bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensory and Chemical Characteristics of Seasoning Made from Tempe Gembus Flour with Sugar and Salt Added
Authors: Afifah Raudhatul , Listyaningrum Ratna Sari , Amelianawati Mae
Published: June 2024

Gembus tempeh flour contains high levels of glutamate which can be used as a flavoring. The aim of this research is to determine the sensory and chemical characteristics of the flavoring ingredients of tempe gembus flour. The formulation ingredient for this research product is tempeh gembus from tofu dregs from the Cibuntu tofu making industry. Flour is made by curing tempeh for 3 days at 35°C, then slicing and drying at 70°C for 2 hours, then grinding and sifting using 80 mesh. The formulation was determined through two stages of sensory testing. Phase I sensory testing included the Duo-Trio differentiation test and hedonic test, using two samples of tempeh gembus flour formulation and a commercial MSG product as a control. Preferences are assessed using the parameters of color, aroma, taste and overall rating. Analysis of data from the differentiation test results uses the Chi-square test, while analysis of hedonic test data uses the Mann-Whitney test. The results of the phase I sensory test were used as a control in the phase II sensory test and compared with the sugar-salt addition formulation with a ratio of tempe gembus flour, salt and sugar of 5:3:2. Chemical testing was carried out which included testing water content, salt content and protein content. The test results showed that the sample with added sugar and salt had a water content of 4.6%, a salt content of 22.56%, a protein content of 7.74%, and panelists preferred sensory properties compared to the control.
Penerapan Sistem Ketertelusuran Internal dalam Pengolahan Tuna Sirip Kuning (Thunnus albacares) di PT ABC, Denpasar, Bali
Authors: Khairunnisa Anis , Utami Ni Made Dwi Rahayu
Published: June 2024

Ikan tuna merupakan jenis ikan yang bernilai ekonomis tinggi dan banyak dicari di laut Indonesia. Tingginya permintaan pasar terhadap produk tuna memerlukan adanya jaminan terhadap keamanan dan pengawasan mutu, salah satunya melalui penerapan sistem ketertelusuran (traceability). Penelitian ini bertujuan untuk mengidentifikasi tahapan proses pengolahan tuna sirip kuning dan mengamati penerapan sistem ketertelusuran secara internal di PT ABC, Denpasar. Metode penelitian menggunakan metode deskriptif kualitatif dengan teknik pengumpulan data melalui pengamatan langsung dan wawancara dengan pihak yang berkompeten, misalnya tim Quality Control dan tim Quality Assurance. Hasil penelitian menunjukkan terdapat 23 tahapan proses pengolahan ikan tuna sirip kuning mulai dari penerimaan bahan baku hingga pengiriman. Setiap tahapan proses memiliki penanggung jawab (Person in-charge) dalam mendokumentasikan kegiatan berdasarkan sistem paper-based. Bentuk pendokumentasian dalam bentuk formulir harian dengan sistem pengkodean dalam bentuk kode tulisan yang menunjukkan informasi tertentu. Perusahaan diharapkan dapat mengembangkan sistem berbasis elektronik agar informasi yang diperoleh lebih real-time dan terintegrasi.
The role of TGF-β in the electrotactic reaction of mouse 3T3 fibroblasts in vitro
Authors: Ciesielska Patrycja , Lasota Slawomir , Bobis-Wozowicz Sylwia , Madeja Zbigniew
Published: June 2024

Endogenous electric fields (EFs) serve as a crucial signal to guide cell movement in processes such as wound healing, embryonic development, and cancer metastasis. However, the mechanism underlying cell electrotaxis remains poorly understood. A plausible hypothesis suggests that electrophoretic or electroosmotic forces may rearrange charged components of the cell membrane, including receptors for chemoattractants which induce asymmetric signaling and directional motility. This study aimed to explore the role of Transforming Growth Factor Beta (TGFβ) signaling in the electrotactic reaction of 3T3 fibroblasts. Our findings indicate that inhibiting canonical and several non-canonical signaling pathways originating from the activated TGF-β receptor does not hinder the directed migration of 3T3 cells to the cathode. Furthermore, suppression of TGF-β receptor expression does not eliminate the directional migration effect of 3T3 cells in the electric field. Additionally, there is no observed redistribution of the TGF-β receptor in the electric field. However, our studies affirm the significant involvement of Phosphoinositide 3-Kinase (PI3K) in electrotaxis, suggesting that in our model, its activation is likely associated with factors independent of TGFβ action.
Middle ear anatomy and implant sizes: correlates and the need for uniform implant dimensions
Authors: Lenarz Thomas , Becker Moritz , Warnecke Athanasia , Giesemann Anja , Prenzler Nils Kristian , Steinhardt Uwe , Schurzig Daniel
Published: June 2024

Introduction

Conductive hearing loss describes an insufficient sound transfer of the middle ear, often caused by defects or absence of the ossicles. Depending on the specific middle ear dimensions and the kind of defect, surgeons can choose from a variety of passive implants to reconstruct the middle ear and hence restore sound transmission. However, the latter is only achieved if the optimal implant size is available and selected for each individual patient.

Methods

Anatomical dimensions relevant for middle ear reconstruction were assessed within high-resolution clinical imaging data of 50 patients (100 ears). The ranges of these dimensions were then compared to implant types and sizes available from different manufacturers.

