bluuebunny/crossref_metadata_2025 huggingface dataset:
The Dynamics between the Orthodox Tewahedo Church and Polity in Modern Ethiopia and Its Role in Establishing Peace in the Country
Authors: Jacob Ponodath Jossi
Published: July 2024

The interaction between the Orthodox Church and the state in Ethiopia has undergone various phases throughout the country's history. Emperor Haile Selassie, who came to power in 1930, sought to modernise Ethiopia by adopting Western educational and administrative systems. This included restructuring the Church administration to establish a centralised hierarchy for easier control. The military regime that seized power in 1974, inspired by Marxist and Leninist ideologies, showed strong hostility towards religion. When this regime took over the Patriarchate in Addis Ababa, Church administration shifted back to influential monasteries in rural Ethiopia, leading to a period of reduced activity, often termed hibernation. Communist propaganda which aimed at secularising the urban youth population gained some traction until the regime's overthrow in 1991 following the collapse of the USSR. The quasi-democratic regime of the Ethiopian People's Revolutionary Democratic Front, which took power in 1991–92, liberated all religious communities from political suppression. They introduced an ethnic federalism system, dividing the country into states based on ethnicity. However, this regime later faced accusations of favouring a single ethnic group, leading to the rise of the current oligarchical government in 2017. Consequently, the Orthodox Church saw a decline in its political influence. This paper examines these historical and political developments in relation to Church history to understand the Ethiopian Orthodox Church's role in past, present and future peace restoration efforts, particularly following recent conflicts in northern Ethiopia.
How Churches Can Become Trapped by Violence and Hatred: The Example of Italy in Ethiopia
Authors: Binns John
Published: July 2024

During the Italian occupation of Ethiopia between 1935 and 1941 there was an outbreak of brutal and violent attacks on the Ethiopian church. These attacks were supported by many in the Italian church and were described as a Crusade, with no condemnation of them from the papacy. The two churches come from very different geographical locations and cultural backgrounds, and this has led to periods of warm relations, but also to examples of aggressive evangelism and hostility. The situation at the start of the Second World War aggravated aggressive tendencies. They are a warning to the churches of how easy it is to slip into violence and hatred.
Tarih Boyunca Birgi ve Mahallelerinin Gelişimi ile Yeryüzü Şekillerinin Etkisi
Authors: Kaya Didem Sevtap , Vardar Serdar , Kara Emre
Published: July 2024

Birgi Bozdağlar’ın güney eteklerinde bulunan bir birikinti konisi üzerinde yer alan en az 5500 yıllık tarihi ve görkemli başkentlik dönemi ile önemli bir kadim kenttir. Yerleşim, birikinti konisinin engebeli yüzeyine ve bunu derince yarmış derelerin kenarlarına kurulmuştur. Küçük Menderes Havzası içinde kalan kent, bu alanda var olmuş; Tunç Çağı, Roma, Lidya, Bizans, Aydınoğlu Beyliği ve Osmanlı döneminin izlerini özgün doğal-kültürel dokusu içinde günümüze kadar saklamıştır. İlk yerleşimden günümüze kadar gelişen kent ve mahalleleri kentsel dokunun yeryüzü şekillerinin kontrolünde geliştiğini ortaya koymaktadır. Bu çalışmada söz konusu gelişimin açıklanması için tarihi belge ve yayınlardan yola çıkarak mahalle ve nüfus gelişimi araştırılmıştır. Diğer yandan koni morfometrisi üzerine jeomorfolojik saha çalışmaları yapılmıştır. Böylece Birgi Kenti ve mahallelerinin gelişiminin birikinti konisinin morfolojisi ile ilişkileri tüm detayları ile ortaya konulmuştur.
Unveiling the Dynamics: Exploring the Relationship between Emerging Stock Market Prices and Macroeconomic Factors through ARDL Analysis
Authors: Gümüş Nihat , Baba Murtala Mustapha
Published: July 2024

This study investigates the interaction between stock prices and prices in other markets using a panel ARDL model. Analyzing data from January 2004 to December 2022 for 19 emerging market countries, the study explores the impacts of gold prices, exchange rates, inflation rates, and interest rates on stock prices. The results indicate a long-term negative relationship, except for gold, between the variables. The effects are generally insignificant in the short run, except for gold's negative impact. The global financial crisis of 2008 negatively affected emerging market stock markets in both the short and long term. In the short run, the COVID-19 pandemic negatively impacted stock market returns, which turned positive in the long run. This study highlights the importance of sound monetary policies focused on price stability and fiscal policies aimed at reducing government dominance in financial markets to foster long-term growth in stock markets.
Collateral flow and pulsatility during large vessel occlusions: insights from a quantitative in vitro study
Authors: Luisi Claudio A. , Nikoubashman Omid , Steinseifer Ulrich , Wiesmann Martin , Neidlin Michael
Published: July 2024

