bluuebunny/crossref_metadata_2025 huggingface dataset:
Cultural Synergy in Islamic Educational Leadership: Developing an Inclusive Model for Enhancing Management Effectiveness and Educational Quality in Culturally Diverse Institutions
Authors: Walid Ahmad , Hidayati Suci , Ramli Nurleli
Published: August 2024

This research aims to develop an ideal leadership model for Islamic educational institutions based on cultural diversity. The focus of this research is to understand how the interaction between leadership and cultural diversity affects management effectiveness and the quality of education in these institutions. This study uses a qualitative approach with a case study design, where data is collected through in-depth interviews, participatory observations, and documentation analysis in several Islamic educational institutions in Indonesia that have a high level of cultural diversity. The results show that the success of leadership in this context is highly dependent on the ability of leaders to adapt to local cultural values, integrate those cultures into management practices, and create an inclusive and participatory environment. The proposed leadership model emphasizes the importance of flexibility, inclusivity, and respect for cultural diversity. The implications of this study show that a leadership approach that is responsive to cultural diversity can improve the effectiveness of management and the quality of education in Islamic educational institutions. The study also recommends the development of leadership training programs that focus on cultural diversity to strengthen leaders' ability to face complex challenges.
PERUBAHAN BUDAYA KERJA PEGAWAI NEGERI SIPIL SETELAH ADANYA PANDEMI COVID 19 PADA DINAS PENANAMAN MODAL DAN PELAYANAN TERPADU SATU PINTU KOTA TARAKAN PROVINSI KALIMANTAN UTARA
Authors: Zulaika Siti , Ravi Abdul
Published: August 2024

Pandemi COVID-19 membuat manusia terlalu nyaman dengan bekerja dari rumah (WFH), mengakibatkan pekerja melupakan tugas dan kedisiplinan saat pandemi mereda. Kembali bekerja di kantor (WFO) tidak disukai banyak pekerja, terutama generasi muda yang enggan meninggalkan kenyamanan tiga tahun bekerja di rumah. Penelitian ini menganalisis perubahan budaya kerja Pegawai Negeri Sipil di Dinas Penanaman Modal dan Pelayanan Terpadu Satu Pintu Kota Tarakan, Kalimantan Utara, setelah pandemi COVID-19. Metode kualitatif eksploratif dengan pendekatan induktif digunakan dengan pengumpulan data melalui wawancara, observasi, dan dokumentasi. Hasil analisis menunjukkan dua tema utama perubahan budaya kerja: perubahan lingkungan kerja (teknologi, fasilitas, motto organisasi, gaya kepemimpinan, dan sistem penghargaan) dan perubahan perilaku individu (ketidakpatuhan terhadap waktu dan berpakaian). Kesimpulannya, Penelitian ini mengidentifikasi 25 label dari 7 kategori terkait perubahan budaya kerja Pegawai Negeri Sipil pasca pandemi COVID-19.Kata Kunci: Perubahan Budaya Kerja, Pegawai Negeri Sipil, Pandemi Covid 19
Logoterapi Yönelimli Sağaltım Programının Bireylerin Ruh Sağlığı, Hayatın Anlam ve Amacı Düzeylerine Etkisi
Authors: Okcu Cüneyt , Demir Volkan
Published: August 2024

Bu çalışmanın amacı varoluşçu felsefeden temellendirilmiş Logoterapi Yönelimli Grup Çalışmasının bireylerin ruh sağlığı, hayatın anlam ve amacı düzeylerine etkililiğini incelemektir. Çalışma, öntest-sontest modelli yarı deneysel bir araştırmadır. Çalışmanın bağımsız değişkeni; öntest ve sontest arasında araştırma grubuna uygulanan Logoterapi Yönelimli Grup Çalışmasıdır. Araştırmanın bağımlı değişkeni ise çalışma grubunda yer alan bireylerin ruh sağlığı, hayatın anlam ve amacı düzeyleridir. Araştırma grubunu katılım kriterlerini sağlayan 25 ila 40 yaşlarında 5’i kadın 6’sı erkek 11 birey oluşturmaktadır. Çalışmada katılımcılara çalışma başlamadan önce ve on haftanın sonunda Ruh Sağlığı Sürekliliği Kısa Formu, Hayatın Amacı ve Anlamı Ölçeği uygulanmıştır. Çalışma grubuna on oturumluk Logoterapi Yönelimli Grup Çalışması uygulanmıştır. Çalışmada elde edilen veriler Wilcoxon İşaretli Sıra Testi kullanılarak analiz edilmiştir. Yapılan istatiksel değerlendirmeler sonucunda katılımcıların Hayatın Amacı ve Anlamı ölçek puanları ile Ruh Sağlığı Sürekliliği alt boyutlarından Duygusal, Psikolojik ve Sosyal İyi Olma Hali puanlarında anlamlı düzeyde farklılık tespit edilmiştir. Araştırmanın sonuçları, sınırlılıkları ve güçlü yanları alanyazın ışığında tartışılmıştır.
STEM in Croatia: Americanization of Education in Decline
Authors: Palijaš Alen
Published: August 2024

