopolysaccharide (LPS; also known as endotoxin). Here, we utilized bacterial enzymatic combinatorial chemistry (BECC) to ectopically express lipid A modifying enzymes in WRSs2 and WRSf2G12, as well as their respective wild-type strains, generating targeted lipid A modifications across the Shigella backgrounds. Dephosphorylation of lipid A, rather than deacylation, reduced LPS-induced TLR4 signaling in vitro and dampened endotoxic effects in vivo. These BECC-modified vaccine strains retained the phenotypic traits of their parental strains, such as invasion of epithelial cells and immunogenicity in mice without adverse endotoxicity. Overall, our observations suggest that BECC-engineered live attenuated vaccines are a promising approach to safe and effective Shigella vaccines.
A unique and biocompatible corneal collagen crosslinking in vivo
Authors: Gulzar Ayesha , Kaleli Humeyra Nur , Köseoğlu Gülsüm Deniz , Hasanreisoğlu Murat , Yıldız Ayşe , Şahin Afsun , Kizilel Seda
Published: June 2024

Corneal crosslinking (CXL) is a widely applied technique to halt the progression of ectatic diseases through increasing the thickness and mechanical stiffness of the cornea. This study investigated the biocompatibility and efficiency of a novel CXL procedure using ruthenium and blue light in rat corneas and evaluated parameters important for clinical application. To perform the CXL procedure, the corneal epithelium of rats was removed under anaesthesia, followed by the application of a solution containing ruthenium and sodium persulfate (SPS). The corneas were then exposed to blue light at 430 nm at 3 mW/cm2 for 5 minutes. Rat corneas were examined and evaluated for corneal opacity, corneal and limbal neovascularization, and corneal epithelial regeneration on days 0, 1, 3, 6, 8, and 14. On day 28, the corneas were isolated for subsequent tissue follow-up and analysis. CXL with ruthenium and blue light showed rapid epithelial healing, with 100 % regeneration of the corneal epithelium and no corneal opacity on day 6. The ruthenium group also exhibited significantly reduced corneal (p<0.01) and limbal neovascularization (p<0.001). Histological analysis revealed no signs of cellular damage or apoptosis, which further confirms the biocompatibility and nontoxicity of our method. Confocal and scanning electron microscopy (SEM) images confirmed high density of collagen fibrils, indicating efficient crosslinking and enhanced structural integrity. This study is unique that demonstrates in vivo safety, biocompatibility, and functionality of ruthenium and blue light CXL. This approach can prevent toxicity caused by UV-A light and can be an immediate alternative compared to the existing crosslinking procedures that have side effects and clinical risks for the patients.
Comparative responses to demethylating therapy in animal models of osteosarcoma
Authors: Huang Shan , Ren Ling , Beck Jessica A. , Patkar Sushant , Osuna Maria Angeles Lillo , Cherukuri Aswini , Mazcko Christina , Krum Susan A. , LeBlanc Amy K.
Published: June 2024

Background
The demethylating agent decitabine (DAC) effectively inhibits tumor growth and metastasis by targeting ESR1 methylation to restore estrogen receptor alpha (ERα) signaling and promoting cellular differentiation in models of human osteosarcoma (OSA). Whether this pathway can be targeted in canine OSA patients is unknown.
Methods
Canine OSA tumor samples were tested for ERα expression and ESR1 promoter methylation. Human (MG63.3) and canine (MC-KOS) OSA cell lines and murine xenografts were treated with DAC in vitro and in vivo, respectively. Samples were assessed using mRNA sequencing and tissue immunohistochemistry.
Results
ESR1 is methylated in a subset of canine OSA patient samples and the MC-KOS cell line. DAC treatment led to enhanced differentiation as demonstrated by increased ALPL expression, and suppressed tumor growth in vitro and in vivo. Metastatic progression was inhibited, particularly in the MG63.3 model, which expresses higher levels of DNA methyltransferases DNMT1 and 3B. DAC treatment induced significant alterations in immune response and cell cycle pathways.
Conclusion
DAC treatment activates ERα signaling, promotes bone differentiation, and inhibits tumor growth and metastasis in human and canine OSA. Additional DAC-altered pathways and species- or individual-specific differences in DNMT expression may also play a role in DAC treatment of OSA.
Academic Stress and Attitudes Toward Seeking Professional Psychological Help among Vietnamese students: the mediating role of Emotional Intelligence
Authors: Nguyen-Thi Thanh-Thao , Nguyen Dat Tan , Le Huu Minh , Le Cong Minh , Hua Thuy Doan , Nguyen-Hoang Bao-Nhu , Tran-Chi Vinh-Long , Nguyen-Thi Kieu-Lan
Published: June 2024

