bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment and application of drug utilization evaluation applying the weighted TOPSIS method: A study based on real-world data of tislelizumab
Authors: Li Yang , Chen Qianxi , Zhu Tao , Lu Shaohuan , Liang Canhua , Wang Guangzhao , Wu Xuefeng , Meng Guangyi
Published: March 2024

BACKGROUND: How to comprehensively evaluate the rationality of drug use is a challenging issue. OBJECTIVE: To establish the evaluation index of the effective use of tislelizumab, so as to ensure its higher rationality and normalization in clinical application. METHODS: Based on the indications, drug instructions, and relevant guidelines of the National Basic Medical Insurance Restriction Catalogue, a retrospective analysis and evaluation of 286 cases of using tislelizumab injection in our hospital from January to December 2022 were conducted using the weighted technique for order of preference by similarity to ideal solution (TOPSIS) method. RESULTS: Among the 286 medical records evaluated, the main irrational manifestations were inappropriate indications (90 cases, 31.47%), auxiliary examination and laboratory examination did not meet the minimum requirements of combination chemotherapy drugs (40 cases, 13.99%), the drug course was not standard (39 cases, 13.64%). Among the included cases, 57.34% were reasonable cases (Ci⩾ 0.8), 10.84% were basic reasonable cases (0.6 ⩽Ci< 0.8), and 31.82% were unreasonable cases (Ci< 0.6). CONCLUSION: The TOPSIS method, with its attribute hierarchical model (AHM)-weighted approach, can be employed as the rational assessment technique for the injection of tislelizumab. The clinical application of tislelizumab in our hospital is still insufficient, which needs to be further improved management.
Effect of orthodontics combined with fibre-reinforced composite resin-bonded fixed partial denture on anterior dentition defects with minimal vertical intermaxillary space
Authors: Han Shi-Lei , Li Na
Published: March 2024

BACKGROUND: Prosthodontics are often performed to treat patients with malocclusion and dentition defects. However, single prosthodontics cannot properly correct the disharmony of teeth, dental arch and other parts affected by malocclusion, and some patients may have difficulty in recovering the occlusal function due to poor prosthodontics. OBJECTIVE: This study aims to investigate the effect of orthodontics combined with fibre-reinforced composite resin-bonded fixed partial denture (FRC-RBFPD) on anterior dentition defects with minimal vertical intermaxillary space. METHODS: Sixty-two patients with anterior dentition defects with minimal vertical mandibular space admitted to our hospital between March 2021 and May 2023 were enrolled in this study. The participants were divided into the observation group (31 cases) and the control group (31 cases), according to the treatment plan. The control group was treated with traditional therapy, and the observation group was treated with orthodontic combined FRC-RBFPD therapy. Periodontal conditions (periodontal pocket depth [PD], the plaque index [PLI], the sulcus bleeding index [SBI]), levels of inflammatory factors in gingival crevicular fluid (high mobility group box 1 [HMGB1]), myeloid cell triggering receptor-1 (TREM-1), monocyte chemoattractant protein-1 (MCP-1), pain (visual analogue scale [VAS]), the clinical response rate and the incidence of adverse reactions were collected and compared. RESULTS: After 1, 3, 5 and 9 months following treatment, the scores of the PD, PLI, SBI, HMGB1, VAS, TREM-1 and MCP-1 in the observation group were found to be lower than those in the control group (FPD treatment= 352.532, FPLI score treatment= 112.341, FSBI score treatment= 79.479, FVAS score treatment= 96.132, FHMGB1 treatment= 52.532, FTREM-1 score treatment= 64.593, FMCP-1 score treatment= 53.582, and they were all statistically significant P< 0.05). There was a statistically significant difference in the response rate between the two groups (97.77% vs. 80.65%, χ2= 4.026, P= 0.045). No statistically significant difference was observed in the incidence of adverse reactions between the two groups (6.45% vs. 16.13%, χ2= 1.449, P= 0.229). CONCLUSION: Orthodontics combined with FRC-RBFPD shows an ideal restorative effect on patients with anterior dentition defects and minimal vertical intermaxillary space.
Investigating the effect of hot and cold polyurethane foam on reducing whole body vibration of forklift operators
Authors: Hajizadeh Roohalah , Ghiasvand Fatemeh , Azimi Pirsaraei Seyed Reza , Khani Fouzia , Feiz-Arefi Maryam , Beheshti Mohammad Hosein
Published: March 2024

BACKGROUND: Vibration is one of the harmful factors for forklift drivers. The use of non- standard seats and not paying attention to how the seats are maintained can be affected by the amount of vibration transmitted to the person. OBJECTIVE: This study investigates the amount of vibration transmitted from the forklift and the effect of different types of polyurethane foam in reducing the vibration transmitted from the forklift seat. METHODS: This descriptive-analytical study was performed on 38 forklifts in 4 diesel models with the same weight class. The amount of vibration transmitted from forklift seats according to ISO2631 standard, taking into account the effect of various factors such as foam type (hot and cold), thickness (6–12 cm), load and year Function was measured. The amount of vibration caused by the forklift on the seat and under the seat was evaluated using ISO7096 standard. RESULTS: The average total vibration of the whole body in all foams in no-load mode is more than with load. The transmission vibration of cold polyurethane foam is less than that of hot polyurethane foam. With increasing thickness, the efficiency of cold polyurethane foam increases by 12 cm and in the loaded state 40.63% and in the unloaded state 49.58% in reducing the vibration transmitted to drivers. CONCLUSION: The results of this study show that cold foam has better effectiveness and efficiency than hot polyurethane foam. Also, the thicker the foam, the less vibration is transmitted to the driver.
Understanding Theosemiotic: Concept and its Position
Authors: Taqiyuddin Muhammad
Published: March 2024