This paper critically examines the adaptation of American STEM educational practices within the Croatian education system, assessing their suitability and effectiveness given the significant socio-economic and demographic differences between the two countries. Through comparative analysis, the study juxtaposes the STEM education frameworks of the USA and Croatia, utilizing data from educational policy documents, student performance records, and demographic statistics to explore the transposition of educational models. The findings indicate that the direct transplantation of American STEM educational strategies into the Croatian context has not been entirely successful, due to Croatia's unique industrial landscape and ongoing population decline. The study highlights significant disparities in the effectiveness of STEM education, which are exacerbated by these national differences. The implications of this research are twofold. First, it suggests that countries need to consider their specific industrial and demographic contexts when adopting foreign educational models. Second, the study raises concerns about the sustainability of the Croatian education system's approach to preparing students for future STEM careers. The results call for a reevaluation of policy strategies, suggesting that more localized adaptations of STEM education may be necessary to address the unique challenges faced by countries like Croatia.
STEM Education and Labor Needs: Engineering Graduates in Ethiopia
Authors: Teshome Asmera , Oumer Jeilu
Published: August 2024

This study examined the alignment between the supply of STEM skills by higher education institutions and the demand for these skills in the labor market in Ethiopia, employing a mixed-methods approach. Quantitative data from 275 respondents were analyzed using mean, standard deviation, and paired sample t-tests, while thematic analysis was applied to qualitative data. The results revealed significant mismatches between the skills provided by educational institutions and those required by the labor market, with the greatest disparities found in generic skills, followed by technical and interpersonal skills, and the least in discipline-specific skills. The study highlights the urgent need for higher education institutions to enhance their collaboration with industry stakeholders to develop curricula that effectively address these gaps. Recommendations include conducting regular market needs assessments, integrating external expert lectures, and applying project-based learning to foster critical and innovative thinking skills among students, preparing them more effectively for employment.
Analisis Kinerja Pengelolaan Sampah di Kabupaten Pangandaran
Authors: Ratna Suminar Desi
Published: August 2024

Pelayanan pengelolaan sampah sangat penting untuk menjaga kualitas lingkungan terutama di daerah kota wisata seperti Kabupaten Pangandaran. Terjadinya penumpukan sampah di lokasi wisata menyebabkan ketidaknyamanan terhadap pengunjung wisata. Berbagai upaya telah dilakukan oleh Pemerintah Kabupaten Pangandaran untuk meningkatkan pelayanan pengelolaan sampah, tetapi penumpukan sampah kerap terjadi di daerah pantai, baik itu sampah dari pengunjung atau pun sampah kiriman dari sungai. Oleh sebab itu, diperlukan  Indeks Kinerja Pengelolaan Sampah (IKPS) sebagai alat ukur untuk mengetahui seberapa besar kinerja pengelolaan sampah yang dilakukan oleh Pemerintah Kabupaten Pangandaran. Penelitian ini bertujuan untuk menghitung dan menginterprestasikan Nilai IKPS. Metode yang digunakan adalah menggunakan perhitungan nilai Indeks Kinerja Pengelolaan Sampah. Hasil dari perhitungan nilai IKPS, Kabupaten Pangandaran memiliki nilai IKPS sebesar 43,18 dengan kategori Sangat Kurang, artinya kinerja pengelolaan sampah di Kabupaten Pangandaran belum maksimal dan masih perlu ditingkatkan.
The sperm-specific K+ channel Slo3 is inhibited by albumin and steroids contained in reproductive fluids
Authors: Lorenz Johannes , Eisenhardt Clara , Mittermair Teresa , Kulle Alexandra E. , Holterhus Paul Martin , Fobker Manfred , Boenigk Wolfgang , Nordhoff Verena , Behre Hermann M. , Strünker Timo , Brenker Christoph
Published: August 2024

To locate and fertilize the egg, sperm probe the varying microenvironment prevailing at different stages during their journey across the female genital tract. To this end, they are equipped with a unique repertoire of mostly sperm-specific proteins. In particular, the flagellar Ca2+ channel CatSper has come into focus as a polymodal sensor used by human sperm to register ligands released into the female genital tract. Here, we provide the first comprehensive study on the pharmacology of the sperm-specific human Slo3 channel, shedding light on its modulation by reproductive fluids and their constituents. We show that seminal fluid and contained prostaglandins and Zn2+ do not affect the channel, whereas human Slo3 is inhibited in a non-genomic fashion by diverse steroids as well as by albumin, which are released into the oviduct along with the egg. This indicates that not only CatSper but also Slo3 harbours promiscuous ligand-binding sites that can accommodate structurally diverse molecules, suggesting that Slo3 is involved in chemosensory signalling in human sperm.
Health journalism: a bibliometric analysis of research themes and future directions
Authors: Feng Shi
Published: August 2024