Background: Emotional Intelligence is considered a noteworthy concept in the academic environment due to the theoretical significance and practical implications. The objectives of this research were to investigate (1) the correlation between academic stress and emotional intelligence, and (2) the mediating role of attitudes toward seeking professional psychological help.
Methods: An online questionnaire was administered to a random sample of 908 Vietnamese secondary school students from December 2023 to January 2024. Three scales were employed to gather demographic variables and self-reported data, including The Wong and Law Emotional Intelligence Scale, The Educational Stress Scale for Adolescents, and Attitudes Toward Seeking Professional Psychological Help.
Results: The findings indicated substantial differences across many variables, such as gender, grade, and academic performance ranking. The investigation identified substantial significant relationships, including emotional intelligence of others’ emotion appraisal positively affects self-expectation, while self-emotion appraisal negatively influences self-expectation. The analysis determined significant relationships, including others’ emotion appraisal positively affects self-expectation, while self-emotion appraisal negatively influences self-expectation. Use of emotion positively associates with the openness of seeking professional help. Moderation analyses revealed age moderating others’ emotion appraisal and despondency, self-emotion appraisal and the openness of seeking professional help.
Conclusion: Emotional intelligence exerts a substantial influence on both academic stress levels and attitudes toward seeking professional psychological assistance. The results are analysed in accordance with the guidelines for conducting mixed-methods research. Workshops and awareness sessions for educators and students on emotional intelligence can beconducted with the cooperation of all parties concerned because of the endorsement of all stakeholders.
Real-world efficacy of nanoliposomal irinotecan in patients with advanced pancreatic cancer
Authors: Decraecker Marie , Joncour Sophie Le , Aurillac Valérie , Sangnier Maïté , Ducerf Camille , Berroneau Aude , Rouleau Laetitia , Tougeron David , Laplace Christophe , Madau Magali , Dumon Camille , Perrier Herve , Blanc Jean-Frédéric
Published: June 2024

Background.
In the randomized NAPOLI-1 trial, nanoliposomal irinotecan (Nal-Iri) combined with fluorouracil and folinic acid provided considerable survival increase for patients with metastatic pancreatic ductal adenocarcinomas who had received gemcitabine-based therapy. However, patients included in clinical trials often differ from those encountered in practice. A real-world study was required to assess the efficacy and safety of Nal-Iri in patients with poor prognoses for whom quality of life preservation was essential.
Methods.
We conducted an observational, retrospective national multicenter phase 4 study of patients with advanced pancreatic cancers treated using Nal-Iri combined with fluorouracil and folinic acid in clinical practice. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. We used a nomogram validated from a concordance index of eight clinicobiological variables to predict OS.
Results
A total of 58 patients with advanced pancreatic adenocarcinomas who received Nal-Iri combined with fluorouracil and folinic acid in three medical centers between March 2020 and September 2022 were included. The median duration of Nal-Iri treatment was 3.6 (range 1.9–8.8) months. The median follow-up time from the start of first-line treatment was 26.2 (16.5–44.8) months. Of all patients, 20.7% received Nal-Iri in a second-line setting, but most (n = 37 patients; 63.8%) received Nal-Iri in a third-line setting. Forty-two patients (72.4%) had previously been treated with irinotecan. The median OS from the time of Nal-Iri initiation was 6.0 (2.6–13.1) months, and the median PFS was 5.8 (3.2–11.4) months. Patients who received Nal-Iri in a second-line setting exhibited significantly better OS than patients who received Nal-Iri in a third-line setting or later (p < 10− 3). Patients who had previously received irinotecan exhibited significantly lower OS compared with patients who were irinotecan-naïve (p < 10− 3).Our nomogram demonstrated excellent prediction of 6-month and 1-year survivals (p < 10 − 3).
Conclusions.
Nal-Iri combined with fluorouracil and folinic acid was particularly effective in second-line settings and irinotecan non-pre-treated patients. The nomogram demonstrated excellent prediction of survival under real-world conditions.
Visual imagination can influence visual perception – towards an experimental paradigm to measure imagination
Authors: Mozhdehfarahbakhsh Azadeh , Hecker Lukas , Joos Ellen , Kornmeier Jürgen
Published: June 2024