This manuscript explores the concept of theosemiotics, a term that signifies the intersection of semiotic theory and theological interpretation. Originating from the work of Michael L. Raposa and grounded in Charles Sander Peirce’s semiotic framework, theosemiotics is presented as a means to understand religious semiotics, particularly within Islamic and Christian contexts. Through a detailed examination of its historical development, theoretical underpinnings, and potential for bridging science and religion, the manuscript highlights theosemiotics as a promising area for academic research. It argues for the relevance of theological semiotics in contemporary discussions on the integration of religious perspectives with scientific inquiry, offering a comprehensive analysis of signs in the divine context. This study contributes to the broader discourse on the role of religion in the public sphere and the ongoing dialogue between faith and reason.
Teoria de geração de energia através da separação das forças
Authors: Caetano Carlos Manuel Silva
Published: March 2024

Estudo para aumentar a capacidade de produção de energia renovável. Será a demonstração de um movimento mecânico que na sua elaboração executa um dinamismo de aproveitar as forças de uma direção e as forças aerodinâmicas noutras todas as direções, mas na continuação da direção da força original há uma particularidade. As forças resultantes podem efetuar trabalho. Com esta teoria poderá servir para desenvolver mecanismos como, por exemplo, para produzir energia e proteção de infraestruturas como navios, portos, zonas costeiras, veículos na alta atmosfera, etc. Será que estas teorias funcionam exatamente na realidade? Se não funcionar cem por cento, que correções serão necessárias? Quantos testes para se obter resultados satisfatórios? Devem ser feitas muitas simulações. Para produzir energia poderá ser da força do vento, a água como as ondas marítimas, corrente de água dos rios e vento solar no espaço. As representações em diversos desenhos prometem um bom desempenho mecânico. Com adaptações mecânicas poderá ser um mecanismo de grandes dimensões. Poderá ser equipamentos grandes que poderão produzir muita energia.
Neem (Azadirachta indica A. Juss) leaves as growth promoter in lambs’ diets
Authors: MARTÍNEZ AISPURO JOSÉ ALFREDO , CORDERO MORA JOSÉ LUIS , MARTINEZ GARCÍA JOSE ANTONIO , MENDOZA MARTÍNEZ GERMAN DAVID , SANCHEZ TORRES ESQUEDA MARIA TERESA , FIGUEROA VELASCO JOSÉ LUIS
Published: March 2024

Objective: To evaluate the dietary inclusion of neem leaves on the productive and biochemical performance of fattening lambs.
Design/methodology: Forty male lambs were assigned according to a completely randomized design. Treatments consisted of dietary inclusion of neem at 0.0, 2.5, 5.0, and 7.5 g kg-1 DM for 35 days. 
Results: The inclusion of neem leaf in the diet did not affect the productive performance (P>0.05), while protein and energy metabolites were modified (P≤0.05).
Limitations on study/implications: The bioactive compounds present in neem modified the metabolites related to protein and energy metabolism, although these changes did not reflect improvements in the productive performance.
Conclusions: The inclusion of dietary neem (2.5-7.5 g kg-1) has no effect on the productive performance, although it does modify some energy and protein metabolites.
Competitiveness of mexican pecans [Carya illinoinensis (Wangenh) K.Koch] and almonds [Prunus dulcis (Mill.) D.A.Webb] in the international market
Authors: Serrano López Abisai , Valdivia-Alcalá Ramón , Garay-Jácome Ángeles S. , Hernández-Ortiz Juan , Contreras-Castillo José M.
Published: March 2024

Objective: Measurement and analysis of the competitiveness of Mexican pecan nuts (Carya illinoinensis) and almonds (Prunus dulcis) in the international market with respect to the United States, during the period 2012-2021.
Design/Methodology/Approach: The Revealed Comparative Advantage Index was used to identify the factors that influence its performance and propose strategies to improve its market position.
Results: Mexican pecans to the United States are competitive (0.68 to 0.94) over the years. The IVCR of Mexican pecans to the United States remain consistently above zero (0.68 to 0.94) over the years.
Study Limitations/Implications: Information on the trade of Mexican pecan nuts and almonds may be limited, making it difficult to calculate the IVCR.
Findings/Conclusions: Mexican pecan nut shows favorable competitiveness in the U.S. market while almond its competitiveness is limited, it is not competitive with respect to the market.
Field identification of Huanglongbing (HLB) and its management alternatives
Authors: Martínez-Netro Karen J. , Martínez-Padrón Hadassa Y , Segura-Martínez Ma. T.J. , Paredes-Sánchez Francisco A. , Herrera-Mayorga Verónica , Rodríguez-Herrera Raúl , Osorio-Hernández Eduardo
Published: March 2024

