bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast Isolation and Purification of the Antidepressant Alkaloids Mesembrine and Mesembrenone From Mesembryanthemum tortuosum
Authors: Niekerk Suzanne Elaine Van , Malan Dorothea , Hamman Josias Hendrik , Kooy Frank van der
Published: January 2025

Mesembryanthemum tortuosum L., Aizoaceae, is a medicinal plant that has traditionally been used as mood elevator, stress reducer, analgesic, anxiolytic, and even a narcotic. The main activity is attributed to the mesembrine-type alkaloids, which have shown promise to provide pharmacologically and clinically antidepressant and anxiolytic effects. Due to the limited availability and cost of pure reference compounds of the main active chemical compounds of M. tortuosum, this study aimed to develop a fast purification method for mesembrine and mesembrenone from M. tortuosum. A simple acid-base extraction was used as the first semi-purification step, which was directly followed by semi-preparative HPLC purification as final step. This reduced the number of steps as previously reported. Analytical quantities of mesembrine and mesembrenone (chemical structures confirmed by NMR and MS) could be purified up to roughly 98% purity (as determined by HPLC) with the whole purification process from extraction to obtaining the pure compounds completed at the relatively short period of only four hours. A quick and simple method to purify the mesembrine-type alkaloids, mesembrine and mesembrenone, was developed which produced sufficient quantities for use in analytical and biological studies. This provides a cost-effective method to overcome the lack of pure reference compounds for M. tortuosum.
Hot and Hungry: High temperatures induce changes in leaf carbohydrate dynamics and sugar isotope fingerprints
Authors: Schuler Philipp , Didion-Gency Margaux , Vitali Valentina , Saurer Matthias , Oettli Manuela , Diao Haoyu , Buchmann Nina , Gessler Arthur , Lehmann Marco
Published: January 2025

Accurate predictions of vegetation responses to global warming require a precise understanding of physiological temperature responses. We investigated the effects of air temperature (10°C to 40°C) under constant low vapour pressure deficit and sufficient water supply on leaf-level gas exchange, chlorophyll fluorescence, non-structural carbohydrate (NSC) concentrations, and the hydrogen (δ2H) and oxygen (δ18O) isotopic composition of leaf water and leaf sugar in C3 trees, forbs, grasses, and one C4 grass. Rising temperatures significantly altered leaf physiology, NSC composition, and the leaf sugar isotopic composition. We observed a shift from starch to sugar above 30°C, indicating a preference for a more readily available carbohydrate, with a concomitant shift in the hydrogen isotopic composition of leaf sugar. Furthermore, we demonstrate for the first time the close relationship between carbohydrate metabolism and stable isotope fractionation, with 2H enrichment in leaf sugar with increasing temperature. Our results suggest that C3 plants may experience shifts in their carbon metabolism at temperatures above 30°C, which can be detected by δ2H of leaf sugar. Such carbon imbalances may reduce the resilience of C3 plants in an increasingly warming world.
Phylogenomics of crabs provides insights into their origin and evolution
Authors: Wang Zhongkai , Tang Boping , Li Yongxin , Wang Gang , Liu Hongyue , Liu Qiuning , Sun Yishan , Lu Xiang , Han Ge , Zhang Huabin , Hao Fei , Wang Zhengfei , Xu Biyang , Ng Ngan Kee , Li Haorong , Sun Yue , Jiang Hui , Xuan Fujun , Jiang Senhao , Shen Jiafei , Sun Hongying , She Shusheng , Dong Dong , Wang Kun , Li Xinzheng , Qiu Qiang , Wang Wen , Zhang Daizhen , Li Yuanning
Published: January 2025

Crabs encompass the infra-orders Brachyura and Anomura, collectively constitute the clade Meiura within order Decapoda. Despite their considerable diversity, genomic resources for crabs remain scarce, hindering our understanding of their phylogeny and genetic mechanisms underlying such unique traits as carcinization. To address these questions, here we sequenced genomes of 10 crab species covering all currently controversial taxonomies at section level. Our whole-genome phylogenetic results support Raninoida is closer to Eubrachyura rather than Dromiacea, challenging the traditional classifications. Notably, the freshwater crab subsection Potamoida, represented by S. planum, is found to be more closely related to subsection Thoracotremata than to Heterotremata as previously suggested, indicating that crab classification based solely on morphology may be misleading. Our results also clarify that the family Gecarcinidae should be classified into Thoracotremata, contrary to previous placements in Heterotremata. Comparative genomic analyses identified lineage-specific families related to crab traits, including ionotropic glutamate receptors, neurotransmitters, and energy metabolism. Additionally, transcriptomic studies of Chinese mitten crab larval stages suggest that some lineage-specific genes such as ghrA, and TCB2, may account for the prominent carcinization in brachyurans. This study not only significantly expands the genomic repository for crabs, but also provides insights into the phylogeny and trait evolution of crabs.
Adherence to Guideline-Directed Medical Therapy in Heart Failure with Reduced Ejection Fraction: A Comparison Between Residents and Attending Physicians
Authors: Mohammadi Abbas , Youssef Ibrahim , Kobita Iryna , Hazhir-Karzar Nazanin , Akhondi Hossein A , Spaccavento Leo
Published: January 2025