Results

In general, total and partial prostheses seem to cover the whole range of anatomical variations. A lack of stapesplasty implants was found for particularly small anatomies. Various implant lengths of all types far exceed dimensions necessary for successful restoration of sound transmission. In some cases, implant lengths are not clearly specified by the manufacturer. Tympanic membrane and stapes axis were not in line for any of the investigated middle ears.

Conclusion

Clear specifications of implant lengths are crucial to allow for successful hearing restoration, and clinics often need to have more than one implant type to cover the entire range of anatomical variations they may encounter. There appears to be an unmet clinical need for smaller stapesplasty implants. Devices which allow for an angular adjustment between distal and proximal end appear to mimic the orientation of the ossicles more naturally.
Anti-inflammatory effects of thymol: an emphasis on the molecular interactions through in vivo approach and molecular dynamic simulations
Authors: Islam Muhammad Torequl , Bappi Mehedi Hasan , Bhuia Md Shimul , Ansari Siddique Akber , Ansari Irfan Aamer , Shill Manik Chanda , Albayouk Tala , Saleh Na’il , El-Shazly Mohamed , El-Nashar Heba A. S.
Published: June 2024

Thymol (THY), as the natural monoterpene phenol, acts against oxidative stress and inflammatory processes. This study aimed to evaluate the anti-inflammatory effects and possible molecular mechanisms of THY via formalin-induced mouse and egg albumin-induced chick models alongside molecular docking and molecular dynamic (MD) simulations. THY (7.5, 15, and 30 mg/kg) was investigated, compared to celecoxib and ketoprofen (42 mg/kg), as anti-inflammatory standards. THY dose-dependently and significantly (p < 0.05) decreased paw-licking and edema diameter parameters in formalin (phases I and II) and egg albumin-induced models. Moreover, THY (15 mg/kg) exerted better anti-inflammatory effects in combination with the standard drug ketoprofen than alone and with celecoxib. In silico studies demonstrated elevated binding affinities of THY with cyclooxygenase-2 (COX-2) than the COX-1 enzyme, and the ligand binds at a similar location where ketoprofen and celecoxib interact. The results of MD simulations confirmed the stability of the test ligand. THY exerted anti-inflammatory effects on Swiss mice and young chicks, possibly by interacting with COX-2. As a conclusion, THY might be a hopeful drug candidate for the management of inflammatory disorders.
Comparative analysis of intestinal microbiota composition between free-ranged captive yak populations in Nimu County
Authors: Zhu Yanbin , Lu Sijia , Cidan Yangji , Wang Hongzhuang , Li Kun , Basang Wangdui
Published: June 2024

The intestinal microbiota assumes a pivotal role in modulating host metabolism, immune responses, overall health, and additional physiological dimensions. The structural and functional characteristics of the intestinal microbiota may cause alterations within the host’s body to a certain extent. The composition of the gut microbiota is associated with environmental factors, dietary habits, and other pertinent conditions. The investigation into the gut microbiota of yaks remained relatively underexplored. An examination of yak gut microbiota holds promise in elucidating the complex relationship between microbial communities and the adaptive responses of the host to its environment. In this study, yak were selected from two distinct environmental conditions: those raised in sheds (NS, n=6) and grazed in Nimu County (NF, n=6). Fecal samples were collected from the yaks and subsequently processed for analysis through 16S rDNA and ITS sequencing methodologies. The results revealed that different feeding styles result in significant differences in the Alpha diversity of fungi in the gut of yaks, while the gut microbiota of captive yaks was relatively conserved. In addition, significant differences appeared in the abundance of microorganisms in different taxa, phylum Verrucomicrobiota was significantly enriched in group NF while Firmicutes was higher in group NS. At the genus level, Akkermansia, Paenibacillus, Roseburia, Dorea, UCG_012, Anaerovorax and Marvinbryantia were enriched in group NF while Desemzia, Olsenella, Kocuria, Ornithinimicrobium and Parvibacter were higher in group NS (P<0.05 or P<0.01). There was a significant difference in the function of gut microbiota between the two groups. The observed variations are likely influenced by differences in feeding methods and environmental conditions both inside and outside the pen. The findings of this investigation offer prospective insights into enhancing the yak breeding and expansion of the yak industry.
Promoting L2 learners’ critical thinking skills: the role of social constructivism in reading class
Authors: Le Ha Van , Nguyen Long Quoc
Published: June 2024

Introduction

In the rapidly evolving digital landscape, the imperative for success has increasingly spotlighted the essential need for students to develop critical thinking and reading skills as key competencies for the 21st century. This study sought to explore the potential of constructivism to enhance learners’ critical thinking and reading abilities, alongside evaluating their receptiveness to this pedagogical approach.

Methods

A mixed-methods research design was employed, combining a quasi-experimental framework with semi-structured interviews. The quasi-experimental component compared the effectiveness of constructivist and traditional teacher-centered methods in promoting critical thinking skills. Semi-structured interviews were conducted to gauge participants’ satisfaction with the constructivist approach and to gather qualitative data on their experiences.

Results

The investigation yielded two principal findings. First, the constructivist approach significantly outperformed traditional teacher-centered methods in promoting critical thinking skills among students. Second, the majority of participants reported a high level of satisfaction with the constructivist method, attributing this to the approach’s facilitation of deeper knowledge acquisition and increased opportunities for interaction with peers and instructors.