EObjective: The objective of this investigation is to identify huanglongbing (HLB) in the field and know their control altenatives. 
Design/methodology/approach: Was investigated the introduction of the phytopathogen Candidatus Liberibacter, symptoms and control of HLB. The generally observed symptoms of this disease are irregular yellowing in the leaves and reversed ripening on the fruit. 
Results: According to various authors, an integrated control of the disease must be carried out, such as pest control, production of seedlings in certified nurseries, a suitable nutrition management and working together with educational and research institutions. 
Limitations on study/implications: HLB or citrus greening is the most devastating disease of citrus trees which has caused millions of dollars in losses worldwide. However, although there are several research, there is still no established cure. 
Findings/conclusions: Research such as that carried out by geneticist Hailing Jin at the University of California Riverside can give hope for the cure or control of this disease, however, there are limitations to this product since it is not yet commercialized
Antibiosis of Salicylic acid Pre-Hardening Treatments of Cowpea on Development of Pod Sucking Bug, Clavigralla tomentosicollis Stal. (Hemiptera: Coreidae)
Authors: Audi Auwalu Hassan , Mukhtar F. B.
Published: March 2024

to control physiological interactions of Phytophagous insects The experiment was conducted at the University Research farm, Faculty of Agriculture Bayero University, Kano (11°58 ‘N, 8° 25’ E and 457m above sea level) to evaluate the effect of SA-treatment on Development of Pod sucking bug of cowpea. Four different cowpea varieties (IT97K-1069-6, IT98K-205-8, IT89KD-288 and Dan’ila) pre-hardened with Salicylic acid were established in various replicated field cages in completely randomized design. Five-pairs each of fresh bugs were introduced into the various cages. These were allowed for 2-weeks to mate and oviposit after which all adult insects are removed. Introduced insects showed variable developmental response to the different Pre-hardened cowpea varieties in SA hormones (P<0.001). Interactions of treatments and varieties was also found significant (P<0.001).Cowpea seeds treated with lower (5ppm) concentrations of SA show greater deleterious effects on the development of the pod bugs than the higher (10 & 20ppm) concentrations and the controls (Distilled water & Untreated seeds). Of the four Cowpea varieties screened, IT97K-1069-6 and IT89KD-288 of 5ppm SA-treatments show higher antibiosis on development of C. tommentosicollis, resulting to low oviposition (41.33 and 45.67), higher percentage nymphal mortalities (71.59% and 77.24%) and mean unhatched eggs of 27.33 and 32.00 respectively, with smaller adults bugs (3.55mg and 3.27mg) at emergence. Phytochemical screening of the treatments using GC-MS analysis showed high concentrations of cumene, eugenol and sesquiterpenes in the tolerant varieties. These relations should be explored extensively toward sustainable plant protection.
Manejo do enfermeiro na manutenção do potencial doador de órgãos na unidade de terapia intensiva: uma revisão integrativa
Authors: Guedes Michele Ribeiro da Silva , Galindo Ana Raquel Ferreira , Marques Bárbara  Clarice dos Santos , Buarque Bruna de Souza , Leite Emanuelly Falcão de Sousa , Barbosa Hosana dos Santos , Bezerra João Alberto Soares , Silva Márcia Maria de Lima , Cavalcanti Marlon Chaves , Silva Roberto Bezerra da , Bandeira Tayanne Laiz da Silva , Silva Whâniza Sulana Costa
Published: March 2024

A importância da atuação do enfermeiro de forma adequada diante do paciente com morte encefálica é crucial para a viabilização e o  aumento do número de  transplantes. A assistência prestada em tempo e com rigoroso conhecimento técnico científico ao paciente determinará o sucesso ou não da doação. Este estudo pretende realizar uma revisão integrativa da literatura com busca nas bases de dados BVS, Medline, Lilacs e BDENF, no período de agosto a  dezembro de 2022. Critérios de inclusão: estudos com texto na íntegra, publicados nos idiomas português e inglês. Excluídos: textos da literatura cinzenta. Descritores utilizados: obtenção de tecidos e órgãos, morte encefálica, enfermagem. A manutenção do potencial doador é parte do  processo de doação de órgãos, essencial para viabilizar os órgãos para o transplante. O profissional de enfermagem necessita obter conhecimento sobre as alterações fisiológicas que acometem o paciente portador de morte encefálica a fim de ajustar possiveis alterações.  O cenário de doação de órgãos e transplantes ainda possui um longo caminho em sua evolução, necessitando de profissionais capacitados para atuar nas diversas partes do processo, sendo a manutenção do paciente doador uma das partes mais importantes  para que se obtenha sucesso do  transplante de forma eficiente e assim promovendo enxertos de qualidade aos receptores.
New coronavirus infection (COVID-19) and the nosological structure of patients of the rheumatological department. A glance look from the region
Authors:   Yaroslavl State Medical University of the Ministry of Health of the Russian Federation, Yaroslavl, Russia, Rechkina E.V. , Korshunov N.I. ,   Yaroslavl State Medical University of the Ministry of Health of the Russian Federation, Yaroslavl, Russia, Baranov A.A. ,   Yaroslavl State Medical University of the Ministry of Health of the Russian Federation, Yaroslavl, Russia, Konovalov K.M. ,   Yaroslavl State Medical University of the Ministry of Health of the Russian Federation, Yaroslavl, Russia, Malygina E.A. ,   Yaroslavl State Medical University of the Ministry of Health of the Russian Federation, Yaroslavl, Russia
Published: March 2024