The body of health journalism research literature remains scattered across various disciplines and requires comprehensive understanding. This study aims to enhance researchers’ comprehension of the field, by presenting a systematic review of SSCI-indexed articles. Findings reveal two peaks in health journalism research from 1994 to 2023: during the 2009 H1N1 influenza and the COVID-19 outbreak. Using bibliographic coupling analysis, it was possible to define 10 major research themes from the review. They were: How health stories are framed in the news; How audiences engage with health information online; How constructive journalism can improve the news reporting of public health crisis; How fact-checking can improve the news reporting of public health crisis; How health stories are framed from science journalism perspective; Why citizen journalism is significant in health news reporting; How health journalists perceive their journalistic role; Who serves as the news source for health news reporting; How health professionals impact health news reporting; and How peace journalism can be used for health news reporting on vulnerable populations. This research provides insights into the current state of health journalism research and outlines potential areas for further exploration in health journalism, spanning topics such as women and other marginalized communities in health reporting.
In vitro and ex vivo comparison of reactive oxygen-releasing granules for internal tooth bleaching
Authors: Mayer Romy M. , Gubler Andrea , Attin Thomas , Zehnder Matthias
Published: August 2024

Introduction

Traditionally, internal tooth bleaching was performed using sodium perborate slurries. These are banned in some areas for potential carcinogenic effects. More recently, highly concentrated hydrogen peroxide gels have been used, which may cause dentin degradation. Consequently, the search for ideal internal tooth bleaching agents is still on. This study compared pure ROS-releasing granules regarding their liberation of oxidizing species, pH induction, bleaching of blood-stained dentin, and effects on mechanical dentin properties.

Materials and methods

The ROS-releasing granules under investigation were sodium perborate, carbamide peroxide, and sodium percarbonate in aqueous suspension (4:3, wt/wt). The bleaching efficacy of these suspensions was compared in blood-stained human dentin (n = 6) ex vivo. In addition, effects on mechanical dentin integrity were tested using bovine dentin beams (n = 9) exposed to a 3-point bending test (ISO 4049) after immersion in test suspensions or control solutions (35% H2O2 and physiological saline) for 1 week.

Results

Granules release between 21.5% and 35.2% (wt/wt) of H2O2 equivalent. The sodium-containing granules (perborate and percarbonate) caused an alkaline pH of 10.3 and 10.6, respectively. The carbamide peroxide suspension was acidic (pH 3.9), as was the 35% H2O2 solution used as a control (pH 2.2). All the suspensions bleached the blood-stained dentin, albeit with a lesser overall effect by sodium percarbonate (one-way ANOVA and Tukey's HSD, p < 0.05). The acidic preparations caused a severe (over 50%) reduction in flexural strength of the dentin (p < 0.05 compared to physiological saline solution), while the alkaline counterparts did not.

Conclusions

Sodium perborate granules in aqueous suspension combined good de-staining properties with limited untoward effects on dentin integrity. Further studies are required to identify alternative compounds with a lesser general health concern.
Exploring Bayesian network model with noise filtering for rainfall-induced landslide susceptibility assessment in Fujian, China
Authors: Zhou Suhua , Li Jinfeng , Zhang Jiuchang , Xu Zhiwen , Lu Xianzhui
Published: August 2024

Machine learning models have been increasingly popular in landslide susceptibility mapping based on the correlations among landslides and their inducing factors. However, mislabeled data in model training sets would deteriorate model accuracy. This study employed a Bayesian network to analyze influencing factors on landslides in Fujian Province, China, prone to typhoons and landslides. An inventory of 5,992 historical landslides informs Bayesian network modeling, with ten geoenvironmental factors as predictors. We introduced a progressive noise filtering method to mitigate the mislabeling effects of non-landslide points. The results show that altitude, wind speed, and lithology are the most important factors of landslides in the study area. The accuracy of the resultant landslide susceptibility map was verified using the area under the receiver operating characteristic curve (AUC) and Moran’s I index. The AUC value was improved from 0.838 to 0.931 during the progressive noise filtering. The correlation between historical landslide number density (LND) and resultant landslide susceptibility index (LSI) was evaluated. The Local Indicators of Spatial Association based on Moran’s I index shows consistent distribution patterns for high LND and high LSI regions. This study provides a useful reference for reliable landslide susceptibility mapping in the study area and similar areas.
Acute effects of exercise on macro- and microvasculature in individuals with type 1 diabetes – a secondary outcome analysis
Authors: Saloň Adam , Schmid-Zalaudek Karin , Steuber Bianca , Müller Alexander , Moser Othmar , Alnuaimi Suhaila , Fredriksen Per Morten , Ngwenchi Nkeh-Chungag Benedicta , Goswami Nandu
Published: August 2024

Background

Type 1 diabetes is a chronic autoimmune disease associated with insulin-producing beta cell destruction, declining insulin secretion, and elevated blood glucose. Physical activity improves glycaemic control and cardiovascular health. This study explores acute effects of maximal exhaustion induced by a cardiopulmonary exercise on macro- and microvascular parameters in type 1 diabetes.

Methodology

Twenty-five participants with type 1 diabetes (14 males, 11 females), aged 41.4 ± 11.87 years, BMI 23.7 ± 3.08, completed a repeated-measure study. Measurements pre-, post-, 30- and 60-minutes post-exhaustion involved a maximal incremental cardio-pulmonary exercise test. Macro- and microvascular parameters were assessed using VICORDER® and retinal blood vessel image analysis. Repeated measures ANOVA in SPSS (Version 27.0) analysed data.