Discussion

Theoretical implications of this study underscore the value of constructivism in fostering an engaging and interactive learning environment conducive to the development of critical analytical skills. Practically, the findings advocate for educational practitioners and institutional leaders to consider the integration of constructivist strategies in reading sessions to bolster students’ critical thinking and reading competencies. Moreover, it emphasizes the necessity for educators to receive comprehensive training on the nuances of constructivist pedagogy to ensure its effective implementation. This study thus contributes to the pedagogical discourse by affirming the efficacy of constructivism in enhancing critical cognitive skills and by outlining a pathway for its successful adoption in educational settings.
Effectiveness and safety of once-weekly semaglutide: findings from the SEMACOL-REAL retrospective multicentric observational study in Colombia
Authors: Buenaventura-Collazos Daisy C. , García-Ramos Andrés F. , Balcázar-Valencia Carlos M. , Aguilar-Londoño Carolina , Coronel-Restrepo Nicolás , Monsalve-Arango Claudia Y. , Cuesta-Castro Diana P. , Ramírez-Rincón Alex
Published: June 2024

Introduction

Diabetes stands as one of the leading causes of death worldwide. Glucagon-like peptide-1 receptor agonists rank among the most effective medications for lowering blood glucose and body weight, as well as reducing cardiovascular risk in individuals with diabetes. Observational studies complement experimental evidence in new settings, different populations, and real-world healthcare practices.

Methods

A multicentric observational study of adults with type 2 diabetes treated with once-weekly subcutaneous semaglutide in four health centers in Colombia was conducted. The protocol for the present study was not pre-registered.

Results

Data from 186 patients were included. Most patients were women (57%) with a mean age of 62.8 ± 12.1 years. One year of once-weekly semaglutide usage was associated with a mean reduction in HbA1C of −1.47% (95% CI −1.76, −1.17), weight loss of −4.23 kg (95% CI −5.34, −3.12), and albumin/creatinine ratio of −18.6 mg/g (95% CI −60.2, −5.9). Approximately half the treated patients achieved a level of HbA1c ≤7% by the end of follow-up. Adverse events were rare and consistent with clinical trial safety profiles.

Conclusion

In Colombia, administering semaglutide subcutaneously once a week over a 1-year period led to an average weight loss of 4.2 kg and a decrease of 1.4% in HbA1c.
Association between thyroid function and nonalcoholic fatty liver disease: a dose-response meta-analysis
Authors: Xiang Liu-lan , Cao Yu-tian , Sun Jing , Li Rui-han , Qi Fang , Zhang Yu-juan , Zhang Wen-hui , Yan Lou , Zhou Xi-qiao
Published: June 2024

Background

Thyroid hormones (THs) have been found that it is closely associated with the onset and progression of non-alcoholic fatty liver disease (NAFLD). However, the current study could not verify the intrinsic relationship between thyroid hormones and NAFLD, which requires further research.

Methods

The searches of studies reported both TH level in serum and NAFLD were performed in PubMed, Web of Science, Cochrane Library, and Embase databases. We combined an overall meta-analysis with a dose-response meta-analysis to assess the correlation and dose-response relationship between thyroid function levels and the risk of NAFLD.

Results

Overall, 10 studies were included with a total of 38,425 individuals. We found that the non-linear dose-response model showed that for every 1 ng/dL increase in FT4, the risk of NAFLD was reduced by 10.56% (p=0.003). The odds ratios (ORs) for NAFLD with high free triiodothyronine (FT3) exposure compared to those with low FT3 were 1.580 (95% CI 1.370 to 1.830, I2 = 0.0%, p<0.001) in the overall meta-analysis. The continuous variable meta-analysis indicated that individuals with high levels of TSH (SMD=1.32, 95% CI 0.660 to 1.970, p<0.001) had significantly higher levels of liver fibrosis than those with low levels.

Conclusions

Our findings only validate that there is a correlation between the occurrence of NAFLD and abnormal levels of THs, and it is expected that more observational studies will still be conducted in the future to further demonstrate the relationship between thyroid hormones and NAFLD.

Trial registration

Registered number in PROSPERO: CRD42023405052.
Pelvic ultrasound and pubertal attainment in girls with sexual precocity: the pivotal role of uterine volume in predicting the timing of menarche
Authors: Cattoni Alessandro , Russo Gianni , Capitoli Giulia , Rodari Giulia , Nicolosi Maria Laura , Molinari Silvia , Tondelli Daniele , Pelliccia Ciretta , Radaelli Silvia , Arosio Andrea Mario Luciano , Fontana Katia , Tattesi Giulia , Passoni Paolo , Boneschi Annalisa , Giavoli Claudia , Meroni Silvia Laura Carla , Stancampiano Marianna Rita , Garuti Elda , Biondi Andrea , Balduzzi Adriana , Bizzarri Carla
Published: June 2024

Introduction

Among girls assessed for pubertal precocity, pelvic ultrasound (pUS) may represent a pivotal tool to predict the time expected to elapse between sonographic assessment and the onset of menarche (TUS-M). Accordingly, the present analysis is meant to define the statistical relationship between sonographic parameters and TUS-M, in order to identify the most reliable predictor of the timing of menarche.