Based on the analysis of 670 archival patients' case histories of the disease, patients discharges in 2021 from the rheumatological department (there are excluded cases of repeated short-term hospitalizations in order to conduct supporting therapy of genetically engineering biological drugs), the question of the connection of rheumatic pathology with coronaviral infection and its influence on the formation of the characteristics of clinical clinicals forms of this pathology. Coronavirus infection, which occurred in the period of 6 months before hospitalization, is registered in every tenth (76–11.3 %). Three groups are highlighted: I. Patients with the diagnosis of Covid diagnosed/verified in the department and who later transferred to the specialized infectious department – 18 people (2.7 %). II. Patients who have clinical features of the disease can be interpreted as part of the so -called post-covid syndrome – 35 people (5.2 %). A clear chronological relationship of post-covid asthenia and other symptoms with subsequent (after 4 weeks) events make the role of the virus in the induction of this pathology undoubted. III. Patients with a previously established rheumatic diagnosis, and the exacerbation of a previously diagnosed disease was undoubtedly induced by coronavirus infection – 23 people (3.4 %) among those patients. The relationship of the development and exacerbation of chronic rheumatic pathology with coronavirus is actually much more often than the numbers cited in this study, but many cases of light infection were not recorded as COVID. Post-covid syndromes in rheumatology, developing at different times from the beginning of the infection, from the so called long-covid is up to six months, have a wide range of clinical manifestations. It can be assumed that the most characteristic feature of patients with post-covid syndromes who find themselves in the hospital is their uncertainty in terms of specification of the nosological form. It is significant that in 80 % of patients in whom the clinical features can be considered as part of the post-covid syndrome, such “transitional” diagnoses as inflammatory arthropathy, undifferentiated or mixed connective tissue syndrome, RS3PE syndrome and others, and only less than a smaller part of the patients examined had more outlined signs of a specific rheumatic disease.
The blockade of the shoulder plexus by axillary access. Literature review
Authors:   G. R. Derzhavin Tambov State University, Medical InstituteT, ambov, Russia, Yamshchikov O. N. , Marchenko A.P. ,   G. R. Derzhavin Tambov State University, Medical Institute, Tambov, Russia, Emelyanov S. A. ,   G. R. Derzhavin Tambov State University, Medical Institute, Tambov, Russia, Ivanova O.D. ,   G. R. Derzhavin Tambov State University, Medical Institute, Tambov, Russia, Ignatova S.A. ,   G. R. Derzhavin Tambov State University, Medical Institute, Tambov, Russia, Marchenko N.A. ,   G. R. Derzhavin Tambov State University, Medical Institute, Tambov, Russia
Published: March 2024

The main tasks of an anesthesiologist during the anesthesiological support of surgical interventions are the maximum possible protection of the patient from pain with minimal effect on homeostasis, creating comfortable conditions for the work of operating surgeons. These requirements fully comply with regional paintering methods, especially during operations on the upper limb, when the anesthesiologist has a choice: to perform general anesthesia or blockade of the shoulder plexus. The regional blockade will fully ensure adequate analgesia, hyporeflexia and relaxation in the operation zone. To increase the efficiency and safety of regional blockade, ultrasonic navigation and neuromuscular stimulation are used. One of the safest and easy-to-perform is axillar access. Objective. Summarize and present modern information about the regional blockade of the shoulder plexus from axillary access. Material and methods. During the writing of the article on regional methods of upper limb anesthesia, in particular on axillary access, a literature from open electronic scientific databases of Pubmed, the US National Electronic Medical Library and Databases of the Russian Scientific Electronic Library Elibary was analyzed. Results. An analysis of domestic and foreign literature dedicated to the blockade of the shoulder plexus with axillary access was carried out. The article discusses options for the location of the nerve trunks of the shoulder plexus in the axillary region, the technique of performing the axillar blockade, indications and possible complications. Conclusions. The priority when choosing access when blocking the shoulder plexus is to ensure the safety and efficiency of anesthesia, especially in high-risk patients. Axillar access using sonoscopy and neuromuscular stimulation fully complies with these requirements.
Double Immunohistochemical Labelling of PRAME and Melan A in Slow Mohs Biopsy Margin Assessment of Lentigo Maligna and Lentigo Maligna Melanoma
Authors: Salih R. , Ismail F. , Orchard G. E.
Published: March 2024

Introduction: Lentigo maligna (LM) and lentigo maligna melanoma (LMM) predominantly affect the head and neck areas in elderly patients, presenting as challenging ill-defined pigmented lesions with indistinct borders. Surgical margin determination for complete removal remains intricate due to these characteristics. Morphological examination of surgical margins is the key form of determining successful treatment in LM/LMM and underpin the greater margin control provided through the Slow Mohs micrographic surgery (SMMS) approach. Recent assessments have explored the use of immunohistochemistry (IHC) markers, such as Preferentially Expressed Antigen in Melanoma (PRAME), to aid in LM/LMM and margin evaluation, leveraging the selectivity of PRAME labelling in malignant melanocytic neoplasms.

Methods: A Novel double-labelling (DL) method incorporating both PRAME and MelanA IHC was employed to further maximise the clinical applicability of PRAME in the assessment of LM/LMM in SMMS biopsies. The evaluation involved 51 samples, comparing the results of the novel DL with respective single-labelling (SL) IHC slides.

Results: The findings demonstrated a significant agreement of 96.1% between the DL method and SL slides across the tested samples. The benchmark PRAME SL exhibited a sensitivity of 91.3% in the SMMS specimens and 67.9% in histologically confirmed positive margins.