Results

Post-exercise, heart rate increased (p<.001), and diastolic blood pressure decreased (p=.023). Diabetes duration correlated with pulse wave velocity (r=0.418, p=.047), diastolic blood pressure (r=0.470, p=.023), and central retinal arteriolar equivalent (r=0.492, p=.023).

Conclusion

In type 1 diabetes, cardiopulmonary exercise-induced exhaustion elevates heart rate and reduces diastolic blood pressure. Future research should explore extended, rigorous physical activity protocols for greater cardiovascular risk reduction.
Gene-environment interaction in functional hypothalamic amenorrhea
Authors: Barbagallo Federica , Bosoni David , Perone Valeria , Cucinella Laura , Dealberti Davide , Cannarella Rossella , Calogero Aldo E. , Nappi Rossella E.
Published: August 2024

Functional hypothalamic amenorrhea (FHA) is a common cause of amenorrhea and chronic anovulation in adolescent girls and young women, diagnosed after excluding other organic causes. It is commonly associated with calorie restriction, excessive physical exercise, and psychosocial stress. These stressors alter the pulsatile secretion of gonadotropin-releasing hormone, leading to a chronic condition of hypoestrogenism and significant health consequences. Recent evidence has highlighted a genetic predisposition to FHA that could explain interindividual variability in stress response. Indeed, not all women experience FHA in response to stress. Rare variants in genes associated with idiopathic hypogonadotropic hypogonadism have been identified in women with FHA, suggesting that these mutations may contribute to an increased susceptibility of women to the trigger of stress exposure. FHA appears today as a complex disease resulting from the combination of genetic predisposition, environmental factors, and epigenetic changes. Furthermore, the genetic background of FHA allows for the hypothesis of a male counterpart. Despite the paucity of data, preliminary findings indicate that an equivalent condition of FHA exists in men, warranting further investigation. This narrative review aims to summarize the recent genetic evidence contributing to the pathophysiology of FHA and to raise awareness on a possible male counterpart.
Implementing a sustainable integrated agroforestry system for the cultivation of Ilex paraguariensis
Authors: Comolli Luis R. , Schegg Esteban , Infuleski Cristian , Munareto Nestor , Fassola Hugo , von Wallis Alejandra , Bulfe Nardia M. , González Paola , Barth Sara R. , Gauchat María Elena , Wyss Fabio
Published: August 2024

In this work, we advocate agroforestry as a sustainable agricultural method that leverages biodiversity and ecosystem services, simultaneously tackling the problems of adaptation and mitigation to climate change, and of land restoration for sustainable agriculture across scales. While the rise of industrial agriculture has been instrumental in addressing the food demands of an expanding global population, enhancing food quality, yield, productivity, and efficiency, we must now reckon with the consequences. This advancement, which prioritizes simplification, specialization, and external inputs, has escalated detrimental externalities including deforestation, biodiversity loss, soil degradation, pollution, and an increase in greenhouse gases, contributing significantly to global warming and to exacerbated environmental crises. These demand urgent attention. In response, various agricultural methodologies such as organic, biodynamic, ecological, and biological farming have emerged, attempting to propose alternatives. However, these methods have yet to significantly alter the trajectory of mainstream agriculture. For over two decades, we have devoted our efforts to developing and refining a multispecies integrated agroforestry system for the sustainable cultivation of Ilex paraguariensis, “yerba mate,” in the subtropical north-east of Argentina. With “integrated” we mean that the trees are planted within the I. paraguariensis distribution, not between alleys as in “alley cropping” or “hedgrow intercropping.” The experimental work we present here was designed and implemented to enable data comparisons across consociations of multiple species of trees, at a relevant experimental scale. We achieve soil preservation and restoration, productivity comparable to or exceeding monocultures, and a significant increase in resiliency, particularly evidenced during the extreme climate events of spring and summer 2021 and 2022. These results underscore agroforestry’s potential for climate change mitigation and adaptation.
Enhancement of the stability and cytotoxicity of berberine by liposomal nanocarriers for gastric cancer treatment and its application in gummy candy
Authors: Abolhasanzadeh Narges , Dehghan Gholamreza , Abbaspour-Ravasjani Soheil
Published: August 2024

Introduction

Berberine (BER), an isoquinoline alkaloid derived from the plant Berberis Vulgaris, is traditionally used to treat different types of disorders, such as cancer. However, its therapeutic application is limited due to poor solubility and low bioavailability. So, the main objective of the present work was to synthesize BER-loaded liposomes to enhance the solubility of BER. BER-loaded liposomes were synthesized using the thin-film hydration method.

Methods

The prepared liposomes were characterized for size, surface charge, in vitro release, and cytotoxicity. Then, the synthesized nano-liposomes were used to enrich gummy candies, and physicochemical properties such as water activity (aw), instrumental texture, and sensory perception of the products were tested.