Acute ischemic stroke caused by large vessel occlusions is being increasingly treated with neurovascular interventions. The hemodynamics within the collateral system of the circle of Willis (CoW) hemodynamics play a fundamental role in therapy success. However, transient in vivo data on pathological collateral flow during large vessel occlusions are not available. Moreover, there are no flow models that accurately simulate the hemodynamic conditions in the CoW during large vessel occlusions. We used a circulatory loop to generate highly reproducible cerebrovascular-like flows and pressures and used non-invasive flow visualization and high-resolution flow and pressure measurements to acquire detailed, time-dependent hemodynamics inside an anatomical phantom of the CoW. After calibrating a physiological reference case, we induced occlusions in the 1. middle cerebral artery, 2. terminal carotid artery, and 3. basilar artery; and measured the left posterior communicating artery flow. Mean arterial pressure and pulse pressure remained unchanged in the different occlusion cases compared to the physiological reference case, while total cerebral flow decreased by up to 19%. In all three occlusion cases, reversed flow was found in the left posterior communicating artery compared to the reference case with different flow magnitudes and pulsatility index values. The experimental results were compared with clinical findings, demonstrating the capability of this realistic cerebrovascular flow setup. This novel cerebrovascular flow setup opens the possibility for investigating different topics of neurovascular interventions under various clinical conditions in controlled preclinical laboratory studies.
RhoGDI1 regulates cell-cell junctions in polarized epithelial cells
Authors: Wibbe Nicolina , Steinbacher Tim , Tellkamp Frederik , Beckmann Niklas , Brinkmann Frauke , Stecher Manuel , Gerke Volker , Niessen Carien M. , Ebnet Klaus
Published: July 2024

Cell-cell contact formation of polarized epithelial cells is a multi-step process that involves the co-ordinated activities of Rho family small GTPases. Consistent with the central role of Rho GTPases, a number of Rho guanine nucleotide exchange factors (GEFs) and Rho GTPase-activating proteins (GAPs) have been identified at cell-cell junctions at various stages of junction maturation. As opposed to RhoGEFs and RhoGAPs, the role of Rho GDP dissociation inhibitors (GDIs) during cell-cell contact formation is poorly understood. Here, we have analyzed the role of RhoGDI1/ARHGDIA, a member of the RhoGDI family, during cell-cell contact formation of polarized epithelial cells. Depletion of RhoGDI1 delays the development of linear cell-cell junctions and the formation of barrier-forming tight junctions. In addition, RhoGDI1 depletion impairs the ability of cells to stop migration in response to cell collision and increases the migration velocity of collectively migrating cells. We also find that the cell adhesion receptor JAM-A promotes the recruitment of RhoGDI1 to cell-cell contacts. Our findings implicate RhoGDI1 in various processes involving the dynamic reorganization of cell-cell junctions.
Integrated analysis of gut microbiome and its metabolites in ACE2-knockout and ACE2-overexpressed mice
Authors: Song Lini , Ji Wenyi , Cao Xi
Published: July 2024

Background

Aberrant activation of the classic renin–angiotensin system (RAS) and intestinal micro dysbiosis adversely affect insulin resistance (IR), dyslipidemia, and other metabolic syndrome markers. However, the action of angiotensin-converting enzyme 2 (ACE2) and gut health in systemic homeostasis vary, and their interaction is not completely understood.

Methods

We adopted a combinatory approach of metabolomics and fecal 16S rRNA analysis to investigate gut microbiota and metabolite in two different mouse models, ACE2 knockout (ACE2 KO) mice and the ACE2-overexpressing obese mice.

Results

16S rRNA gene sequencing revealed that ACE2 influences microbial community composition and function, and ACE2 KO mice had increased Deferribacteres, Alcaligenaceae, Parasutterella, Catenibacterium, and Anaerotruncus, with decreased short-chain fatty acid (SCFA)-producing bacteria (Marvinbryantia and Alistipes). In contrast, ACE2-overexpressed mice exhibited increased anti-inflammatory probiotic (Oscillospiraceae, Marinifilaceae, and Bifidobacteriaceae) and SCFA-producing microbes (Rikenellaceae, Muribaculaceae, Ruminococcaceae, Odoribacter, and Alistipes) and decreased Firmicutes/Bacteroidetes, Lactobacillaceae, Erysipelotrichaceae, and Lachnospiraceae. Metabolome analysis indicated differential metabolites in ACE2 KO and ACE2-overexpression mice, especially the glucolipid metabolism-related compounds. Furthermore, correlation analysis between gut microbiota and metabolites showed a dynamic mutual influence affecting host health.

Conclusion

Our study confirms for the first time a significant association between ACE2 status and gut microbiome and metabolome profiles, providing a novel mechanism for the positive effect of ACE2 on energy homeostasis.
Projections of the Adriatic wave conditions under climate changes
Authors: Moulin Aimie , Mentaschi Lorenzo , Clementi Emanuela , Verri Giorgia , Mercogliano Paola
Published: July 2024

Assessing the impact of climate change on wave conditions, including average and extreme waves, is vital for numerous marine-related activities, industries, coastal vulnerability, and marine habitats. Previous research, primarily on a large scale, has investigated this topic, but its relevance for marginal basins like the Adriatic Sea is limited due to the low resolution of the wave models used and atmospheric forcing. To contribute to filling in the gap, here we implemented a high-resolution model (about 2 km) for the period 1992–2050. The future wave climate is simulated for the RCP8.5 emission scenario. This model, developed within the AdriaClim project, comprises, among others, a high-resolution atmospheric downscaling, a circulation Limited Area Model and a spectral wave model. A comparison of our simulation's results with Copernicus Marine Service wave reanalysis on the historical baseline, confirms its accuracy in reproducing both average wave parameters and 95th percentile values, as well as the seasonal cycle, showing the AdriaClim model's suitability as a source to predict future wave climates in the Adriatic Sea. The projected changes suggest a slight increase in average significant wave height and mean wave period, and a more significant decrease at the 95th percentile, with a relevant variability by location and season, partially aligning with previous studies. This study highlights the potential effect of local climate change in coastal areas and the importance of developing long-term simulation with a downscaled modeling system for regional areas.
The risk of ovarian cancer in hormone replacement therapy users: a systematic review and meta-analysis
Authors: Xiang Hongqin , Wang Liangying , Sun Liping , Xu Song
Published: July 2024