Discussion: This study highlights the utility of PRAME IHC and by extension PRAME DL as an adjunctive tool in the assessment of melanocytic tumours within staged excision margins in SMMS samples.
Image based analytical approaches for study of particulate matter (PM) in air
Authors: Tiwari Ankesh , Pandey Mohineeta , Tirkey Astha , Tiwari Aradhana , Dubey Rashmi , Pandey Sudhir Kumar
Published: March 2024

Particulate matter (PM) stands as a predominant pollutant in developing countries, demanding effective source identification and remediation strategies. This review centers on the scanning electron microscopy (SEM) image-based methodology for PM analysis, particularly emphasizing the passive technique of utilizing plant leaves for PM capture. The SEM-image-based approach serves as a powerful tool for unraveling the morphological characteristics of PM, crucial for source identification. Additionally, SEM, when equipped with energy dispersive spectroscopy (EDS), enables chemical and mineralogical characterization, providing insights into the origin of PM. The first part of the review describes the plant as the best bio-sampler for PM. In this context, removal of PM from the environment through plant-based interventions is described. Subsequently, the application of SEM for size-based analysis using ImageJ and morphological analysis for source identification of PM is detailed. Following this, the PM chemical and mineralogical composition for source identification are described based on EDS analysis. Image-based techniques play a pivotal role in selecting the most effective plant species for PM removal from the air. The review comprehensively outlines the morphological, chemical, and mineralogical attributes utilized for PM source identification and their subsequent remediation by plants. Finally, the benefits of SEM-image-based techniques for PM analysis are elucidated. This review offers a holistic understanding of the SEM-EDS and plant-based approach, presenting a promising avenue for addressing PM pollution and enhancing environmental quality.
Local carbachol application induces oral microvascular recruitment and improves gastric tissue oxygenation during hemorrhagic shock in dogs
Authors: Hof Stefan , Lingens Lara , Michels Marius , Marcus Carsten , Kuebart Anne , Herminghaus Anna , Bauer Inge , Picker Olaf , Truse Richard , Vollmer Christian
Published: March 2024

Introduction

Hemorrhagic shock is characterized by derangements of the gastrointestinal microcirculation. Topical therapy with nitroglycerine or iloprost improves gastric tissue oxygenation but not regional perfusion, probably due to precapillary adrenergic innervation. Therefore, this study was designed to investigate the local effect of the parasympathomimetic carbachol alone and in combination with either nitroglycerine or iloprost on gastric and oral microcirculation during hemorrhagic shock.

Methods

In a cross-over design five female foxhounds were repeatedly randomized into six experimental groups. Carbachol, or carbachol in combination with either nitroglycerine or iloprost were applied topically to the oral and gastric mucosa. Saline, nitroglycerine, or iloprost application alone served as control groups. Then, a fixed-volume hemorrhage was induced by arterial blood withdrawal followed by blood retransfusion after 1h of shock. Gastric and oral microcirculation was determined using reflectance spectrophotometry and laser Doppler flowmetry. Oral microcirculation was visualized with videomicroscopy. Statistics: 2-way-ANOVA for repeated measurements and Bonferroni post-hoc analysis (mean ± SEM; p < 0.05).

Results

The induction of hemorrhage led to a decrease of gastric and oral tissue oxygenation, that was ameliorated by local carbachol and nitroglycerine application at the gastric mucosa. The sole use of local iloprost did not improve gastric tissue oxygenation but could be supplemented by local carbachol treatment. Adding carbachol to nitroglycerine did not further increase gastric tissue oxygenation. Gastric microvascular blood flow remained unchanged in all experimental groups. Oral microvascular blood flow, microvascular flow index and total vessel density decreased during shock. Local carbachol supply improved oral vessel density during shock and oral microvascular flow index in the late course of hemorrhage.

Conclusion

The specific effect of shifting the autonomous balance by local carbachol treatment on microcirculatory variables varies between parts of the gastrointestinal tract. Contrary to our expectations, the improvement of gastric tissue oxygenation by local carbachol or nitroglycerine application was not related to increased microvascular perfusion. When carbachol is used in combination with local vasodilators, the additional effect on gastric tissue oxygenation depends on the specific drug combination. Therefore, modulation of tissue oxygen consumption, mitochondrial function or alterations in regional blood flow distribution should be investigated.
Unveiling spatial complexity in solid tumor immune microenvironments through multiplexed imaging
Authors: Scheuermann Sophia , Kristmann Beate , Engelmann Fabienne , Nuernbergk Alice , Scheuermann David , Koloseus Marie , Abed Tayeb , Solass Wiebke , Seitz Christian M.
Published: March 2024

Deciphering cellular components and the spatial interaction network of the tumor immune microenvironment (TIME) of solid tumors is pivotal for understanding biologically relevant cross-talks and, ultimately, advancing therapies. Multiplexed tissue imaging provides a powerful tool to elucidate spatial complexity in a holistic manner. We established and cross-validated a comprehensive immunophenotyping panel comprising over 121 markers for multiplexed tissue imaging using MACSima™ imaging cyclic staining (MICS) alongside an end-to-end analysis workflow. Applying this panel and workflow to primary cancer tissues, we characterized tumor heterogeneity, investigated potential therapeutical targets, conducted in-depth profiling of cell types and states, sub-phenotyped T cells within the TIME, and scrutinized cellular neighborhoods of diverse T cell subsets. Our findings highlight the advantage of spatial profiling, revealing immunosuppressive molecular signatures of tumor-associated myeloid cells interacting with neighboring exhausted, PD1high T cells in the TIME of hepatocellular carcinoma (HCC). This study establishes a robust framework for spatial exploration of TIMEs in solid tumors and underscores the potency of multiplexed tissue imaging and ultra-deep cell phenotyping in unraveling clinically relevant tumor components.
Light on Alzheimer’s disease: from basic insights to preclinical studies
Authors: Mi Jie , Liu Chao , Chen Honglei , Qian Yan , Zhu Jingyi , Zhang Yachao , Liang Yizhi , Wang Lidai , Ta Dean
Published: March 2024