Results and Discussion

The cell viability assay was performed on MKN-45P gastric cancer cell lines, and the results revealed that BER-loaded liposome had better cytotoxicity on MKN-45P cells than free BER. The IC50 values were calculated to be 66.72 µg/mL and 52.58 µg/mL for free BER and BER-loaded liposomes, respectively. Flow cytometric analysis demonstrated a significant anticancer effect of BER-loaded liposomes compared to free BER. These findings indicate that encapsulating BER preserves its antioxidant activity and enhances its bioavailability.
Amnestic syndrome in the course of seronegative limbic encephalitis complicated by drug-resistant epilepsy: a case report
Authors: Łoś Kacper , Kulikowska Joanna , Chorąży Monika , Kułakowska Alina , Waszkiewicz Napoleon , Galińska-Skok Beata
Published: August 2024

We present the case of a 35-year-old female patient admitted to the hospital with symptoms of rapidly increasing disturbances of consciousness and fever for 48 hours. A lumbar puncture, bacteriological and virological examinations, and initial imaging studies did not show abnormalities. Brain magnetic resonance imaging (MRI), repeated several times, showed hyperintense confluent lesions in both temporal lobes and atrophy of both hippocampi. General examination, cerebrospinal fluid culture, the panel of antineuronal antibodies, and tumor markers remained negative on subsequent repeats. Despite several laboratory and imaging studies, the etiology of the disease could not be established, infections were excluded, and no autoantibodies were found. A diagnosis of probable limbic encephalitis, amnestic syndrome resulting from organic brain damage, and drug-resistant epilepsy was made. The patient, with limbic encephalitis complicated by drug-resistant status epilepticus, was treated with cycles of immunoglobulin and subsequent plasmapheresis. She was then transferred to the Department of Psychiatry for diagnosis and treatment of intermittent psychotic disorders. During hospitalization, the patient was observed to have multiple epileptic seizures with temporal and frontal morphology, amnestic syndrome with confabulations, and periodic psychotic disorders with the occurrence of visual hallucinations. Antiepileptic treatment was escalated by including cenobamate in increasing doses. To control the mental disorders, duloxetine, tiapride, and cognitive function exercises were introduced. There was a slight improvement in memory, a cessation of confabulations, and an emergence of the patient’s criticism of the symptoms presented. The psychotic symptoms subsided, and the number of epileptic seizures decreased. The described case portrays a unique co-occurrence of disease symptoms that are difficult to treat. It shows the therapeutic difficulties that can occur in patients with suspected autoimmune encephalitis. Furthermore, it shows the need for multispecialty care of a patient with psychotic symptoms in the course of epilepsy accompanied by amnestic syndrome.
Thymic development of human natural killer T cells: recent advances and implications for immunotherapy
Authors: Pellicci Daniel G. , Tavakolinia Naeimeh , Perriman Louis , Berzins Stuart P. , Menne Christopher
Published: August 2024

Invariant natural killer T (iNKT) cells are a subset of lipid-reactive, unconventional T cells that have anti-tumor properties that make them a promising target for cancer immunotherapy. Recent studies have deciphered the developmental pathway of human MAIT and Vγ9Vδ2 γδ-T cells as well as murine iNKT cells, yet our understanding of human NKT cell development is limited. Here, we provide an update in our understanding of how NKT cells develop in the human body and how knowledge regarding their development could enhance human treatments by targeting these cells.
MiRNA-based therapeutic potential in multiple sclerosis
Authors: Zabalza Ana , Pappolla Agustin , Comabella Manuel , Montalban Xavier , Malhotra Sunny
Published: August 2024

This review will briefly introduce microRNAs (miRNAs) and dissect their contribution to multiple sclerosis (MS) and its clinical outcomes. For this purpose, we provide a concise overview of the present knowledge of MS pathophysiology, biomarkers and treatment options, delving into the role of selectively expressed miRNAs in clinical forms of this disease, as measured in several biofluids such as serum, plasma or cerebrospinal fluid (CSF). Additionally, up-to-date information on current strategies applied to miRNA-based therapeutics will be provided, including miRNA restoration therapy (lentivirus expressing a specific type of miRNA and miRNA mimic) and miRNA inhibition therapy such as antisense oligonucleotides, small molecules inhibitors, locked nucleic acids (LNAs), anti-miRNAs, and antagomirs. Finally, it will highlight future directions and potential limitations associated with their application in MS therapy, emphasizing the need for improved delivery methods and validation of therapeutic efficacy.
Extracellular Vesicles & Co.: scaring immune cells in the TME since ever
Authors: Rodolfo Carlo , Campello Silvia
Published: August 2024

The health tissue surrounding a solid tumor, namely the tumor microenvironment (TME), is an extremely complex universe of cells, extracellular matrix, and signals of various nature, that support and protect the growth of cancer cells. The interactions taking place between cancer cells and the TME are crucial not only for tumor growth, invasion, and metastasis but they also play a key role in modulating immune system responses to cancer, and vice-versa. Indeed, tumor-infiltrating immune cells (e.g., T lymphocytes and natural killers) activity is greatly affected by signals (mostly ligands/receptors and paracrine) they receive in the TME, which frequently generate an immunosuppressive milieu. In the last years, it has become evident that soluble and receptor signaling is not the only way of communication between cells in the TME, with extracellular vesicles, such as exosomes, playing a central role. Among the different new kind of vesicles recently discovered, migrasomes look like to be of extreme interest as they are not only different from the others, but also have been reported as able to deliver a very heterogeneous kind of messages, able to profoundly affect recipient cells’ behavior. Indeed, the role played by the different classes of extracellular vesicles, especially in the TME, relies on their not-directional diffusion from the originating cells, while migrasomes released from migrating cells do have a directional effect. Migrasomes biology and their involvement in cancer progression, dissemination, and resistance to therapy is still a largely obscure field, but with promising development foreseen in the next future.
Inflammatory response and parasite regulation in acute toxoplasmosis: the role of P2X7 receptor in controlling virulent atypical genotype strain of Toxoplasma gondii
Authors: Prado-Rangel Thuany , Moreira-Souza Aline Cristina Abreu , da Silva Sthefani Rodrigues Batista , Barboza-Araujo Thais , Castro-Junior Archimedes Barbosa , Ramos Isalira Peroba Rezende , Takiya Christina Maeda , Vommaro Rossiane Claudia , Coutinho-Silva Robson
Published: August 2024