During visual imagination a perceptual representation is activated in the absence of sensory input. This is sometimes described as seeing with the mind’s eyes. A number of physiological studies indicate that the brain uses more or less the same neural resources for real visual perception and visual imagination. The intensity of visual imagination is typically assessed with questionnaires, while more objective measures are missing. Aim of the present study was, to test a new experimental paradigm that may allow to objectively quantify imagination. For this we used priming and adaptation effects during observation of ambiguous figures. Our perception of an ambiguous stimulus is unstable and alternates spontaneously between two possible interpretations. If we first observe an unambiguous stimulus variant (the conditioning stimulus), the subsequently presented ambiguous stimulus can either be perceived in the same way as the test stimulus (priming effect) or in the opposite way (adaptation effect) as a function of the conditioning time. We tested for these classical conditioning effects (priming and adaptation) using an ambiguous Necker Cube and Letter /Number stimuli as test stimuli and unambiguous variants thereof as conditioning stimuli. In a second experimental condition, we tested whether the previous imagination of an unambiguous conditioning stimulus variant – instead of its observation – can have similar conditioning effects on the subsequent test stimulus. We found no systematic classical conditioning effect on the group level, neither for the cube stimuli nor for the letter/number stimuli. However, highly significant correlations between effects of Real and Imaginary condition were observed for both stimulus types. The absence of classical condition effects at the group level may be explained by using only one conditioning time, which may fit with individual priming and adaptation constants of some of our participants but not of others. Our strong correlation results indicate that observers with clear classical conditioning effects have about the same type (priming or adaptation) and intensity of imaginary conditioning effects. As a consequence, not only past perceptual experiences but also past imaginations can influence our current percepts. This is further confirmation that the mechanisms underlying perception and imagination are similar. Our post-hoc qualitative observations from three self-defined aphantasic observers makes our paradigm a promising objective measure to identify aphantasia.
The impact of surgery on butterfly gliomas - A real-life study of biopsy vs. surgical resection
Authors: Picarelli Helder , Medeiros Vitor Macedo Brito , Castro Pedro Henrique Fonseca , Carneiro Guilherme Bezerra , Matsumura Bruno Massanori , Cordeiro Augusto Magno Tranquezi , Yamaki Vitor Nagai , Figueiredo Eberval Gadelha , Teixeira Manoel Jacobsen
Published: June 2024

Background
Despite the extent of resection affecting the overall survival of patients with gliomas, cytoreduction in patients with butterfly gliomas (BG) remains controversial. Contemporary studies suggest that wide removal is feasible, but there is a lack of controlled, randomized, multicenter studies on the subject. The aim of this study was to evaluate the impact of safe maximal surgical resection (SMSR) as a primary treatment strategy in patients with BG.
Methods
30 consecutive patients, primarily treated with neurosurgery, were categorized into Group-A when SMSR was equal to or greater than 50% and Group-B when it was less than 50% (biopsy). The groups were studied and compared for clinical, epidemiological, functionality, survival time (ST), and progression-free survival (PFS) characteristics. Results were analyzed by descriptive and inferential statistics.
Results
The most frequent tumors were glioblastoma IDH-wild type, WHO grade 4. Most patients (80%) had KPS < 70%, however, there was no significant worsening of functionality associated with interventions. Wider resection (Group-A) was associated with a better Kaplan-Meier curve and ST (68.35 versus 17.32 weeks, p = 0.014). PFS was also longer in this group (57.70 versus 4.77 weeks, p = 0.012). In multivariate analysis, resections > 50% were associated with reduced risk of recurrence (HR = 0.20, 95% CI 0.06–0.67, p = 0.009). Complication rates and functional decline were similar between groups.
Conclusion
Surgical resections (> 50%) in patients with BG improved ST and PFS without a significant increase in morbidity and dysfunction.
FAP-α is an effective tool to evaluate stroma invasion of lung adenocarcinoma
Authors: Xiong Siping , Fan Huan , Guo Yimin , Sun Ruixiang , Ma Hongmei , Xiang Yali , Zeng Chao
Published: June 2024

The main difficulty in the diagnosis of atypical in situ adenocarcinoma lies in the distinction between true and false stromal invasion. Moreover, how to identify local alveolar wall collapse in situ lung adenocarcinoma and how to identify whether the trapped adenoid structure around scar is an invasion component have become the key points for accurate diagnosis of lung adenocarcinoma. In the present study, we detected 40 cases of lung adenocarcinoma in situ and 40 cases of invasive adenocarcinoma by using immunohistochemical techniques. We found FAP-α had not immunreactivity in the stroma of adenocarcinoma in situ. However, it stained in the stroma of invasive areas in lung adenocarcinoma. FAP-α staining pattern could represent hyperplastic myofibroblast and demonstrated the true invasion of stroma. This study provides strong evidence that FAP-α is an effective tool to evaluate the presence or absence of stroma invasion of lung adenocarcinoma. Our findings will contribute to the accurate diagnosis of lung invasive adenocarcinoma.
Examining the Role of Peace of Mind, Gratitude, and Positive Reappraisal in Predicting Psychological Well-being Among College Students
Authors: Du Wei , Liu Limin
Published: June 2024