Background

With the increasing use of hormone replacement therapy (HRT), there is a need to understand its impact on the occurrence of female malignant tumors. This systematic review and meta-analysis aimed to assess the risk of ovarian cancer associated with HRT and its related risk factors.

Methods

PUBMED, OVID, Embase, Cochrane, and Web of Science were searched from 1980 to April 2022 to identify studies on the risk of ovarian cancer and hormone replacement therapy. The random-effects model was used to estimate the pooled risk of HRT in ovarian cancer, both in cohort studies and case-control studies. Additionally, the analysis examined the outcomes associated with different types of estrogen plus progesterone regimens. Meta-regression and sensitive analysis were performed to evaluate the heterogeneity.

Results

21 cohort studies (involving 15,313 cases and 4,564,785 participants) and 30 case-control studies (including 18,738 cases and 57,747 controls) were analyzed. The pooled risks of ovarian cancer for HRT users were 1.20 (95% confidence interval [CI] 1.01–1.44) from cohort studies and 1.13 (95%CI 1.04–1.22) from case-control studies. However, after restricting the study period to recent decades, the significant results indicating a higher risk disappeared in cohort studies conducted after 2010 and in case-control studies conducted after 2006. Furthermore, the continuous use of estrogen-progesterone replacement therapy (EPRT) was associated with a risk comparable to that of sequential use. Subgroup analysis showed that both estrogen replacement treatment (ERT) and EPRT had minor risks; The risk further increased with prolonged exposure time, particularly for durations exceeding 10 years. Additionally, serous ovarian cancer appeared to be more susceptible than other pathological types.

Conclusion

The risk of ovarian cancer associated with HRT has been decreasing over time. However, ERT may increase this risk, particularly when used for an extended period. It is recommended that long-time users consider continuous EPRT as a safer alternative.

Systematic review registration

www.crd.york.ac.uk/prospero/, identifier CRD42022321279.
Integrative single-cell analysis of longitudinal t(8;21) AML reveals heterogeneous immune cell infiltration and prognostic signatures
Authors: Li Xue-Ping , Song Jiang-Tao , Dai Yu-Ting , Zhang Wei-Na , Zhao Bai-Tian , Mao Jia-Ying , Gao Yan , Jiang Lu , Liang Yang
Published: July 2024

Introduction

Immunotherapies targeting T cells in solid cancers are revolutionizing clinical treatment. Novel immunotherapies have had extremely limited benefit for acute myeloid leukemia (AML). Here, we characterized the immune microenvironment of t(8;21) AML patients to determine how immune cell infiltration status influenced prognosis.

Methods

Through multi-omics studies of primary and longitudinal t(8;21) AML samples, we characterized the heterogeneous immune cell infiltration in the tumor microenvironment and their immune checkpoint gene expression. Further external cohorts were also included in this research.

Results

CD8+ T cells were enriched and HAVCR2 and TIGIT were upregulated in the CD34+CD117dim%-High group; these features are known to be associated with immune exhaustion. Data integration analysis of single-cell dynamics revealed that a subset of T cells (cluster_2) (highly expressing GZMB, NKG7, PRF1 and GNLY) evolved and expanded markedly in the drug-resistant stage after relapse. External cohort analysis confirmed that the cluster_2 T-cell signature could be utilized to stratify patients by overall survival outcome.

Discussion

In conclusion, we discovered a distinct T-cell signature by scRNA-seq that was correlated with disease progression and drug resistance. Our research provides a novel system for classifying patients based on their immune microenvironment.
Biological and fishery indicators for the small-scale marble crab fishery in Northern Patagonia: recommendations for improving a monitoring program and stock assessment of a data-limited fishery
Authors: Hamamé Madeleine , Aedo Gustavo , Ortiz Paula , Olguín Andrés , Pardo Luis Miguel
Published: July 2024