Methods

Retrospective, multicenter analysis. Girls assessed for sexual precocity and showing sonographic and clinical findings consistent with pubertal onset upon referral were considered eligible. Patients treated with GnRH analogues were excluded and only those who had subsequently achieved complete and spontaneous pubertal attainment and for whom the exact date of menarche was available were included. Overall, we enrolled 184 girls from five tertiary care Italian Centers.

Results

The time elapsed (months) between baseline endocrine assessment and spontaneous achievement of menarche showed a negative statistically significant correlation (p<0.0001) with LH (r:-0.61), FSH (r:-0.59), estradiol (r:-0.52) and stimulated LH values (r:-0.58). Among pUS parameters, ovarian volume (r:-0.17 left, -0.30 right) and uterine body-to-cervix ratio (r:-0.18) poorly correlated with TUS-M, while uterine diameters (r:-0.61 longitudinal, -0.64 anteroposterior) and volume (r:-0.70) achieved a highly statistical significance (p<0.0001). Uterine volume (UV) showed a negative logarithmic relationship with TUS-M and represented the most reliable predictor of the timing of menarche in uni- and multivariable analyses (p <0.001). ROC analyses identified the UV thresholds that best predict the onset of menarche within 18, 12 and 6 months, respectively: 3.76, 6.02 and 8.80 ml.

Conclusion

The logarithm of UV shows the best statistical performance in predicting the timing of menarche in girls assessed for pubertal precocity. Accordingly, we developed a user-friendly online application that provides clinicians with an estimation of the months expected to elapse before menarche, based on the UV recorded upon pUS.
Environmental hotspots, frontiers and analytical framework of Blue Carbon research: a quantitative analysis of knowledge map based on CiteSpace
Authors: Zhang Lipai
Published: June 2024

Blue Carbon is increasingly popular worldwide, and it also belongs to circular economy field which would last a long period in academy. To further understand the development and characteristics of Blue Carbon, this study uses CiteSpace software to perform quantitative analysis on literature published on Web of Science and Chinese CNKI database with the main topic of “Blue Carbon.” The results show that: (1) Since 2009, increasing attention has been paid to Blue Carbon research, among which the United States, Australia and China are the leading countries. (2) Keywords such as “Blue Carbon,” “mangrove,” “carbon sequestration” and “carbon neutrality” are the high-frequency keywords appearing both in China and the World in recent years. (3) Spartina alterniflora, soil organic carbon, livestock, trophic cascade, biodiversity and seagrass ecosystem clustering are hot topics related to international Blue Carbon research, while organic carbon, seagrass-conservation, methodology, sustainable development, climate change, carbon neutralization, coastal zone and carbon storage are hot topics related to Chinese Blue Carbon research. In addition, based on the research trends of Blue Carbon, this paper attempts to sort out the research framework from three levels: core characteristics, theoretical basis and research methods, respectively. Facing a series of challenges brought by climate change, Blue Carbon research should strengthen the accurate estimations of Blue Carbon sink and its market potential, and explore the reasonable market mechanism and protection mechanism, to respond to realistic demands, solve major concerns and promote new progress in Blue Carbon theory and practice.
Causal association between major depressive disorder and venous thromboembolism: a bidirectional mendelian randomization study
Authors: Li Hong-Yan , Wang Li-Hong , Wang Jing , Wang Yong-Bo , Wang Hai-Shan
Published: June 2024

Purpose

Major depressive disorder (MDD) and venous thromboembolism (VTE) may be linked in observational studies. However, the causal association remains ambiguous. Therefore, this study investigates the causal associations between them.

Methods

We performed a two-sample univariable and multivariable bidirectional Mendelian randomization (MR) analysis to evaluate the associations between MDD and VTE. The summary genetic associations of MDD statistics were obtained from the Psychiatric Genomics Consortium and UK Biobank. Information on VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE) were obtained from the FinnGen Biobank. Inverse-variance weighting was used as the main analysis method. Other methods include weighted median, MR-Egger, Simple mode, and Weighted mode.

Results

Univariable MR analysis revealed no significant associations between MDD and VTE risk (odds ratio (OR): 0.936, 95% confidence interval (CI): 0.736–1.190, p = 0.590); however, after adjusting the potential relevant polymorphisms of body mass index and education, the multivariable MR analysis showed suggestive evidence of association between them (OR: 1.163, 95% CI: 1.004–1.346, p = 0.044). Univariable MR analysis also revealed significant associations between MDD and PE risk (OR: 1.310, 95% CI: 1.073–1.598, p = 0.008), but the association between them was no longer significant in MVMR analysis (p = 0.072). We found no significant causal effects between MDD and DVT risk in univariable or multivariable MR analyses. There was also no clear evidence showing the causal effects between VTE, PE, or DVT and MDD risk.