This study investigated the relationships between gratitude, positive reappraisal, peace of mind, and psychological well-being among Chinese college students using a cross-sectional design. Participants included 336 undergraduate students from various disciplines, recruited from four universities in mainland China. Self-reported measures assessed gratitude, positive reappraisal, peace of mind, and psychological well-being. Preliminary analyses ensured data quality and addressed potential common method bias. Confirmatory factor analysis supported the hypothesized measurement model, and structural equation modeling revealed significant direct effects of gratitude, positive reappraisal, and peace of mind on well-being. Additionally, gratitude and positive reappraisal demonstrated significant indirect effects on well-being mediated by peace of mind. Measurement invariance testing confirmed that the model operated equivalently across gender groups, supporting the robustness and generalizability of the findings. These results highlight the importance of gratitude, positive reappraisal, and peace of mind in promoting psychological well-being among college students, particularly in high-pressure academic environments.
An exploratory study:Cadonilimab(AK104) and Lenvatinib combined with stereotactic body radiotherapy in the conversion therapy of potentially resectable hepatocellular carcinoma
Authors: Fu Jiajia , 章 金丰 , Liu Dongen , Lin Zhenyu , Liu Hongli , Hu Jianli , Zhang Tao , Tang Jing , Xue Jun
Published: June 2024

Background
Surgery is one of the standard treatments for long-term survival in patients with hepatocellular carcinoma(HCC). However, the majority of HCC patients are initially diagnosed at an advanced stage, less than 30% of patients can undergo curative resection, and the risk of postoperative recurrence is usually more than 50%. Conversion therapy creates the opportunity for radical resection of potentially resectable HCC, but its exact protocol and effectiveness remain controversial. As a first-line systematic treatment for advanced HCC, immunocombined targeted therapy has shown good efficacy. Studies have shown that some patients can obtain surgical resection opportunities through radiotherapy, and radiotherapy combined with immunotherapy has also shown good clinical benefits in conversion therapy trials. Therefore, this study aims to explore the efficacy and safety of Cadonilimab(AK104) and Lenvatinib combined with Stereotactic body radiotherapy(SBRT) in HCC conversion therapy, which may provide a new therapeutic strategy for HCC patients in the future.
Methods/design:
An exploratory clinical study is planned to enroll 27 patients with potentially resectable HCC. Eligible patients underwent tumor evaluation before receiving Cadonilimab(AK104) and Lenvatinib combined with SBRT conversion therapy, after the second cycle of treatment, and before surgery, and were followed up every 6 weeks after surgery. The primary endpoint was objective response rate(ORR), and secondary endpoints were surgical resection rate, major pathological response(MPR), duration of response(DOR), disease control rate(DCR), progression-free survival(PFS), time to disease progression(TTP), and overall survival(OS), and adverse events(AEs).
Discussion
This trial will evaluate the efficacy and safety of Cadonilimab(AK104) and Lenvatinib combined with SBRT in the conversion therapy of potentially resectable HCC patients, providing clinical data for a new mode of conversion therapy for HCC, combining immune and targeted therapy with radiotherapy. At present, there is no consensus standard protocol for HCC conversion therapy, and more prospective studies are needed to further explore the treatment modalities and their effects.
Trial registration:
Chinese Clinical Trial Registry: ChiCTR2300068781, Registered on February 28, 2023.
Sewage digestate compost as a growing medium: implications for manganese uptake in tomato plants
Authors: Aurdal Siv Mari , Bakke Anders , Krogstad Tore , Haraldsen Trond Knapp , Remberg Siv Fagertun
Published: June 2024

Aims
Container-grown crops need reliable growing media that provide optimal conditions for plant growth. The traditional media peat and coconut coir are increasingly being replaced with sustainable alternatives. However, the availability of essential nutrients, such as manganese (Mn), in compost-based media remains a concern. This study therefore aimed to investigate Mn deficiencies in tomato seedlings grown in a compost consisting of 30% v/v sewage digestate and 70% v/v garden waste.
Methods
Tomato plants were cultivated from seeds under nursery conditions for eight weeks. The physical and chemical properties of the growing media, including bulk density, total pore space, air content, water retention, pH, electrical conductivity (EC), and essential nutrients, were assessed. Plant growth parameters such as height, leaf number, chlorophyll content, and fresh/dry weight were measured, alongside nutrient analysis.
Results
Despite the high Mn content in the compost, the tomato plants exhibited significant Mn deficiency. Factors contributing to this deficiency included high pH, abundant organic matter, and elevated iron and calcium levels, which likely formed insoluble compounds, reducing Mn availability. Additionally, the compost's low water retention and structural changes limited plant growth.
Conclusions
The findings emphasize the need to consider Mn availability in compost with a sewage-based component. This study highlights the complexities of nutrient availability in sustainable growing media and the importance of optimizing compost composition to support healthy plant growth.
Bioinformatics Analysis of the Cuprotosis Gene in Immune Infiltration of Chronic Kidney Disease
Authors: Liu Yu , Yang Mengfan , Huang Youqun , Ye Naijing , Zhang Caibin , Luo Yuechan , Zou Hequn
Published: June 2024