Small-scale fisheries have been typically data-limited despite their economic importance for local communities. This is especially true in zones where fishing operations occur in remote areas under harsh weather conditions. Crab fishery in Chile is exclusively artisanal, and marble crab (Metacarcinus edwardsii) has the highest landing records. This species is found in most parts of the coast of Chile, but it is mainly caught in the south of the country (including Patagonia). Fishery management is data-limited, and monitoring has not established the spatial and temporal variability baseline necessary to determine its exploitation status. This fishery is currently evaluated annually under a scheme based on reporting biological and fishery information, primarily from the landing ports and secondarily from fishing grounds. In the present study, we collected data from fishing grounds on board artisanal fishing vessels around 45°S during an annual cycle to establish indicators based on catch per unit effort (above and below minimum legal size), size, sex ratio, and the relationship between weight and size. Our results showed that fishery and biological indicators respond more to seasonal patterns than to expected spatial heterogeneity related to different fishing grounds: proportional stock density (lowest in winter), sex ratio (biased toward males in winter), retained catch (highest in autumn), and released catch (highest in winter), while the average size of the largest 10% of the sample only showed differences between males and females. Additionally, released catch varied according to soak time, which indicates the effectiveness of escape rings incorporated in the traps. These results lead to recommendations related to the current monitoring program, which should include the selection of a limited number of fishing grounds standardized by season and the incorporation of information related to soak time and the presence of escape rings. Finally, this study highlights the importance of on-board scientific monitoring for any fisheries, even those of small scale.
Developing a clinical-pathological framework of long COVID-related fatigue applied to public safety workers
Authors: Lofrano-Porto Adriana , D’Isabel Susanne , Smith Denise L.
Published: July 2024

In the wake of the COVID-19 pandemic, millions worldwide are still struggling with persistent or recurring symptoms known as long COVID. Fatigue is one of the most prevalent symptoms associated with long COVID, and for many it can be debilitating. Understanding the potential pathological processes that link fatigue to long COVID is critical to better guide treatment. Challenges with diagnosis and treatment are reviewed, recognizing that post-COVID fatigue does not always present with corroborating clinical evidence, a situation that is frustrating for both patients and healthcare providers. Firefighters are a group of public safety workers who are particularly impacted by long COVID-related fatigue. Firefighters must be able to engage in strenuous physical activity and deal with demanding psychological situations, both of which may be difficult for those suffering from fatigue. Disruption in public safety worker health can potentially impact community welfare. This review creates a framework to explain the clinical-pathological features of fatigue resulting from long COVID, addresses diagnosis and treatment challenges, and explores the unique impact fatigue may pose for public safety workers and their organizations.
Adenomatous hyperplasia induced by chronic cherry pit retention mimicking an endobronchial tumor-case series and systematic review of literature
Authors: Oruqaj Gani , Krombach Gabriele , Gattenloehner Stefan , Herold Susanne , Vadász István , Seeger Werner , Tello Khodr , Hecker Matthias
Published: July 2024

Introduction

Endobronchial foreign body aspiration is not common in adults, but it is a life-threatening event. Recurrent pneumonias by chronic retention of foreign body often lead to initial medical presentation of the patient. However, lymphoplasmacellular bronchitis with adenomatous hyperplasia and squamous epithelium metaplasia with complete or partial blockage of lobar bronchus mimicking lung tumor is rare in literature, and this particular condition is often misdiagnosed.

Case presentation

we report our experience in the diagnostic and management of two elderly patients with recurrent pneumonia, admitted in hospital for further examination. In both patients, with no history of aspiration, the cherry pit was detected during bronchoscopy and recanalization with flexible cryoprobe, surrounded by purulent secretion, occluding completely the right upper lobe in the first case, and partially the left lower lobe associated with persistent actinomycosis in the second case, with signs of local inflammation, bronchial adenomatous hyperplasia mimicking lung tumor at initial bronchoscopic examination. Histology showed a lymphoplasmacellullar bronchitis with adenomatous hyperplasia and squamous epithelium metaplasia because of chronic retention of foreign body.

Conclusion

Bronchoscopy examination should be considered in cases where there is an unresolved chronic cough with recurrent pneumonia or persistent actinomycosis in patients with high risk. Cryoprobe is a safe and feasible approach for treatment of airway obstructions due to chronic foreign body retention. Furthermore, relevant findings are discussed here, along with a review of the pathologic alterations and treatment modalities seen in chronic retention of foreign body and airway injury.
Assessing the credibility of a drug’s effects: identification and judgment of uncertainty by the Dutch Medicines Evaluation Board
Authors: Hoek Joyce M. , Brenninkmeijer Jonna , de Vries Ymkje Anna , Meijer Rob R. , van Ravenzwaaij Don
Published: July 2024

Medicine regulators need to judge whether a drug’s favorable effects outweigh its unfavorable effects based on a dossier submitted by an applicant, such as a pharmaceutical company. Because scientific knowledge is inherently uncertain, regulators also need to judge the credibility of these effects by identifying and evaluating uncertainties. We performed an ethnographic study of assessment procedures at the Dutch Medicines Evaluation Board (MEB) and describe how regulators evaluate the credibility of an applicant’s claims about the benefits and risks of a drug in practice. Our analysis shows that regulators use an investigative approach, which illustrates the effort required to identify uncertainties. Moreover, we show that regulators’ expectations about the presentation, the design, and the results of studies can shape how they perceive a medicine’s dossier. We highlight the importance of regulatory experience and expertise in the identification and evaluation of uncertainties. In light of our observations, we provide two recommendations to reduce avoidable uncertainty: less reliance on evidence generated by the applicant; and better communication about, and enforcement of, regulatory frameworks toward drug developers.
Venetoclax combined with azacitidine in blastic plasmacytoid dendritic cell neoplasm: a case report and comprehensive review on the current and future treatment
Authors: Wang Xiaoning , Guo Jiashuo , Liu Yan , Zheng Na , Xu Shaohan , Wu Lianhui , Yuan Ruirui , Xue Liying , Li Jie
Published: July 2024