Toxoplasmosis is a globally significant disease that poses a severe threat to immunocompromised individuals, especially in Brazil, where a high prevalence of virulent and atypical strains of Toxoplasma gondii is observed. In 1998, the EGS strain, exhibiting a unique infection phenotype, was isolated in Brazil, adding to the complexity of strain diversity. The P2X7 receptor is critical in inflammation and controlling intracellular microorganisms such as T. gondii. However, its genetic variability can result in receptor dysfunction, potentially worsening susceptibility. This study investigates the role of the P2X7 receptor during acute infection induced by the EGS atypical strain, offering insight into the mechanisms of T. gondii infection in this context. We infected the female C57BL/6 (WT) or P2X7 knockout (P2X7−/−) by gavage. The EGS infection causes intestinal inflammation. The P2X7−/− mice presented higher parasite load in the intestine, spleen, and liver. The absence of the P2X7 receptor disrupts inflammatory cell balance by reducing NLRP3, IL-1β, and Foxp3 expression while increasing IFN-γ expression and production in the intestine. In the liver, P2X7-/- animals demonstrate diminished inflammatory infiltrate within the portal and lobular regions concurrent with an enlargement of the spleen. In conclusion, the infection of mice with the EGS strain elicited immune alterations, leading to acute inflammation and cytokine dysregulation, while the P2X7 receptor conferred protection against parasitic proliferation across multiple organs.
Imidazole propionate in type 2 diabetes mellitus and cardiovascular diseases: a mini review
Authors: Xu Qian , Wang Wenting , Li Yiwen , Liu Yanfei , Liu Yue
Published: August 2024

Oral and gut microbiota can interact with the host by producing a diverse range of bioactive metabolites, thereby influencing overall host health. Imidazole propionate (ImP), a histidine-derived metabolite produced by microbes associated with diabetes mellitus, has attracted considerable attention on account of its roles in metabolic and cardiovascular diseases. In this article, we review the metabolic pathways of ImP, as well as its roles and therapeutic potential in type 2 diabetes mellitus and cardiovascular diseases. Future research should focus on key enzymes and regulatory factors in the ImP metabolic pathway, interactions with other metabolites, and conduct large-scale clinical studies to gain a more comprehensive understanding of the role of ImP in diverse populations and disease contexts. Moreover, targeted interventions against ImP could provide novel strategies for preventing and treating metabolic and cardiovascular diseases.
Exploring the gut microbiome and immunological landscape in kidney cancer: a Mendelian randomization analysis
Authors: Lv Shihui , Guo Qian , He Yuhan , Yu Zhixian , Zhan Xianjing , Li Hang , Pan Yue
Published: August 2024

Introduction

Kidney cancer (KC) is a significant health burden globally, with over 400,000 new cases estimated in 2020. The prognosis of KC is influenced by various factors, including tumor spread, pathological characteristics, and molecular genetic changes. Recent studies have emphasized the involvement of gut microbiota and the immune system’s contribution in the onset of KC. This extensive research endeavor sought to investigate the potential associations between diverse immune cell phenotypes, specific gut microbiota species, and their impact on the risk of developing KC, alongside the examination of circulating inflammatory proteins.

Methods

Adhering to the STROBE-MR guidelines, our investigation involved a two-stage Mendelian randomization (2SMR) analysis grounded on three fundamental assumptions: relevance, independence, and exclusion restriction. The exposure data utilized in this study originated from genome-wide association studies (GWAS) specifically designed to explore immune traits, inflammatory proteins, and gut microbiota compositions.

Results

Our analysis identified 25 immune phenotypes, 4 circulating inflammatory proteins, and 12 gut microbiota features that exhibited significant causal associations with KC (P < 0.05). 10 immune phenotypes were protective against KC, while 15 were risk factors. Among the inflammatory proteins, CCL28 and IL-2 were protective, whereas FGF-23 and β-NGF were risk factors. Gut microbiota features associated with reduced KC risk included biosynthetic pathways involving amino acids and specific bacterial genera, whereas others, like Butyrivibrio crossotus and Odoribacter splanchnicus, were risk factors.