Background：Chronic kidney disease is currently a major public health challenge worldwide, and modeling based on gene expression profiling is essential to guide individualized treatment of the disease. According to recent studies, cuprotosis, one of the forms of death of cells, appears to contribute to the progression of various diseases. Therefore, the present study aims to explore clusters associated with cuprotosis genes in chronic kidney disease, delve into immune infiltration, and construct predictive models.
Methods：The GSE37171 (GPL570) dataset was downloaded from the Gene Expression Omnibus for analyzing expression profiling and immune characterization of cuprotosis regulators in CKD. Samples were classified into different clusters based on cuprotosis-related genes (CRGs) of kidney disease. Differential expression pathways and biological functions among clusters were identified through gene set variation analysis. The weighted gene co-expression network analysis algorithm was adopted to identify specific differentially expressed genes of clusters. A machine learning model was built to construct and validate nomogram risk prediction maps.
Results：A total of seven cuprotosis-related genes are differential genes between chronic kidney disease and control group, with differences in immune infiltration between the two groups. Two different clusters are identified based on the expression profiles of the cuprotosis-related genes. And according to the differences in immune infiltration, it is hypothesized that the prognosis of Cluster 2 may be worse. Cluster 1 may be associated with cellular lipid anabolism, fibrosis, signal reception, inflammation, and other processes, while Cluster 2 is more closely related to DNA replication and binding, cellular protein synthesis and transport, peroxisome, etc. The predictive performance of the four selected machine learning classifiers is compared and a prediction model is developed, which provides the highest predictive validity in the test cohort (AUC = 0.992), indicating satisfactory performance. The model is verified to exhibit good predictive efficacy.
Conclusion：The study systematically illustrates the complex relationship between cuprotosis and chronic kidney disease and develops a promising predictive model to assess cuprotosis subtypes in patients with the disease, revealing the underlying molecular mechanisms that lead to its
A single-cell eQTL atlas of the human cerebellum reveals vulnerability of oligodendrocytes in essential tremor
Authors: Rouleau Guy , Castonguay Charles-Etienne , Aboasali Farah , Medeiros Miranda , Becret Theodore , Schmilovich Zoe , Khayachi Anouar , Rajput Alex , Dion Patrick
Published: June 2024

Essential tremor (ET) is a movement disorder characterized by an upper-limb postural and action tremor. It is one of the most common neurological disorders, affecting 1% of the worldwide population. Despite strong evidence for genetic factors driving the aetiology of ET, the underlying pathophysiology remains poorly understood. To understand the effects of genetic risk factors in ET on the cerebellum, the brain region thought to be affected by the disease, we built a population-scale single-cell atlas of the human cerebellar cortex comprised of over 1 million cells from 109 individuals. Using single-cell expression quantitative trait loci and mendelian randomization, we found evidence of ET-associated variants in the BACE2 locus causally linked to its downregulation in cerebellar oligodendrocytes. We highlight a genetically vulnerable population of BACE2-expressing immature oligodendrocytes, suggestive of demyelination. We also find dysfunctional processes affecting interactions between Golgi cells, Purkinje layer interneurons, and oligodendrocytes in ET. Our study suggests a crucial role for cerebellar oligodendrocytes in the pathogenesis of ET.
UW Supplementation with AP39 Improves Liver Viability Following Static Cold Storage
Authors: McLean S Taggart , Holkup Saige , Tchir Alexandra , Mojoudi Mohammadreza , Hassan Madeeha , Taveras Christopher , Ozge S Ozgur , James F Markmann , Yeh Heidi , Uygun Korkut , Longchamp Alban
Published: June 2024

Static cold storage of donor livers at 4°C incompletely arrests metabolism, ultimately leading to decreases in ATP levels, oxidative stress, cell death, and organ failure. Hydrogen Sulfide (H2S) is an endogenously produced gas, previously demonstrated to reduce oxidative stress, reduce ATP depletion, and protect from ischemia and reperfusion injury. H2S is difficult to administer due to its rapid release curve, resulting in cellular death at high concentrations. AP39, a mitochondrially targeted, slow-release H2S donor, has been shown to reduce ischemia-reperfusion injury in hearts and kidneys. Thus, we investigated whether the addition of AP39 during 3-day static cold storage can improve liver graft viability. At the end of storage, livers underwent six hours of acellular normothermic machine perfusion, a model of transplantation. During simulated transplantation, livers stored with AP39 showed reduced resistance, reduced cellular damage (ALT and AST), and reduced apoptosis. Additionally, bile production and glucose, as well as energy charge were improved by the addition of AP39. These results indicate that AP39 supplementation improves liver viability during static cold storage.
Complete genome sequence and probiotic characterization of Lactobacillus delbrueckii subsp. indicus DC-3 isolated from traditional indigenous fermented milk
Authors: Chaudhari Deepti N. , Ahire Jayesh J. , Devkatte Anupama N. , Kulthe Amit S.
Published: June 2024