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare hematological malignancy with a highly aggressive behavior and median survival of <2 years. Especially, most BPDCN patients present with extensive and non-specific skin lesions, usually leading to misdiagnosis as a skin disease and delay therapy. As for treatment, most patients with BPDCN experience relapse shortly after treatment with the traditional regimens. The alleviation of skin symptoms reflects the effects of clinical treatments. Herein, we report a case of a 71-year-old man with intermittent and gradually expanding skin lesions over his chest, abdomen, and back for 1 year. On admission, physical examination revealed extensive skin lesions and multiple enlarged lymph nodes. Laboratory examinations showed pancytopenia and numerous malignant cells in the peripheral blood smear (60%), bone marrow aspirate smear (73.5%). Immunophenotyping using flow cytometry and immunohistochemistry presented large numbers of BPDCN cells in the bone marrow, cervical lymph nodes and dermal tissue. PET/CT revealed multiple enlarged lymph nodes and splenomegaly. Once the diagnosis was identified as BPDCN, the patient began treatment with the oral BCL2 inhibitor venetoclax and subcutaneously administered azacitidine. After the first course, skin lesions reduced markedly and complete remission was achieved in the bone marrow. Our study and current cumulative data according to reviewing systematically suggest that venetoclax combined with azacitidine is safe, effective, and applicable in the treatment of BPDCN, especially for elderly relapsed/refractory patients. This study, therefore, significantly contributes to the literature on the current and future treatment for BPDCN.
Antimicrobial non-porous surfaces: a comparison of the standards ISO 22196:2011 and the recently published ISO 7581:2023
Authors: Maitz Stephanie , Poelzl Sabine , Dreisiebner Daniela , Zarschenas Eva , Kittinger Clemens
Published: July 2024

The application of antimicrobial surfaces requires the proof of their effectivity by in vitro methods in laboratories. One of the most well-known test methods is ISO 22196:2011, which represents a simple and inexpensive protocol by applying the bacterial suspension with known volume and concentration covered under a polyethylene film on the surfaces. The incubation is then done under defined humidity conditions for 24 h. Another approach for testing of non-porous surfaces is the newly published ISO 7581:2023. A “dry test” is achieved through spreading and drying 1 μL of a bacterial suspension on the surface. In this study, low alloyed carbon steel, polyethylene terephthalate (PET), and glass specimens were tested uncoated (reference) and coated with zinc according to both ISOs to compare and to evaluate the advantages and disadvantages of each one of them. Although ISO 7581:2023 allows a more realistic test environment than ISO 22196:2011, the reproducibility of the results is not given due to the low application volume. In addition, not all bacterial strains are equally suitable for this testing type. Individual adaptations to the protocols, including incubation conditions (time, temperature, or relative humidity), testing strains and volume, seem necessary to generate conditions that simulate the final application. Nevertheless, both ISOs, if used correctly, provide a good basis for estimating the antimicrobial efficacy of non-porous surfaces.
Melittin alcalase-hydrolysate: a novel chemically characterized multifunctional bioagent; antibacterial, anti-biofilm and anticancer
Authors: El-Didamony Samia E. , Kalaba Mohamed H. , Sharaf Mohamed H. , El-Fakharany Esmail M. , Osman Ali , Sitohy Mahmoud , Sitohy Basel
Published: July 2024

The prevalent life-threatening microbial and cancer diseases and lack of effective pharmaceutical therapies created the need for new molecules with antimicrobial and anticancer potential. Bee venom (BV) was collected from honeybee workers, and melittin (NM) was extracted from BV and analyzed by urea-polyacrylamide gel electrophoresis (urea-PAGE). The isolated melittin was hydrolyzed with alcalase into new bioactive peptides and evaluated for their antimicrobial and anticancer activity. Gel filtration chromatography fractionated melittin hydrolysate (HM) into three significant fractions (F1, F2, and F3), that were characterized by electrospray ionization mass spectrometry (ESI-MS) and evaluated for their antimicrobial, anti-biofilm, antitumor, and anti-migration activities. All the tested peptides showed antimicrobial and anti-biofilm activities against Gram-positive and Gram-negative bacteria. Melittin and its fractions significantly inhibited the proliferation of two types of cancer cells (Huh-7 and HCT 116). Yet, melittin and its fractions did not affect the viability of normal human lung Wi-38 cells. The IC50 and selectivity index data evidenced the superiority of melittin peptide fractions over intact melittin. Melittin enzymatic hydrolysate is a promising novel product with high potential as an antibacterial and anticancer agent.
Next generation plant biostimulants & genome sequencing strategies for sustainable agriculture development
Authors: Garg Shivanshu , Nain Pooja , Kumar Ashish , Joshi Samiksha , Punetha Himanshu , Sharma Pradeep Kumar , Siddiqui Sazada , Alshaharni Mohammed O. , Algopishi Uthman Balgith , Mittal Amit
Published: July 2024