Conclusion

We provide suggestive genetic evidence to support the causal association between MDD and VTE risk. No causal associations were observed between VTE, PE, or DVT and MDD risk. Further validation of these associations and investigations of potential mechanisms are required.
Advances in analytical techniques for assessing volatile organic compounds in pulse crops: a comprehensive review
Authors: Makhlouf Leila , El Fakhouri Karim , Kemal Seid Ahmed , Aasfar Abderrahim , Meftah Kadmiri Issam , El Bouhssini Mustapha
Published: June 2024

Pulse crops, including beans, peas, chickpeas, and lentils, are vital sources of protein, fiber, and essential nutrients worldwide. They serve not only as staple foods but also as key components of sustainable agricultural practices, contributing to soil fertility through nitrogen fixation and enhancing overall productivity. However, pulse crops face numerous abiotic and biotic stresses mainly insect pest attack and pathogen invasion, which pose significant threats to pulse crops, impacting both production and food security. To overcome these challenges, plants have evolved diverse defense mechanisms, including the emission of specific volatile organic compounds (VOCs). These volatiles play crucial roles in plant communication, protection, and real-time health status indication. Monitoring VOCs offers a promising approach for early detection of pest infestations or pathogen infections, enabling the grower to take early action and decide on the proper control measure to minimize losses. The identification of plant-emitted VOCs requires robust and sensitive analytical techniques such as gas chromatography and mass spectrometry, which are the mainly used techniques for in pulse crops studies. However, traditional methods have limitations, prompting the need for advanced, portable, and real-time detection alternatives, such as gas-sensing technologies. This paper provides a comprehensive review of VOC measuring methods, including extraction, separation, and analytical techniques, focusing on their application in pulse crops. Recent advancements in gas-sensing technologies are also discussed, highlighting their potential in enhancing crop protection and agricultural sustainability.
Coordinated inflammation and immune response transcriptional regulation in breast cancer molecular subtypes
Authors: Velazquez-Caldelas Tadeo Enrique , Zamora-Fuentes Jose Maria , Hernandez-Lemus Enrique
Published: June 2024

Breast cancer, characterized by its complexity and diversity, presents significant challenges in understanding its underlying biology. In this study, we employed gene co-expression network analysis to investigate the gene composition and functional patterns in breast cancer subtypes and normal breast tissue. Our objective was to elucidate the detailed immunological features distinguishing these tumors at the transcriptional level and to explore their implications for diagnosis and treatment. The analysis identified nine distinct gene module clusters, each representing unique transcriptional signatures within breast cancer subtypes and normal tissue. Interestingly, while some clusters exhibited high similarity in gene composition between normal tissue and certain subtypes, others showed lower similarity and shared traits. These clusters provided insights into the immune responses within breast cancer subtypes, revealing diverse immunological functions, including innate and adaptive immune responses. Our findings contribute to a deeper understanding of the molecular mechanisms underlying breast cancer subtypes and highlight their unique characteristics. The immunological signatures identified in this study hold potential implications for diagnostic and therapeutic strategies. Additionally, the network-based approach introduced herein presents a valuable framework for understanding the complexities of other diseases and elucidating their underlying biology.
Current status and future directions for the development of human papillomavirus vaccines
Authors: Wang Rui , Huang Hongpeng , Yu Chulin , Li Xuefeng , Wang Yang , Xie Liangzhi
Published: June 2024

The development of human papillomavirus (HPV) vaccines has made substantive progress, as represented by the approval of five prophylactic vaccines since 2006. Generally, the deployment of prophylactic HPV vaccines is effective in preventing newly acquired infections and incidences of HPV-related malignancies. However, there is still a long way to go regarding the prevention of all HPV infections and the eradication of established HPV infections, as well as the subsequent progression to cancer. Optimizing prophylactic HPV vaccines by incorporating L1 proteins from more HPV subtypes, exploring adjuvants that reinforce cellular immune responses to eradicate HPV-infected cells, and developing therapeutic HPV vaccines used either alone or in combination with other cancer therapeutic modalities might bring about a new era getting closer to the vision to get rid of HPV infection and related diseases. Herein, we summarize strategies for the development of HPV vaccines, both prophylactic and therapeutic, with an emphasis on the selection of antigens and adjuvants, as well as implications for vaccine efficacy based on preclinical studies and clinical trials. Additionally, we outline current cutting-edge insights on formulation strategies, dosing schedules, and age expansion among HPV vaccine recipients, which might play important roles in addressing barriers to vaccine uptake, such as vaccine hesitancy and vaccine availability.
Clinical and translational implications of immunotherapy in sarcomas
Authors: Recine Federica , Vanni Silvia , Bongiovanni Alberto , Fausti Valentina , Mercatali Laura , Miserocchi Giacomo , Liverani Chiara , Pieri Federica , Casadei Roberto , Cavaliere Davide , Falbo Pina Tiziana , Diano Danila , Ibrahim Toni , De Vita Alessandro
Published: June 2024

Immunotherapy has emerged as promising treatment in sarcomas, but the high variability in terms of histology, clinical behavior and response to treatments determines a particular challenge for its role in these neoplasms. Tumor immune microenvironment (TiME) of sarcomas reflects the heterogeneity of these tumors originating from mesenchymal cells and encompassing more than 100 histologies. Advances in the understanding of the complexity of TiME have led to an improvement of the immunotherapeutic responsiveness in sarcomas, that at first showed disappointing results. The proposed immune-classification of sarcomas based on the interaction between immune cell populations and tumor cells showed to have a prognostic and potential predictive role for immunotherapies. Several studies have explored the clinical impact of immune therapies in the management of these histotypes leading to controversial results. The presence of Tumor Infiltrating Lymphocytes (TIL) seems to correlate with an improvement in the survival of patients and with a higher responsiveness to immunotherapy. In this context, it is important to consider that also immune-related genes (IRGs) have been demonstrated to have a key role in tumorigenesis and in the building of tumor immune microenvironment. The IRGs landscape in soft tissue and bone sarcomas is characterized by the connection between several tumor-related genes that can assume a potential prognostic and predictive therapeutic role. In this paper, we reviewed the state of art of the principal immune strategies in the management of sarcomas including their clinical and translational relevance.
Deciphering the molecular landscape of rheumatoid arthritis offers new insights into the stratified treatment for the condition
Authors: Chang Min-Jing , Feng Qi-Fan , Hao Jia-Wei , Zhang Ya-Jing , Zhao Rong , Li Nan , Zhao Yu-Hui , Han Zi-Yi , He Pei-Feng , Wang Cai-Hong
Published: June 2024

Background

For Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments.