In this study, Lactobacillus delbrueckii subsp. indicus DC-3 was isolated from Indian traditional indigenous fermented milk Dahi and identified using whole genome sequencing. The safety of the strain was evaluated using both genetic and phenotypic analyses, such as the presence of virulence factors, mobile and insertion elements, plasmids, antibiotic resistance, etc. Besides this, the strain was comprehensively investigated for in vitro probiotic traits, biofilm formation, antibacterials, and exopolysaccharide (EPS) production. In results, the strain showed a single circular chromosome (3,145,837 bp) with a GC content of 56.73%, a higher number of accessory and unique genes, an open pan-genome, and the absence of mobile and insertion elements, plasmids, virulence, and transmissible antibiotic resistance genes. The strain was capable of surviving in gastric juice (83% viability at 3 h) and intestinal juice (71% viability at 6 h) and showed 42.5% autoaggregation, adhesion to mucin, 8.7% adhesion to xylene, and 8.3% adhesion to Caco-2 cells. The γ-hemolytic nature, usual antibiotic susceptibility profile, and negative results for mucin and gelatin degradation ensure the safety of the strain. The strain produced 10.5 g/L of D-lactic acid and hydrogen peroxide, capable of inhibiting and co-aggregating Escherichia coli MTCC 1687, Proteus mirabilis MTCC 425, and Candida albicans ATCC 14053. In addition, the strain showed 90 mg/L EPS (48 h) and biofilm formation. In conclusion, this study demonstrates that L. delbrueckii subsp. indicus DC-3 is unique and different than previously reported L. delbrueckii subsp. indicus strains and is a safe potential probiotic candidate.
Deep Learning-based Multi-class Object Tracking With Occlusion Handling Mechanism in Uav Videos
Authors: Micheal A Ancy , Micheal A Annie , Gopinathan Anurekha , Barathi B U Anu
Published: June 2024

Unmanned Aerial Vehicles (UAVs) play a crucial role in tracking-based applications, particularly in real-time situations such as rescue missions and surveillance. However, tracking objects with occlusion can be challenging, as it involves reidentifying objects with consistent identities. To address this issue, a novel multi-class object tracking methodology with occlusion handling has been proposed. This methodology employs You Only Look Once Neural Architecture Search (YOLO-NAS) and confluence-based object detection. YOLO-NAS has demonstrated superior detection with quantization-aware blocks and selective quantization, which is utilized for object tracking. Additionally, a Densely Connected Bidirectional LSTM tracker has been developed to use the feature representation and object locations from the detector. Furthermore, the methodology incorporates occlusion handling object association to re-identify objects in scenarios with occlusion or out-of-view situations. To evaluate the proposed framework, comparisons have been made with state-of-the-art models using UAV123, UAVDT, and VisDrone datasets. A detailed ablation study has been performed with UAV123 dataset. The proposed framework is observed to outperform other models with MOTA of 94.53%, Recall of 97.8%, Precision of 97.19%, F-score of 97.49% and Rel.ID of 9.26%.
No evidence of Bartonella infections in host-seeking Ixodes scapularis and I. pacificus ticks in the United States
Authors: Bai Ying , McClung Kristin L. , Osikowicz Lynn M. , Maes Sarah , Eisen Rebecca J.
Published: June 2024

Background
Bartonella spp. infect a variety of vertebrates throughout the world with generally high prevalence. Several Bartonella spp. are known to cause diverse clinical manifestations in humans and have been recognized as emerging pathogens. These bacteria are mainly transmitted by blood sucking arthropods, such as fleas and lice. The role of ticks in the transmission of Bartonella sp. is unclear.
Methods
A recently developed quadruplex PCR amplicon next generation sequencing approach that targets Bartonella-specific fragments on gltA, ssrA, rpoB, and groEL was applied to test host-seeking Ixodes scapularis ticks (n = 1641; consisting of 886 nymphs and 755 adults) collected in 23 states of the eastern United States and Ixodes pacificus ticks (n = 966; all nymphs) collected in California in the western United States for the presence of Bartonella DNA. These species were selected because they are common human biters and serve as vectors of pathogens causing the greatest number of vector-borne diseases in the United States.
Results
No Bartonella DNA was detected in any of the ticks tested by any target.
Conclusions
Owing to the lack of Bartonella detection in a large number of host-seeking Ixodes sp. ticks tested across a broad geographic region, our results strongly suggest that I. scapularis and I. pacificus are unlikely to contribute more than minimally, if at all, to transmission of Bartonella spp..
Exacerbation of Schistosomiasis Japonica in Shroom2-knockout Mice
Authors: Liu Wanling , Xiu Lei , Li Tao , Jiang Ning , Wan Yanmin , Jia Liqiu , Cun Yi , Wang Xiaoling , Lin Siran , Xie Yuxiang , Zhang Wei , Qiu Chao , Li Jian , Hu Wei , Wu Jing , Zhang Wenhong
Published: June 2024