The best environment for plant growth and development contains certain essential metabolites. A broad category of metabolites known as “plant biostimulants” (PBs) includes biomolecules such as proteins, carbohydrates, lipids, and other secondary metabolites related to groups of terpenes, specific nitrogen-containing compounds, and benzene ring-conjugated compounds. The formation of biomolecules depends on both biotic and abiotic factors, such as the release of PB by plants, animals, and microorganisms, or it can result from the control of temperature, humidity, and pressure in the atmosphere, in the case of humic substances (HSs). Understanding the genomic outputs of the concerned organism (may be plants or others than them) becomes crucial for identifying the underlying behaviors that lead to the synthesis of these complex compounds. For the purposes of achieving the objectives of sustainable agriculture, detailed research on PBs is essential because they aid in increasing yield and other growth patterns of agro-economic crops. The regulation of homeostasis in the plant-soil-microbe system for the survival of humans and other animals is mediated by the action of plant biostimulants, as considered essential for the growth of plants. The genomic size and gene operons for functional and regulation control have so far been revealed through technological implementations, but important gene annotations are still lacking, causing a delay in revealing the information. Next-generation sequencing techniques, such as nanopore, nanoball, and Illumina, are essential in troubleshooting the information gaps. These technical advancements have greatly expanded the candidate gene openings. The secondary metabolites being important precursors need to be studied in a much wider scale for accurate calculations of biochemical reactions, taking place inside and outside the synthesized living cell. The present review highlights the sequencing techniques to provide a foundation of opportunity generation for agricultural sustainability.
Stress-induced anxiety-related behavior in mice is driven by enhanced excitability of ventral tegmental area GABA neurons
Authors: Mitten Eric H. , Souders Anna , Marron Fernandez de Velasco Ezequiel , Wickman Kevin
Published: July 2024

Introduction

Stress and trauma are significant risk factors for many neuropsychiatric disorders and diseases, including anxiety disorders. Stress-induced anxiety symptoms have been attributed to enhanced excitability in circuits controlling fear, anxiety, and aversion. A growing body of evidence has implicated GABAergic neurons of the ventral tegmental area (VTA) in aversion processing and affective behavior.

Methods

We used an unpredictable footshock (uFS) model, together with electrophysiological and behavioral approaches, to investigate the role of VTA GABA neurons in anxiety-related behavior in mice.

Results

One day after a single uFS session, C57BL/6J mice exhibited elevated anxiety-related behavior and VTA GABA neuron excitability. The enhanced excitability of VTA GABA neurons was correlated with increased glutamatergic input and a reduction in postsynaptic signaling mediated via GABAA and GABAB receptors. Chemogenetic activation of VTA GABA neurons was sufficient to increase anxiety-related behavior in stress-naïve mice. In addition, chemogenetic inhibition of VTA GABA neurons suppressed anxiety-related behavior in mice exposed to uFS.

Discussion

These data show that VTA GABA neurons are an early substrate for stress-induced anxiety-related behavior in mice and suggest that approaches mitigating enhanced excitability of VTA GABA neurons may hold promise for the treatment of anxiety provoked by stress and trauma.
Stiff-person syndrome in association with Hashimoto’s thyroiditis: a case report
Authors: Chen Mingzhu , Hong Zhou , Shi Haicun , Wen Chunmei , Shen Yuan
Published: July 2024

Stiff-person syndrome (SPS) is a rare neurological disorder characterized by chronic and progressive axial muscle rigidity and paroxysmal painful muscle spasms. The present case study described an SPS patient (increased anti-GAD65 antibody in serum and cerebrospinal fluid) with co-occurring Hashimoto’s thyroiditis and decreased C3 complement levels. The clinical presentation, diagnostic approach, and treatment employed for this unique case were comprehensively described in detail. In this case, we comprehensively presented a case of SPS with co-occurring Hashimoto’s thyroiditis and an associated decrease in serum C3 complement, as well as a discussion on the current data on this topic.
Aberrant functional connectivity in anterior cingulate gyrus subregions in migraine without aura patients
Authors: Cheng Jinming , Li Yan , Chen Keyang , Cao Yungang , Liu Kun , Zhang Xi , Wu Xiaoyuan , Wang Zhihong , Liu Xiaozheng , Li Litao
Published: July 2024

Background

The anterior cingulate gyrus (ACG) is an important regulatory region for pain-related information. However, the ACG is composed of subregions with different functions. The mechanisms underlying the brain networks of different subregions of the ACG in patients with migraine without aura (MwoA) are currently unclear.

Methods

In the current study, resting-state functional magnetic resonance imaging (rsfMRI) and functional connectivity (FC) were used to investigate the functional characteristics of ACG subregions in MwoA patients. The study included 17 healthy volunteers and 28 MwoA patients. The FC calculation was based on rsfMRI data from a 3 T MRI scanner. The brain networks of the ACG subregions were compared using a general linear model to see if there were any differences between the two groups. Spearman correlation analysis was used to examine the correlation between FC values in abnormal brain regions and clinical variables.

Results

Compared with healthy subjects, MwoA patients showed decreased FC between left subgenual ACG and left middle cingulate gyrus and right middle temporal gyrus. Meanwhile, MwoA patients also showed increased FC between pregenual ACG and right angular gyrus and increased FC between right pregenual ACG and right superior occipital gyrus. The FC values between pregenual ACG and right superior occipital gyrus were significantly positively correlated with the visual analogue scale.