Conclusion

Immune, inflammatory, and gut microbiota factors impact KC development. Identified factors hint at biomarkers and therapeutic targets. It is very important to understand the relationship between these factors and KC.
Neuroendocrine neoplasms of the thymus
Authors: Barone Paul D. , Zhang Chen
Published: August 2024

Neuroendocrine neoplasms of the thymus (tNENs), including typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma, are rare tumors with scarce clinical and pathological data available in the literature. They share many common features with neuroendocrine neoplasms in other organs, such as those in the lungs, while demonstrating some distinct clinical and pathological features. This review aims to give an updated overview of each category of tNENs, focusing primarily on the pathologic diagnosis and differential diagnosis of these tumors.
Evaluation of good review practices in member authorities of the East African Medicines Regulatory Harmonisation initiative: strategies for alignment with African medicines agency
Authors: Ngum Nancy , Ndomondo-Sigonda Margareth , Habonimana Rémy , Siyoi Fred , Irasabwa Clarisse , Ojukwu Julia , Apolinary Felchism , Okello Andrew , Ahmada Sabrina , Walker Stuart , Salek Sam
Published: August 2024

Introduction

The East African Community Medicines Regulatory Harmonisation (EAC-MRH) programme was established to address challenges faced by national regulatory authorities (NRAs) of the region. Work sharing through joint assessments and inspections was adopted to manage limited resources and capacity; however, NRA good review practices (GrevP) are also a key determinant to success. This study evaluated GReVP among the EAC-MRH NRAs and mapped required strategies for countries to align themselves with the African Medicines Agency (AMA).

Methods

A validated questionnaire (Optimising Efficiency in Regulatory Agency—OpERA) that standardises and captures review processes was completed by the head of the medicines registration division in each NRA. A country report based on the completed questionnaire was developed for each NRA and validated by the heads of the respective authorities.

Results

The population and size of the NRAs vary and four of the countries have semi-autonomous authorities and three NRAs are autonomous. The Burundi and South Sudan authorities were fully government funded, Kenya and Uganda entirely from fees, while Rwanda, Tanzania and Zanzibar were partially funded from different sources. All authorities except South Sudan, which does not receive or review applications had backlogs. Authority fees varied based on the different application categories. Key milestones for standardised regulatory processes are implemented in all authorities. Queue times range from a few weeks to about one year. Three NRAs use internal technical agency staff for scientific assessments and three use both internal and external experts. Clock stop time varies and target timelines for review committee range from one day to three months. All the NRAs implement some best practices on quality measures, transparency and communication. Some have activities for transparency improvement but with minimal attention to training and education. Most employ some quality decision-making practices.

Discussion

GrevP in EAC-MRH NRAs still needs to be improved and it is imperative that these authorities streamline and harmonise their practices. Increasing human resources and an investment in training and education of staff will enable the implementation of all measures for GRevP. This is vital, as the effectiveness and efficiency of the AMA will depend on the strength of these NRAs.
The current application of 3D printing simulator in surgical training
Authors: Jiang Yang , Jiang Hanyu , Yang Zhikun , Li Ying
Published: August 2024

In the rapidly evolving field of medical education, the integration of innovative technologies has become paramount to enhance the training and proficiency of future surgeons. Among these advancements, the application of 3D printing technology stands out as a useful tool in surgical training. The advantages of the 3D printing model include customization, re-usability and low-cost. The average cost of the 3D printing simulators was between $100–1000. However, there were extremely high potential labor cost during the 3D printing that hadn’t been calculated into. Additionally, in the current stage, the 3D printing simulator still have specific limitations. The most mentioned limitation was poor haptic feedback of the simulators, which was very important during the surgical training, since it is the key element for junior doctors to master practical procedures. Also, some simulators didn’t possess the integrated and elaborate structure as the human tissue, hence not the whole surgical procedures can be practiced by the trainees, and further improvement should be made. Although there are shortages, many studies have proved that 3D printing simulator can effectively reduce learning curves and is useful to enhance the trainees’ surgical skills.
Development of capillary dysfunction in Alzheimer’s disease
Authors: Vorobev S. , Yanishevskiy S. , Efimtsev S. , Sokolov A. , Dyachuk V.
Published: August 2024

Alzheimer’s disease (AD) is currently considered the major cause of cognitive impairment in older adults. This explains the close attention to the issue of AD research. The pathomorphological basis of the disease is a neurodegenerative process, the early stages of which are formed in the hippocampus and the morphofunctionally deep parts of the temporal lobes of the brain closely related to it. Several hypotheses have been advanced concerning the causes of neurodegeneration: the amyloid hypothesis, the calcium homeostasis impairment hypothesis, the inflammatory hypothesis, and the prion hypothesis. However, these hypotheses cannot explain the early stages of the pathogenesis of neurodegenerative diseases, in particular Alzheimer’s disease. This health problem requires further comprehensive study of available data, as well as additional investigations to determine the nature of such a process. In this review, the data on microcirculatory disorders in the capillaries of the hippocampus and mediobasal structures of the temporal lobes of the brain, which may be an initiating factor that triggers neurodegenerative events, are analyzed.
Acute medications’ intake for migraine: a one-year report in patients undergoing first evaluation at a third level Italian headache center
Authors: Bonura Adriano , Alesina Alessandro , Sapio Elisabetta , Brunelli Nicoletta , Marcosano Marilena , Altamura Claudia , Vernieri Fabrizio
Published: August 2024

Background

Headache disorders, particularly primary headaches like migraine and tension-type headache, still remain underdiagnosed and undertreated despite their high prevalence and significant impact on quality of life. In recent years, several specific medications targeting key pathways in the pathophysiology of migraine have been developed. Despite this advancement, numerous studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics remain the most commonly used drugs. This study focused on the use of NSAIDs and simple analgesics as acute treatments for migraine among patients at a tertiary headache center.