Alzheimer’s disease (AD), referring to a gradual deterioration in cognitive function, including memory loss and impaired thinking skills, has emerged as a substantial worldwide challenge with profound social and economic implications. As the prevalence of AD continues to rise and the population ages, there is an imperative demand for innovative imaging techniques to help improve our understanding of these complex conditions. Photoacoustic (PA) imaging forms a hybrid imaging modality by integrating the high-contrast of optical imaging and deep-penetration of ultrasound imaging. PA imaging enables the visualization and characterization of tissue structures and multifunctional information at high resolution and, has demonstrated promising preliminary results in the study and diagnosis of AD. This review endeavors to offer a thorough overview of the current applications and potential of PA imaging on AD diagnosis and treatment. Firstly, the structural, functional, molecular parameter changes associated with AD-related brain imaging captured by PA imaging will be summarized, shaping the diagnostic standpoint of this review. Then, the therapeutic methods aimed at AD is discussed further. Lastly, the potential solutions and clinical applications to expand the extent of PA imaging into deeper AD scenarios is proposed. While certain aspects might not be fully covered, this mini-review provides valuable insights into AD diagnosis and treatment through the utilization of innovative tissue photothermal effects. We hope that it will spark further exploration in this field, fostering improved and earlier theranostics for AD.
Uncinate fasciculus microstructural organisation and emotion recognition in schizophrenia: controlling for hit rate bias
Authors: Stevens Matthew , Ní Mhurchú Síle , Corley Emma , Egan Ciara , Hallahan Brian , McDonald Colm , Donohoe Gary , Burke Tom
Published: March 2024

Introduction

Schizophrenia (SCZ) is a complex neurodevelopmental disorder characterised by functional and structural brain dysconnectivity and disturbances in perception, cognition, emotion, and social functioning. In the present study, we investigated whether the microstructural organisation of the uncinate fasciculus (UF) was associated with emotion recognition (ER) performance. Additionally, we investigated the usefulness of an unbiased hit rate (UHR) score to control for response biases (i.e., participant guessing) during an emotion recognition task (ERT).

Methods

Fifty-eight individuals diagnosed with SCZ were included. The CANTAB ERT was used to measure social cognition. Specific ROI manual tract segmentation was completed using ExploreDTI and followed the protocol previously outlined by Coad et al. (2020).

Results

We found that the microstructural organisation of the UF was significantly correlated with physical neglect and ER outcomes. Furthermore, we found that the UHR score was more sensitive to ERT subscale emotion items than the standard HR score. Finally, given the association between childhood trauma (in particular childhood neglect) and social cognition in SCZ, a mediation analysis found evidence that microstructural alterations of the UF mediated an association between childhood trauma and social cognitive performance.

Discussion

The mediating role of microstructural alterations in the UF on the association between childhood trauma and social cognitive performance suggests that early life adversity impacts both brain development and social cognitive outcomes for people with SCZ. Limitations of the present study include the restricted ability of the tensor model to correctly assess multi-directionality at regions where fibre populations intersect.
Screening effects of HCN channel blockers on sleep/wake behavior in zebrafish
Authors: Doldur-Balli Fusun , Smieszek Sandra P. , Keenan Brendan T. , Zimmerman Amber J. , Veatch Olivia J. , Polymeropoulos Christos M. , Birznieks Gunther , Polymeropoulos Mihael H.
Published: March 2024

Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels generate electrical rhythmicity in various tissues although primarily heart, retina and brain. The HCN channel blocker compound, Ivabradine (Corlanor), is approved by the US Food and Drug Administration (FDA) as a medication to lower heart rate by blocking hyperpolarization activated inward current in the sinoatrial node. In addition, a growing body of evidence suggests a role for HCN channels in regulation of sleep/wake behavior. Zebrafish larvae are ideal model organisms for high throughput drug screening, drug repurposing and behavioral phenotyping studies. We leveraged this model system to investigate effects of three HCN channel blockers (Ivabradine, Zatebradine Hydrochloride and ZD7288) at multiple doses on sleep/wake behavior in wild type zebrafish. Results of interest included shorter latency to daytime sleep at 0.1 μM dose of Ivabradine (ANOVA, p: 0.02), moderate reduction in average activity at 30 μM dose of Zatebradine Hydrochloride (ANOVA, p: 0.024) in daytime, and increased nighttime sleep at 4.5 μM dose of ZD7288 (ANOVA, p: 0.036). Taken together, shorter latency to daytime sleep, decrease in daytime activity and increased nighttime sleep indicate that different HCN channel antagonists affected different parameters of sleep and activity.
Identification of TBK1 inhibitors against breast cancer using a computational approach supported by machine learning
Authors: Siddiqui Arif Jamal , Jamal Arshad , Zafar Mubashir , Jahan Sadaf
Published: March 2024

Introduction: The cytosolic Ser/Thr kinase TBK1 is of utmost importance in facilitating signals that facilitate tumor migration and growth. TBK1-related signaling plays important role in tumor progression, and there is need to work on new methods and workflows to identify new molecules for potential treatments for TBK1-affecting oncologies such as breast cancer.