Conclusion

Disturbances of FC between ACG subregions and default model network and visual cortex may play a key role in neuropathological features, perception and affection of MwoA. The current study provides further insights into the complex scenario of MwoA mechanisms.
Relationships of omega-3 and omega-6 polyunsaturated fatty acids with esophageal diseases: a two-sample Mendelian randomization analysis
Authors: Chen Weiming , Chen Maohui , Huang Jin , Xie Qichang , Huang Yizhou , Chen Chun , Zhu Yong
Published: July 2024

Introduction

Omega-3 polyunsaturated fatty acids (PUFAs) have been widely studied and used as nutritional supplements because of their anti-inflammatory effects. Previous studies have shown an association between polyunsaturated fatty acids such as omega-3 and omega-6 PUFAs with the development of malignant tumors. However, the relationships of omega-3 and omega-6 PUFAs with esophageal diseases have not been characterized.

Methods

Mendelian randomization (MR) is a statistical method for identifying instrumental variables (IVs) from genome-wide association study (GWAS) data, and is associated with little confounding by environmental or other disease-related factors. We used genome-wide association study (GWAS) data from previously published studies on circulating concentrations of omega-3, omega-6, docosahexaenoic acid (DHA) and linoleic acid (LA), as well as esophageal cancer and other esophageal diseases, which were downloaded from the IEU OpenGwas database (https://gwas.mrcieu.ac.uk/) and the GWAS Catalog database (https://www.ebi.ac.uk/). The inverse variance-weighted approach was used as the principal analysis, and the MR–Egger and weighted median methods were used alongside. A series of sensitivity analyses were used to ensure the robustness of the causality estimates.

Results

We found that the circulating omega-3 PUFAs concentration was positively associated with esophageal cancer (p = 8 × 10−4), and circulating DHA concentration (the main component of omega-3 in food), was also positively associated with esophageal cancer (p = 2 × 10−2), but no significant association was found between circulating omega-6 PUFAs and esophageal cancer (p = 0.17), and circulating LA concentration (the main component of omega-6 in food), was also no significant associated with esophageal cancer (p = 0.32). We found no significant relationships of circulating omega-3 and omega-6 PUFAs concentration with four other esophageal diseases.

Conclusion

This study indicates that higher levels of circulating omega-3 PUFAs and DHA concentrations may be a risk factor for the development of esophageal cancer. Conversely, an increased omega-6/omega-3 ratio may serve as a protective factor against esophageal cancer. These findings have significant implications for the clinical application of omega-3 PUFAs and the prevention and treatment of esophageal cancer.
Pediatric respiratory pathogen dynamics in Southern Sichuan, China: a retrospective analysis of gender, age, and seasonal trends
Authors: Li Qing , Song Min , Hu Zhi , Ding Yinhuan , Huang Chengliang , Liu Jinbo
Published: July 2024

Objective

To address the research gap in the epidemiology of pediatric respiratory tract infections (RTIs) in Luzhou, Southern Sichuan, China, by analyzing respiratory pathogens in a large pediatric cohort from 2018 to 2021, covering the pre- and during-COVID-19 periods.

Methods

This study conducted a retrospective analysis of children with RTIs in Luzhou from July 2018 to January 2021. Strict exclusion criteria were applied to ensure an accurate representation of the pediatric population. Pathogen detection included viruses, bacteria, and atypical agents.

Results

Pathogens were identified in 52.8% of 12,546 cases. Viruses accounted for 32.2% of infections, bacteria for 29.8%, and atypical agents for 29.7%, with significant findings of Staphylococcus aureus, Moraxella catarrhalis, and Mycoplasma pneumoniae. Age-related analysis indicated a higher incidence of bacterial infections in infants and viral infections in preschool-aged children, with atypical pathogens being most prevalent in 3–5-year-olds. Gender-based analysis, adjusted for age, revealed similar overall pathogen presence; however, females were more susceptible to viral infections, while males were more prone to Streptococcus pneumoniae. Notably, there was an unusual increase in pathogen cases during spring, potentially influenced by behavioral changes and public health measures related to COVID-19. Co-infections were identified as a significant risk factor for the development of pneumonia.

Conclusion

The study provides essential insights into the epidemiology of respiratory pathogens in pediatric populations, emphasizing the need for healthcare strategies tailored to age, gender, and seasonality. The findings highlight the impact of environmental and public health factors, including COVID-19 measures, on respiratory pathogen prevalence, underscoring the importance of targeted diagnostic and treatment protocols in pediatric respiratory infections.
The role of metabolic memory in diabetic kidney disease: identification of key genes and therapeutic targets
Authors: Yang Tongyue , Feng Qi , Shao Mingwei , Pan Mengxing , Guo Feng , Song Yi , Huang Fengjuan , Linlin Zhao , Wang Jiao , Wu Lina , Qin Guijun , Zhao Yanyan
Published: July 2024