Background
Shroom2 is an actin-binding protein known for its involvement in cell motility regulation and actin cytoskeleton remodeling. Schistosome eggs trigger the formation of granulomas, organized immune aggregates surrounding the eggs. However, the specific roles of Shroom2 in granuloma formation and evolution have not been elucidated.
Methods
Shroom2 knockout (KO) mice were utilized to investigate the impact of Shroom2 on the formation of Schistosomiasis japonicum (S. japonicum) egg granulomas. This study aimed to analyze the effects of Shroom2 deficiency on the host response to S. japonicum infection.
Results
KO mice exhibited a significantly elevated mortality rate when infected with S. japonicum. Furthermore, extensive lung tissue necrosis was observed following the implantation of S. japonicum eggs. The lungs of Shroom2 knockout mice displayed hyperinflammation after S. japonicum egg implantation, and the percentage of major immune cell populations was reduced.
Conclusion
Given the aforementioned results, we inferred that Shroom2 deficiency compromises the host’s ability to effectively defend against parasitic infections. This study highlights the crucial role of Shroom2 in immune response regulation during S. japonicum infection and suggests that Shroom2 is a potential key player in granuloma formation and overall host defense mechanisms.
One-step litchi like bimetallic nanozyme-assisted indirect competitive immunoassay for the detection of acetamiprid in vegetables
Authors: Liu BeiBei , Zhai Rongqi , Zhang Jie , Liu Guangyang , Huang Xiaodong , Lv Jun , Chen Jing , Liu Junjiang , Jin Maojun , Wang Jing , Xu Donghui , Chen Ge
Published: June 2024

The conventional enzyme-linked immunosorbent assay is limited in its ability to satisfy the increasing demand for advanced immunoassay due to its reliance on natural enzymes, low sensitivity, and narrow detection range. The development of nanozyme-assisted immunoassay is a viable approach to overcome this constraint. Therefore, a one-step litchi like nanozyme-assisted indirect competitive immunoassay was designed for the detection of acetamiprid. In this assay, litchi-like Au@Pt nanozyme (inexpensive, simple preparation, stable, and adjustable catalytic activity) were directly conjugated with antibodies as signal probes without using peroxidase-conjugated affinipure goat antimouse IgG (IgG-HRP). Acetamiprid competed with haptens to bind the Au@Pt probes. Subsequently, Au@Pt nanozymes, which exhibit peroxidase-like activity, were added to catalyze the oxidation of colorless 3,3′,5,5′-tetramethylbenzidine (TMB) in the presence of H2O2. The linear range, sensitivity, relative standard deviations (RSDs) ranged and limit of detection (LOD) were 1.85 ~ 327.19 µg/L, 25.58 µg/L, 0.46 ~ 10.35% and 0.78 µg/L, respectively, satisfying the requirement of immunoassay detection. In conclusion, the method exhibited high sensitivity, reproducibility and wide linear range for the detection of acetamiprid, while eliminating the need for IgG and simplifying the experimental procedure. The proposed indirect competitive immunoassay has great value for onsite sensitive detection of acetamiprid in vegetables.
The role of Tyr34 in proton-coupled electron transfer of human manganese superoxide dismutase
Authors: Borgstahl Gloria , Azadmanesh Jahaun , Slobodnik Katelyn , Struble Lucas , Cone Erika , Dasgupta Medhanjali , Lutz William , Kumar Siddhartha , Natarajan Amarnath , Coates Leighton , Weiss Kevin , Myles Dean , Kroll Thomas
Published: June 2024

Human manganese superoxide dismutase (MnSOD) plays a crucial role in controlling levels of reactive oxygen species (ROS) by converting superoxide (O2●−) to molecular oxygen (O2) and hydrogen peroxide (H2O2) with proton-coupled electron transfers (PCETs). The reactivity of human MnSOD is determined by the state of a key catalytic residue, Tyr34, that becomes post-translationally inactivated by nitration in various diseases associated with mitochondrial dysfunction. We previously reported that Tyr34 has an unusual pKa due to its proximity to the Mn metal and undergoes cyclic deprotonation and protonation events to promote the electron transfers of MnSOD. To shed light on the role of Tyr34 MnSOD catalysis, we performed neutron diffraction, X-ray spectroscopy, and quantum chemistry calculations of Tyr34Phe MnSOD in various enzymatic states. The data identifies the contributions of Tyr34 in MnSOD activity that support mitochondrial function and presents a thorough characterization of how a single tyrosine modulates PCET catalysis.
Catalyst and base-free, direct oxidation of chitin to lactic acid with hydrogen peroxide
Authors: Du Xiao , Li Tengfei , Wang Lumei , Ren Dezhang , Huo Zhibao
Published: June 2024