Methods

We utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs.

Results

Subtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferon-driving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs.

Conclusions

The findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future.
Current landscape of fecal microbiota transplantation in treating depression
Authors: Zhang Qi , Bi Yajun , Zhang Boyu , Jiang Qiong , Mou Chao Kam , Lei Lelin , Deng Yibo , Li Yutong , Yu Jing , Liu Wei , Zhao Jinzhu
Published: June 2024

Depression, projected to be the predominant contributor to the global disease burden, is a complex condition with diverse symptoms including mood disturbances and cognitive impairments. Traditional treatments such as medication and psychotherapy often fall short, prompting the pursuit of alternative interventions. Recent research has highlighted the significant role of gut microbiota in mental health, influencing emotional and neural regulation. Fecal microbiota transplantation (FMT), the infusion of fecal matter from a healthy donor into the gut of a patient, emerges as a promising strategy to ameliorate depressive symptoms by restoring gut microbial balance. The microbial-gut-brain (MGB) axis represents a critical pathway through which to potentially rectify dysbiosis and modulate neuropsychiatric outcomes. Preclinical studies reveal that FMT can enhance neurochemicals and reduce inflammatory markers, thereby alleviating depressive behaviors. Moreover, FMT has shown promise in clinical settings, improving gastrointestinal symptoms and overall quality of life in patients with depression. The review highlights the role of the gut-brain axis in depression and the need for further research to validate the long-term safety and efficacy of FMT, identify specific therapeutic microbial strains, and develop targeted microbial modulation strategies. Advancing our understanding of FMT could revolutionize depression treatment, shifting the paradigm toward microbiome-targeting therapies.
Multi-omic validation of the cuproptosis-sphingolipid metabolism network: modulating the immune landscape in osteosarcoma
Authors: Li Qingbiao , Fang Jiarui , Liu Kai , Luo Peng , Wang Xiuzhuo
Published: June 2024

Background

The current understanding of the mechanisms by which metal ion metabolism promotes the progression and drug resistance of osteosarcoma remains incomplete. This study aims to elucidate the key roles and mechanisms of genes involved in cuproptosis-related sphingolipid metabolism (cuproptosis-SPGs) in regulating the immune landscape, tumor metastasis, and drug resistance in osteosarcoma cells.

Methods

This study employed multi-omics approaches to assess the impact of cuproptosis-SPGs on the prognosis of osteosarcoma patients. Lasso regression analysis was utilized to construct a prognostic model, while multivariate regression analysis was applied to identify key core genes and generate risk coefficients for these genes, thereby calculating a risk score for each osteosarcoma patient. Patients were then stratified into high-risk and low-risk groups based on their risk scores. The ESTIMATE and CIBERSORT algorithms were used to analyze the level of immune cell infiltration within these risk groups to construct the immune landscape. Single-cell analysis was conducted to provide a more precise depiction of the expression patterns of cuproptosis-SPGs among immune cell subtypes. Finally, experiments on osteosarcoma cells were performed to validate the role of the cuproptosis-sphingolipid signaling network in regulating cell migration and apoptosis.

Results

In this study, seven cuproptosis-SPGs were identified and used to construct a prognostic model for osteosarcoma patients. In addition to predicting survival, the model also demonstrated reliability in forecasting the response to chemotherapy drugs. The results showed that a high cuproptosis-sphingolipid metabolism score was closely associated with reduced CD8 T cell infiltration and indicated poor prognosis in osteosarcoma patients. Cellular functional assays revealed that cuproptosis-SPGs regulated the LC3B/ERK signaling pathway, thereby triggering cell death and impairing migration capabilities in osteosarcoma cells.

Conclusion

The impact of cuproptosis-related sphingolipid metabolism on the survival and migration of osteosarcoma cells, as well as on CD8 T cell infiltration, highlights the potential of targeting copper ion metabolism as a promising strategy for osteosarcoma patients.
Pairing cellular and synaptic dynamics into building blocks of rhythmic neural circuits. A tutorial
Authors: Scully James , Bourahmah Jassem , Bloom David , Shilnikov Andrey L.
Published: June 2024