Diabetic kidney disease (DKD) is characterized by complex pathogenesis and poor prognosis; therefore, an exploration of novel etiological factors may be beneficial. Despite glycemic control, the persistence of transient hyperglycemia still induces vascular complications due to metabolic memory. However, its contribution to DKD remains unclear. Using single-cell RNA sequencing data from the Gene Expression Omnibus (GEO) database, we clustered 12 cell types and employed enrichment analysis and a cell‒cell communication network. Fibrosis, a characteristic of DKD, was found to be associated with metabolic memory. To further identify genes related to metabolic memory and fibrosis in DKD, we combined the above datasets from humans with a rat renal fibrosis model and mouse models of metabolic memory. After overlapping, NDRG1, NR4A1, KCNC4 and ZFP36 were selected. Pharmacology analysis and molecular docking revealed that pioglitazone and resveratrol were possible agents affecting these hub genes. Based on the ex vivo results, NDRG1 was selected for further study. Knockdown of NDRG1 reduced TGF-β expression in human kidney-2 cells (HK-2 cells). Compared to that in patients who had diabetes for more than 10 years but not DKD, NDRG1 expression in blood samples was upregulated in DKD patients. In summary, NDRG1 is a key gene involved in regulating fibrosis in DKD from a metabolic memory perspective. Bioinformatics analysis combined with experimental validation provided reliable evidence for identifying metabolic memory in DKD patients.
Association between oral contraceptives and cervical cancer: A retrospective case–control study based on the National Health and Nutrition Examination Survey
Authors: Guo Chong , Zhan Bo , Li Meng-Yuan , Yue Li , Zhang Chao
Published: July 2024

Background: Cervical cancer is the fourth most common cancer among females globally, with a high incidence and high mortality among females in developing countries. This retrospective case–control study aimed to investigate the association between oral contraceptives and cervical cancer, on which insufficient evidence still exists.

Material and Methods: To examine the association between oral contraceptives and cervical cancer based on 7,496 females aged over 20 years from the National Health and Nutrition Examination Survey, multivariable logistic regression conducted from 1999 to 2016 was used.

Results: Contraceptive use was positively associated with cervical cancer risk. In model 1 (unadjusted), a 195% increased risk of cervical cancer was observed among those who used oral contraceptives (odds ratio [OR] = 2.27, 95% confidence interval [CI] = 1.39–3.98, p = 0.002) compared to those who did not. In addition, the ORs for the exposed population were 1.74 (95% CI = 1.05–3.08, p = 0.041) and 1.93 (95% CI = 1.16–3.44, p = 0.017) in model 2 (adjusted for age, race, and body mass index [BMI]) and model 3 (adjusted for education level, ratio of family income to poverty, drinking status, smoking status, number of pregnancies, age at first sex, number of sexual partners, and whether to receive the human papillomavirus (HPV) vaccine in addition to model 2), respectively. Furthermore, subgroup analyses stratified by age, smoking status, BMI, age at first sex, number of sexual partners, and whether to receive the HPV vaccine also revealed that oral contraceptives were significantly associated with cervical cancer.

Conclusion: This study demonstrated that oral contraceptive use increased the risk of cervical cancer. In addition, the higher risk, including individuals older than 45 years, having a high BMI (≥30 kg/m2), being current smokers, and having more than five sexual partners, may contribute to the development of cervical cancer.
Platycodon D reduces obesity and non-alcoholic fatty liver disease induced by a high-fat diet through inhibiting intestinal fat absorption
Authors: Tang Xingkui , Yang Yi , Peng Wenxu , Xu Mengping , Fan Qitong , Li Feng , Zou Guorong , Zhu Jianlin
Published: July 2024

Background

Platycodin D (PD) has been reported to treat metabolic diseases, including non-alcoholic fatty liver disease. In addition, platycodin D has been reported to activate intestinal 5'AMP-activated protein kinase (AMPK) phosphorylation levels, thereby reducing lipid absorption. Therefore, the aim of this study is to explore whether PD activation of intestinal AMPK and reduced lipid absorption can improve non-alcoholic fatty liver disease.

Methods

Clean-grade male C57/BL mice were fed a high-fat diet (HFD) (containing 60% calories) for 16 weeks, and oral PD (10 mg/kg/day) was administered at the same time. The liver and intestines were the collected, and the intestines were tested. The expressions of lipid absorption genes (CD36, NPC1L1, and ApoB), the serum total triglyceride (TG) and total cholesterol (TC) levels in the intestines and livers, the fecal free fatty acid (FFA) levels, and the expression of AMPK phosphorylated proteins in the intestines were examined using Western blot analyses. The lipid distribution in the livers, intestines, and fat was detected using Oil Red O and hematoxylin and eosin (H&E) staining. A colon cancer cell line (Caco2) was used to confirm the effect of PD on the cellular lipid uptake in vitro. In addition, serum inflammatory factors and liver enzymes were measured to clarify the impact of PD on the circulation of metabolic syndrome. Leptin-deficient mice (OB) were then used to further explore the improvement of PD on body weight and blood lipids.

Results

PD had a very significant therapeutic or preventive effect on metabolic syndrome and fatty liver induced by a high-fat diet. PD improved body weight, insulin sensitivity, and glucose tolerance in mice fed a high-fat diet and also prevented non-alcoholic fatty liver disease, reduced blood lipid levels, and increased fecal lipid excretion. In addition, PD reduced lipid absorption by activating the intestinal AMPK protein, which may have involved the inhibition of the gene expression levels of intestinal lipid absorption genes (CD36, NPC1L1, and ApoB). The combined effect of these factors improved hepatic lipid accumulation and lipid accumulation in adipose tissue. It was further found that PD also improved the body weights and blood lipid levels of leptin-deficient mice (OB) mice.

Conclusion

PD had a very strong therapeutic effect on mice under a high-fat diet. PD reduced high-fat diet-induced obesity and non-alcoholic fatty liver disease by inhibiting intestinal fat absorption.