In recent years, the research on the conversion of chitin to high value-added chemicals has attracted more and more attention. At present, the method of preparing lactic acid from chitin mostly uses strong base or catalyst. These reaction systems have disadvantages such as corrosion of containers and harm to human body. Herein, a simple and effective method to convert chitin to organic acids in catalyst and base-free conditions is developed. The use of H2O2 only can efficiently convert chitin to organic acids in the absence of bases and catalysts. Under the optimal conditions of 30 mg chitin, 2.1 mL water, 0.9 mL H2O2 at 230 oC for 1.5 h, the lactic acid yield of chitin can reach 58.2% and the total organic acid yield can reach 84.0%. This work provides an efficient method for the resource utilization of chitin biomass.
Observation of higher-order time-dislocation topological modes
Authors: Lee Ching Hua , Zhang Jia-hui , Mei Feng , Li Yi , Ma Jie , Xiao Liantuan , Jia Suotang
Published: June 2024

Topological dislocation modes resulting from the interplay between spatial dislocations and
momentum-space topology have recently attracted significant interest. Here, we theoretically and
experimentally demonstrate time-dislocation topological modes which are induced by the interplay
between temporal dislocations and Floquet-band topology. By utilizing an extra physical dimension to represent the frequency-space lattice, we implement a two-dimensional Floquet higher-order
topological phase and observe time-dislocation induced π-mode topological corner modes in a three-
dimensional circuit metamaterial. Intriguingly, the realized time-dislocation topological modes exhibit spatial localization at the temporal dislocation, despite homogeneous in-plane lattice couplings across it. Our study opens a new avenue to explore the topological phenomena enabled by the interplay between real-space, time-space and momentum-space topology.
An assessment of postoperative pain management in a Ghanaian Hospital
Authors: Antwi Sara Agyemang , Tandoh Augustine , Woode Prof. Eric
Published: June 2024

Objective: Pain is an inevitable byproduct of surgery. Successful perioperative pain management is an ethical goal, and health professionals are obligated to limit complications and speed up patient recovery. This study aimed to examine the extent of pain relief and the impact of pain on patients’ quality of life.
Methods: This study included 217 surgical patients who underwent a variety of surgeries. The Brief Pain Inventory-Long Form (BPI-LF) and Medical Short Form-36 (SF-36) were successfully administered to 183 patients at one week and one month after surgery, respectively. The data thus obtained were analysed using SPSS (version 25).
Results: Among the 183 patients surveyed, 80.2% (n=174) were females, and 19.8% (n=43) were males. The mean age was 34.21 years (SD ±10.989). The percentage of pain relief ranged from 50-100%, and the average percentage of pain relief after the one-week interval was 80.05 ± SD 11.266. The Cronbach’s alpha values obtained for the 11 BPI items (pain severity and functional interference) were significant. The pain management index-1 (PMI-1 using ‘pain at its worst’) showed a mean of -0.7814 ± 1.127, indicating pain management inadequacy during the first 48 hrs after surgery. The nature of the surgery may have an impact on the quality of life of the patient.
Conclusion: Pain may be undermanaged in the first 48 hrs after surgery; however, pain management after one week was adequate.
Klasse und/oder Klassismus?
Authors: Wellgraf Stefan
Published: June 2024

In den letzten Jahren hat sich im deutschsprachigen Raum eine Kontroverse um die Verwendung der Begriffe ‚Klasse‘ und ‚Klassismus‘ entwickelt. In der Debatte stehen sich marxistisch ausge-richtete Vertreter:innen der Klassentheorie und die eher identitätstheoretisch argumentierenden Protagonist:innen des Klassismusansatzes skeptisch, teilweise sogar feindselig gegenüber. Davon ausgehend, dass Begriffsfragen weder kontext- noch folgenlos sind, reflektiere ich zunächst die Potenziale und Fallstricke dieser beiden Begriffsverwendungen. Anschließend zeige ich am Beispiel meiner Forschungen zu Berliner Hauptschulen, dass sich die Ansätze auch als komplementäre, einander ergänzende Zugänge verstehen lassen. Die Empirische Kulturwissenschaft/Europäische Ethnologie ist in besonderer Weise dazu geeignet, verschiedene Ansätze miteinander zu verbinden und somit zu einer vielschichtigen Klassenanalyse beizutragen.