In this study we focus on two subnetworks common in the circuitry of swim central pattern generators (CPGs) in the sea slugs, Melibe leonina and Dendronotus iris and show that they are independently capable of stably producing emergent network bursting. This observation raises the question of whether the coordination of redundant bursting mechanisms plays a role in the generation of rhythm and its regulation in the given swim CPGs. To address this question, we investigate two pairwise rhythm-generating networks and examine the properties of their fundamental components: cellular and synaptic, which are crucial for proper network assembly and its stable function. We perform a slow-fast decomposition analysis of cellular dynamics and highlight its significant bifurcations occurring in isolated and coupled neurons. A novel model for slow synapses with high filtering efficiency and temporal delay is also introduced and examined. Our findings demonstrate the existence of two modes of oscillation in bicellular rhythm-generating networks with network hysteresis: i) a half-center oscillator and ii) an excitatory-inhibitory pair. These 2-cell networks offer potential as common building blocks combined in modular organization of larger neural circuits preserving robust network hysteresis.
Cerebral cortex functional reorganization in preschool children with congenital sensorineural hearing loss: a resting-state fMRI study
Authors: Yin Yi , Lyu Xinyue , Zhou Jian , Yu Kunlin , Huang Mingming , Shen Guiquan , Hao Cheng , Wang Zhengfu , Yu Hui , Gao Bo
Published: June 2024

Purpose

How cortical functional reorganization occurs after hearing loss in preschool children with congenital sensorineural hearing loss (CSNHL) is poorly understood. Therefore, we used resting-state functional MRI (rs-fMRI) to explore the characteristics of cortical reorganization in these patents.

Methods

Sixty-three preschool children with CSNHL and 32 healthy controls (HCs) were recruited, and the Categories of Auditory Performance (CAP) scores were determined at the 6-month follow-up after cochlear implantation (CI). First, rs-fMRI data were preprocessed, and amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were calculated. Second, whole-brain functional connectivity (FC) analysis was performed using bilateral primary auditory cortex as seed points. Finally, Spearman correlation analysis was performed between the differential ALFF, ReHo and FC values and the CAP score.

Results

ALFF analysis showed that preschool children with CSNHL had lower ALFF values in the bilateral prefrontal cortex and superior temporal gyrus than HCs, but higher ALFF values in the bilateral thalamus and calcarine gyrus. And correlation analysis showed that some abnormal brain regions were weak negatively correlated with CAP score (p < 0.05). The ReHo values in the bilateral superior temporal gyrus, part of the prefrontal cortex and left insular gyrus were lower, whereas ReHo values in the bilateral thalamus, right caudate nucleus and right precentral gyrus were higher, in children with CSNHL than HCs. However, there was no correlation between ReHo values and the CAP scores (p < 0.05). Using primary auditory cortex (PAC) as seed-based FC further analysis revealed enhanced FC in the visual cortex, proprioceptive cortex and motor cortex. And there were weak negative correlations between the FC values in the bilateral superior temporal gyrus, occipital lobe, left postcentral gyrus and right thalamus were weakly negatively correlated and the CAP score (p < 0.05).

Conclusion

After auditory deprivation in preschool children with CSNHL, the local functions of auditory cortex, visual cortex, prefrontal cortex and somatic motor cortex are changed, and the prefrontal cortex plays a regulatory role in this process. There is functional reorganization or compensation between children’s hearing and these areas, which may not be conducive to auditory language recovery after CI in deaf children.
qNMR in natural products: practical approaches. What nobody tells you before starting your qNMR study!
Authors: Ravaglia Luciana Marcal , de Oliveira Paola Dias , Holzgrabe Ulrike , Alcantara Glaucia Braz
Published: June 2024

NMR (Nuclear Magnetic Resonance) spectroscopy is a well-established technique for elucidating the structure and composition of Natural Products (NP). However, while NMR spectra offer qualitative insights, there is often a growing demand within the NP research community for quantitative analysis using NMR techniques. Unfortunately, this demand is sometimes met with misconceptions and lacks the methodological rigor typically associated with analytical procedures, particularly concerning validation and mandatory adjustments of quantitative NMR (qNMR) parameters. Therefore, this minireview highlights the practical approaches concerning preparation and validation for qNMR analyses of plant extracts. Specifically, we provide a concise protocol detailing experimental settings crucial for ensuring the accuracy and reliability of quantitative measurements. It is noteworthy that such guidance is often absent in existing literature, and our minireview wants to bridge this gap by offering clear methodological recommendations.
Abrupt elevation of tumor marker levels in a huge splenic epidermoid cyst, a case report
Authors: Cai Hao , Hei Zhenyu , Liu Guanghua , Zhao Feng , Wang Chunfeng , Guan Wenbin , Ren Gang , Zhou Qing , Dong Yi , Wang Ying , Gong Wei , Chen Litian
Published: June 2024

Epidermoid cyst of the spleen is a rare disease, and relatively few cases were reported by literatures. Most published case reports provided inadequate information on the impact of splenic epidermoid cyst on tumor markers. A 32-year-old woman with a giant splenic epidermoid cyst was reported, for whom the serum concentration of a collection of tumor markers (CA19–9, CEA, CA125, CA242, and CA50) increased abruptly accompanied by left upper abdominal pain for 5 days. After comprehensive preoperative examination and multidisciplinary team discussion, we ruled out any concurrent malignancy and a laparoscopic total splenectomy was performed, during which the splenic cyst spontaneously ruptured unexpectedly. After surgery, the elevated serum tumor marker levels decreased sharply until reaching normal range 3 months later. Learning from the case, we conclude that interval monitoring of serum tumor markers is of critical value for patients with splenic epidermoid cyst. Abrupt elevation of tumor marker levels and abdominal pain may serve as signs of cyst rupture, which is strongly indicative of surgical intervention as soon as possible. Total removal of the splenic cyst is strongly suggested considering the recurrence and malignant potential of the splenic epidermoid cyst.
Ameliorative action of “daitongxiao” against hyperuricemia includes the “uric acid transporter group”
Authors: Zheng Lijie , Bai Yuanmei , Wan Yan , Liu Feifan , Xie Yuhuan , He Jinglin , Guo Peixin
Published: June 2024