Methods: Here, we propose the machine learning assisted computational drug discovery approach to identify TBK1 inhibitors. Through our computational ML-integrated approach, we identified four novel inhibitors that could be used as new hit molecules for TBK1 inhibition.

Results and Discussion: All these four molecules displayed solvent based free energy values of −48.78, −47.56, −46.78 and −45.47 Kcal/mol and glide docking score of −10.4, −9.84, −10.03, −10.06 Kcal/mol respectively. The molecules displayed highly stable RMSD plots, hydrogen bond patterns and MMPBSA score close to or higher than BX795 molecule. In future, all these compounds can be further refined or validated by in vitro as well as in vivo activity. Also, we have found two novel groups that have the potential to be utilized in a fragment-based design strategy for the discovery and development of novel inhibitors targeting TBK1. Our method for identifying small molecule inhibitors can be used to make fundamental advances in drug design methods for the TBK1 protein which will further help to reduce breast cancer incidence.
Unraveling DDIT4 in the VDR-mTOR pathway: a novel target for drug discovery in diabetic kidney disease
Authors: Lu Hai-tao , Jiao Yuan-yuan , Yu Tian-yu , Shi Jing-xuan , Tian Jing-wei , Zou Gu-ming , Liu Lin , Zhuo Li
Published: March 2024

Introduction:

Diabetic kidney disease (DKD) necessitates innovative therapeutic strategies. This study delves into the role of DNA damage-inducing transcription factor 4 (DDIT4) within the VDR-mTOR pathway, aiming to identify a novel target for DKD drug discovery.

Methods:

Transcriptome data from the Gene Expression Omnibus Database were analyzed to assess the expression of mTOR and VDR expression in human renal tissues. Clinical samples from DKD patients and minimal change disease (MCD) controls were examined, and a DKD animal model using 20-week-old db/db mice was established. DDIT4 plasmid transfection was employed to modulate the VDR-mTOR pathway, with its components evaluated using immunohistochemistry, real-time quantitative PCR (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA).

Results:

Changes in the expression of the VDR-mTOR pathway were observed in both DKD patients and the animal model. Overexpression of DDIT4 increased VDR expression and decreased levels of mTOR, p70s6k, and 4E-BP1. Furthermore, DDIT4 treatment regulated autophagy by upregulating LC3I expression and downregulating LC3II expression. Notably, DDIT4 alleviated oxidative stress by reducing the levels of lipid peroxidation product MDA, while simultaneously increasing the levels of superoxide dismutase (SOD) and glutathione (GSH), underscoring the role of DDIT4 in the pathological process of DKD and its potential as a therapeutic target.

Conclusion:

Unraveling DDIT4’s involvement in the VDR-mTOR pathway provides insights for innovative DKD drug discovery, emphasizing its potential as a therapeutic target for future interventions.
Warming affects leaf light use efficiency and functional traits in alpine plants: evidence from a 4-year in-situ field experiment
Authors: Zhou Zijuan , Su Peixi , Yang Jianping , Shi Rui , Ding Xinjing
Published: March 2024

Introduction

Light use efficiency (LUE) is a crucial determinant of plant productivity, while leaf functional traits directly affect ecosystem functions. However, it remains unclear how climate warming affects LUE and leaf functional traits of dominant species in alpine meadows.

Methods

We conducted a 4-year in-situ field warming experiment to investigate the eco-physiological characteristics for a dominant species (Elymus nutans) and a common species (Potentilla anserina) on the Tibetan Plateau. The leaf traits, photosynthesis and fluorescence characteristics were measured, along with the soil physical-chemical properties associated with the two species.

Results and discussions

Experimental warming increased the leaf LUE, maximum photochemical efficiency, non-photochemical quenching, relative water content and specific leaf area for both species. However, there was a decrease in leaf and soil element content. Different species exhibit varying adaptability to warming. Increasing temperature significantly increased the photosynthetic rate, stomatal conductance, transpiration rate, total water content, and specific leaf volume of E. nutans; however, all these traits exhibited an opposite trend in P. anserina. Warming has a direct negative impact on leaf LUE and an indirectly enhances LUE through its effects on leaf traits. The impact of warming on plant photosynthetic capacity is primarily mediated by soil nutrients and leaf traits. These results indicate that the two different species employ distinct adaptive strategies in response to climate change, which are related to their species-specific variations. Such changes can confer an adaptive advantage for plant to cope with environmental change and potentially lead to alterations to ecosystem structure and functioning.
Carboxylic acid accumulation and secretion contribute to the alkali-stress tolerance of halophyte Leymus chinensis
Authors: Wang Huan , Zhao Shuting , Sun Bo , Osman Feisal Mohamed , Qi Zexin , Ding Dan , Liu Xin , Ding Jiale , Zhang Zhian
Published: March 2024