Methods

A retrospective observational study was conducted at the Fondazione Policlinico Universitario Campus Bio-Medico throughout 2022. Data were collected on the type and frequency of headaches, the usage and dosage of NSAIDs and other medications, and changes in their use at follow-up visits. Statistical analyses were performed to evaluate the efficacy and determinants of NSAID consumption and headache frequency changes.

Results

Two hundred and eightythree patients diagnosed with migraine undergoing their first examination at our center were enrolled. Initially, 58.7% of patients used NSAIDs or simple analgesics, which decreased to 46.6% 3 months after, while triptan use increased from 65.1 to 72.8%. Changes in prophylactic therapies were significantly associated with a decrease in NSAID intake (W = 834.000, p = 0.004) and in headache frequency (W = 5960.5, p = 0.003). Specifically, the addition of topiramate or amitriptyline was associated with a reduction in NSAID use and headache frequency. Even pain freedom after the intake of NSAIDs improved from 55.2 to 79.4% of cases at follow-up.

Conclusion

The study highlights the importance of appropriate diagnosis and tailored treatment strategies in the management of primary headaches. It underscores the need for specialized care to enhance treatment efficacy and patient outcomes, demonstrating that adjustments in prophylactic therapy can significantly reduce NSAID intake and improve headache care. This reinforces the role of tertiary headache centers in providing specialized care that can adapt treatments to individual patient needs and improve overall headache management.
A response time model of the three-choice Mnemonic Similarity Task provides stable, mechanistically interpretable individual-difference measures
Authors: Banavar Nidhi V. , Noh Sharon M. , Wahlheim Christopher N. , Cassidy Brittany S. , Kirwan C. Brock , Stark Craig E. L. , Bornstein Aaron M.
Published: August 2024

Introduction

The Mnemonic Similarity Task (MST) is a widely used measure of individual tendency to discern small differences between remembered and presently presented stimuli. Significant work has established this measure as a reliable index of neurological and cognitive dysfunction and decline. However, questions remain about the neural and psychological mechanisms that support performance in the task.

Methods

Here, we provide new insights into these questions by fitting seven previously-collected MST datasets (total N = 519), adapting a three-choice evidence accumulation model (the Linear Ballistic Accumulator). The model decomposes choices into automatic and deliberative components.

Results

We show that these decomposed processes both contribute to the standard measure of behavior in this task, as well as capturing individual variation in this measure across the lifespan. We also exploit a delayed test/re-test manipulation in one of the experiments to show that model parameters exhibit improved stability, relative to the standard metric, across a 1 week delay. Finally, we apply the model to a resting-state fMRI dataset, finding that only the deliberative component corresponds to off-task co-activation in networks associated with long-term, episodic memory.

Discussion

Taken together, these findings establish a novel mechanistic decomposition of MST behavior and help to constrain theories about the cognitive processes that support performance in the task.
A transporter’s doom or destiny: SLC6A1 in health and disease, novel molecular targets and emerging therapeutic prospects
Authors: Shah Nikita , Kasture Ameya S. , Fischer Florian P. , Sitte Harald H. , Hummel Thomas , Sucic Sonja
Published: August 2024

As the first member of the solute carrier 6 (SLC6) protein family, the γ-aminobutyric acid (GABA) transporter 1 (GAT1, SLC6A1), plays a pivotal role in the uptake of GABA from the synaptic cleft into neurons and astrocytes. This process facilitates the subsequent storage of GABA in presynaptic vesicles. The human SLC6A1 gene is highly susceptible to missense mutations, leading to severe clinical outcomes, such as epilepsy, in the afflicted patients. The molecular mechanisms of SLC6A1-associated disorders are discerned to some degree; many SLC6A1 mutations are now known to impair protein folding, and consequently fail to reach the plasma membrane. Inherently, once inside the endoplasmic reticulum (ER), GAT1 abides by a complex cascade of events that enable efficient intracellular trafficking. This involves association with specialized molecular chaperones responsible for steering the protein folding process, oligomerization, sorting through the Golgi apparatus, and ultimately delivery to the cell surface. The entire process is subject to stringent quality control mechanisms at multiple checkpoints. While the majority of the existing loss-of-function SLC6A1 variants interfere with folding and membrane targeting, certain mutants retain abundant surface expression. In either scenario, suppressed GAT1 activity disrupts GABAergic neurotransmission, preceding the disease manifestation in individuals harboring these mutations. The nervous system is enthralling and calls for systematic, groundbreaking research efforts to dissect the precise molecular factors associated with the onset of complex neurological disorders, and uncover additional non-canonical therapeutic targets. Recent research has given hope for some of the misfolded SLC6A1 variants, which can be salvaged by small molecules, i.e., chemical and pharmacological chaperones, acting on multiple upstream targets in the secretory pathway. We here highlight the significance of pharmacochaperoning as a therapeutic strategy for the treatment of SLC6A1-related disorders.