This study aimed to investigate the potential mechanisms involved in the therapeutic effects of daitongxiao (DTX) on hyperuricemia (HUA). DTX was administered to two animal models of HUA via gavage feeding: HUA quail model (a uricotelic animal with urate oxidase deficiency), treated continuously for 35 days post-HUA induction, and HUA rats (an animal with active urate oxidase), treated continuously for 28 days post-HUA induction. HUA was induced in quail by administering a solution of sterile dry yeast powder via gavage feeding, while in rats, it was induced by intragastric gavage feeding of a solution of adenine and ethambutol hydrochloride. DTX improved overall health; increased bodyweight; reduced renal index, serum urate levels, serum xanthine oxidase activity, blood urea nitrogen, and creatinine; and enhanced urinary and fecal uric acid (UA) excretion in these two animal models. The results of hematoxylin and eosin and hexamine silver staining of kidney sections revealed that DTX significantly mitigated HUA-induced renal structural damage and inflammatory response. The results of quantitative real-time polymerase chain reaction, Western blotting, and immunofluorescence analyses revealed that DTX downregulated the renal expression levels of glucose transporter 9 (GLUT9) and upregulated the renal expression levels of organic anion transporters (OAT1 and OAT3) in both HUA models. Thus, the findings of this study suggest that DTX suppresses the progression of HUA by modulating the expression of the UA transporter group members.
Influence of sodium/glucose cotransporter-2 inhibitors on the incidence of acute kidney injury: a meta-analysis
Authors: Wang Qian , Yu Jianmin , Deng Weizhu , Liu Chao , Yang Jian , Li Yaqing , Cai Guangyan , Chen Xiangmei , Dong Zheyi
Published: June 2024

Background

Sodium/glucose cotransporter-2 inhibitors (SGLT2i) are associated with cardiovascular benefits. The aim of this systematic review and meta-analysis is to summarize the influence of SGLT2i on the incidence of acute kidney injury (AKI), and to ascertain whether it is affected by confounding variables such as age, baseline renal function and concurrent use of renin-angiotensin-aldosterone system inhibitors (RAASi) or mineralocorticoid receptor antagonists (MRA).

Methods

PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials comparing the influence of SGLT2i versus placebo/blank treatment on AKI in the adult population. A fixed-effect model was used if the heterogeneity was not significant; otherwise, a randomized-effect model was used.

Results

Eighteen studies comprising 98,989 patients were included. Compared with placebo/blank treatment, treatment with SGLT2i significantly reduced the risk of AKI (risk ratio [RR]: 0.78, 95% confidence interval [CI]: 0.71 to 0.84, p < 0.001; I2 = 0%). Subgroup analysis suggested consistent results in patients with diabetes, chronic kidney disease, and heart failure (for subgroup difference, p = 0.32). Finally, univariate meta-regression suggested that the influence of SGLT2i on the risk of AKI was not significantly modified by variables such as age (coefficient: 0.011, p = 0.39), baseline estimated glomerular filtration rate (coefficient: −0.0042, p = 0.13) or concomitant use of RAASi (coefficient: 0.0041, p = 0.49) or MRA (coefficient: −0.0020, p = 0.34).

Conclusion

SGLT2i may be effective in reducing the risk of AKI, and the effect might not be modified by age, baseline renal function and concurrent use of RAASi or MRA.
The effect of remimazolam-based total intravenous anesthesia versus sevoflurane-based inhalation anesthesia on emergence delirium in children undergoing tonsillectomy and adenoidectomy: study protocol for a prospective randomized controlled trial
Authors: Ma Hong-Yu , Cai Yu-Hang , Zhong John Wei , Chen Jia , Wang Zhen , Lin Chao-Yi , Wang Qiao-Qiao , Liu Hua-Cheng
Published: June 2024

Background: Remimazolam, a new ultrashort-acting benzodiazepine, is becoming increasingly applied in general anesthesia. This study is designed to investigate the effect of remimazolam-based total intravenous anesthesia and sevoflurane-based inhalation anesthesia on emergence delirium in pediatric tonsillectomy and adenoidectomy.

Methods and analysis: This is a monocentric, prospective, randomized, double-blind clinical trial. A total of 90 pediatric patients will be randomized to receive remimazolam-based total intravenous anesthesia (remimazolam group, n = 45) or sevoflurane-based inhalation anesthesia (sevoflurane group, n = 45). The primary outcome will be the incidence of emergence delirium, which will be evaluated using the Pediatric Anesthesia Emergence Delirium (PAED) scale. The secondary outcomes include the extubation time, recovery time, behavior change using the post-hospitalization behavior questionnaire for ambulatory surgery (PHBQ-AS), and adverse events.

Ethics and dissemination: This study has been approved by the Institutional Review Board (IRB) of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University (2023-K-262-02).

Clinical trial registration:ClinicalTrials.gov, identifier NCT06214117.