Leymus chinensis is a dominant halophytic grass in alkalized grasslands of Northeast China. To explore the alkali-tolerance mechanism of L. chinensis, we applied a widely targeted metabolomic approach to analyze metabolic responses of its root exudates, root tissues and leaves under alkali-stress conditions. L. chinensis extensively secreted organic acids, phenolic acids, free fatty acids and other substances having -COOH or phosphate groups when grown under alkali-stress conditions. The buffering capacity of these secreted substances promoted pH regulation in the rhizosphere during responses to alkali stress. L. chinensis leaves exhibited enhanced accumulations of free fatty acids, lipids, amino acids, organic acids, phenolic acids and alkaloids, which play important roles in maintaining cell membrane stability, regulating osmotic pressure and providing substrates for the alkali-stress responses of roots. The accumulations of numerous flavonoids, saccharides and alcohols were extensively enhanced in the roots of L. chinensis, but rarely enhanced in the leaves, under alkali-stress conditions. Enhanced accumulations of flavonoids, saccharides and alcohols increased the removal of reactive oxygen species and alleviated oxygen damage caused by alkali stress. In this study, we revealed the metabolic response mechanisms of L. chinensis under alkali-stress conditions, emphasizing important roles for the accumulation and secretion of organic acids, amino acids, fatty acids and other substances in alkali tolerance.
Effects of grazing exclusion on soil microbial diversity and its functionality in grasslands: a meta-analysis
Authors: Shu Xiangyang , Ye Qinxin , Huang Han , Xia Longlong , Tang Hao , Liu Xingyi , Wu Jianwei , Li Yiding , Zhang Yanyan , Deng Liangji , Liu Weijia
Published: March 2024

Grazing exclusion (GE) is considered an effective strategy for restoring the degradation of overgrazed grasslands on the global scale. Soil microbial diversity plays a crucial role in supporting multiple ecosystem functions (multifunctionality) in grassland ecosystems. However, the impact of grazing exclusion on soil microbial diversity remains uncertain. Here, we conducted a meta-analysis using a dataset comprising 246 paired observations from 46 peer-reviewed papers to estimate how GE affects microbial diversity and how these effects vary with climatic regions, grassland types, and GE duration ranging from 1 to 64 years. Meanwhile, we explored the relationship between microbial diversity and its functionality under grazing exclusion. Overall, grazing exclusion significantly increased microbial Shannon (1.9%) and microbial richness (4.9%) compared to grazing group. For microbial groups, GE significantly increased fungal richness (8.6%) and bacterial richness (5.3%), but decreased specific microbial richness (-11.9%). The responses of microbial Shannon to GE varied among climatic regions, grassland types, and GE duration. Specifically, GE increased microbial diversity in in arid, semi-arid, and dry sub-humid regions, but decreased it in humid regions. Moreover, GE significantly increased microbial Shannon in semidesert grasslands (5.9%) and alpine grasslands (3.0%), but not in temperate grasslands. Long-term (>20 year) GE had greater effects on microbial diversity (8.0% for Shannon and 6.7% for richness) compared to short-term (<10 year) GE (-0.8% and 2.4%). Furthermore, grazing exclusion significantly increased multifunctionality, and both microbial and plant Shannon positively correlated with multifunctionality. Overall, our findings emphasize the importance of considering climate, GE duration, and grassland type for biodiversity conservation and sustainable grassland ecosystem functions.
Intercultural communication competence and job burnout in MNC employees: the mediation role of job stress
Authors: Xie Xiaoxia , Tu Yulu , Huang Chienchung
Published: March 2024

This study examined the relationship between intercultural communication competence (ICC) and job burnout, as well as the mediating effects of job stress, using data collected from employees (n = 1,064) from a Chinese multinational corporation in Brunei. Through regression analysis and mediation effect tests, we found that ICC was negatively associated with job burnout (β = −0.19, p < 0.001) and job stress (β = −0.08, p < 0.001). Job stress was positively associated with job burnout (β = 0.65, p < 0.001). Job stress played a partial mediating role between ICC and job burnout. The total effect of ICC on job burnout was −0.19, the direct effect was −0.14, and the indirect effect of ICC via job stress was −0.05. The findings call for ICC training for employees in multinational corporations.
Long-term effects of combined mindfulness intervention and app intervention compared to single interventions during the COVID-19 pandemic: a randomized controlled trial
Authors: Karing Constance
Published: March 2024

Objectives

The study examines the short-, middle-, and long-term effects of a combined intervention (face-to-face mindfulness intervention plus the mindfulness app 7Mind), compared to single interventions (face-to-face mindfulness intervention alone and an intervention via app 7Mind alone). The subgroups were compared with an active control group on mindfulness, mindful characteristics, mental health, emotion regulation, and attentional abilities during the COVID-19 pandemic. Additionally, the study explores whether students’ engagement with the app and their formal mindfulness practice at home improves intervention outcomes.

Methods

The study employs a randomized controlled trial approach involving three intervention groups and an active control group, with two follow-ups conducted over 12 months. The study included 177 university students who were randomly assigned to a mindfulness group (n = 42), a mindfulness app group (7Mind app, n = 44), a mindfulness + app group (n = 45), and an active control group (n = 46). The duration of the interventions was 4 weeks. The outcome variables were assessed at pre- and post-intervention, at 4 and 12 months post-intervention.

Results

At post-intervention and during both follow-ups, students in the combined mindfulness intervention did not demonstrate better outcomes compared to students in the single interventions or the active control group across all measures. Additionally, no statistically significant difference was observed between all interventions and the active control groups on any of the measures. However, it is noteworthy that all intervention groups and the active control group exhibited improvement in mindfulness, body awareness, emotion regulation, stress, and attentional abilities over the short, medium, and long term. Moreover, higher app usage in the app groups was significantly associated with increased body awareness. However, greater app use was also correlated with higher stress.

Conclusion

The results suggest that the mindfulness intervention and the mindfulness app were similar to the active control condition (communication training) on the investigated variables in the short, medium, and long term. Furthermore, an increased use of a mindfulness app can negatively affect stress.