Background
Heart failure with reduced ejection fraction (HFrEF) requires adherence to guideline-directed medical therapy (GDMT) for optimal outcomes. This study aimed to assess GDMT adherence at a teaching hospital and compare discharge prescriptions by residents and attending physicians.
Methods
A retrospective cohort study was conducted at Spring Valley Hospital from August 2023 to March 2024. Patients with HFrEF and decompensated heart failure as the primary reason for admission were identified through electronic health records. Adherence to GDMT at discharge was evaluated based on 2022 American Heart Association (AHA) guidelines, focusing on beta-blockers (BB), angiotensin receptor-neprilysin inhibitors (ARNI), mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter 2 inhibitors (SGLT2i). The primary outcome was comparing GDMT adherence between residents and attending physicians. Secondary outcomes included adherence to individual medications, combination regimens, and reasons for non-adherence.
Results
Among 243 patient charts reviewed, 80 met inclusion criteria (33 residents, 47 attendings). Adherence to beta-blockers was significantly higher than to other GDMT medications (p<0.0001). Residents showed slightly higher adherence to BB, MRA, and SGLT2i, though differences were not statistically significant. Double and triple therapies were prescribed more often than quadruple therapy (p=0.002, p=0.01). Residents demonstrated higher adherence to double therapy with BB and MRA (55% vs. 28%, p=0.02).
Conclusion
Adherence to GDMT for HFrEF was comparable between residents and attending physicians. Improving adherence to key medications can further enhance HFrEF management and patient outcomes.
Antagonistic effect of diffusible metabolites produced by Bacillus velezensis OEE1 against Biscogniauxia mediterranea causing the charcoal canker on olive trees
Authors: Cheffi Manel , Mallek Rahma , Gharsallah Houda , Amara Asma Ben , Karoui Eetizez , Gharbi Yaakoub , Ennouri Karim , Krid Samira , Triki Mohamed Ali
Published: January 2025

An increase in olive trees diseases caused by wood-borne fungi like Biscogniauxia mediterranea has been reported to cause serious damages. Due to the importance of this plant in the Mediterranean countries, the search for sustainable measures to control this disease is necessary. The strain OEE1 of Bacillus velezensis was selected to evaluate its potential to control this fungus. The results showed a high antagonistic activity by dual-plate assays reaching 87% and producing microscopic mycelial alterations. The crude diffusible metabolites when incorporated with different amount in PDA medium revealed a total inhibition of B. mediterranea’s radial growth with a concentration of 75%. This concentration is considered fungicidal for this pathogen. The growth inhibition is accompanied with an obstruction of spores’ germination. An evaluation of the antagonistic potential was also assessed on 2-years-old olive trees cv chemlali to treat preventively and curatively the cankers developed after the artificial inoculation with B. mediterranea. This study provides valuable findings to encourage the use of B. velezensis OEE1 as suitable biocontrol agent against charcoal canker disease in olive trees.
Dual-Polarization Quadrupling Generation for RoF-DWDM Transmission Using OCS with Dual-Parallel DD-MZM Under Nonlinear Effects
Authors: chebra abdennour fellag , Bendaoud Mohammed , Imam Abderrahmane , Ghnimi Said , Gharsallah Ali
Published: January 2025

The rapid advancement of next-generation wireless networks is revolutionizingcommunication systems, focusing on providing high-speed connectivity, extensivebandwidth, and broad coverage. Within this framework, Radio over Fiber (RoF)technology has gained prominence as an innovative approach to enable broadbandwireless communication, utilizing micro and pico cells integrated with centralizedaccess networks. This paper presents and evaluates a dual-polarization quadruplingmillimeter-wave (mm-wave) generation technique based on Optical CarrierSuppressed (OCS) modulation to enhance RoF-DWDM system performance. Theproposed technique utilizes dual-polarization dual-parallel modulators integratedwith phase-shifting operations to enable OCS transmission, suppressing unwantedspectral components and facilitating efficient mm-wave generation. The approachgenerates dual-polarization RF signals at 28 GHz, supporting data rates of 10Gbps per polarization state, and achieves high-capacity transmission in a 40-channel system over 150 km of SMF with 75 GHz channel spacing. The impactof nonlinear effects poses significant limitations on the transmission capacitywhen utilizing a filterless OCS approach in each modulator within the system.These effects lead to a degradation in spectral integrity, impairing overall performance.the integration of a 4th-order Bessel filter into the transmission systemeffectively mitigates these issues. This solution suppresses unwanted sidebands, enhances spectral efficiency, and reduces interference, resulting in improved systemperformance and reliability. The performance of the proposed system hasbeen evaluated and optimized to achieve high-quality transmission while minimizingthe impact of nonlinear effects. Simulations reveal the most efficient inputpower levels between 5 dBm and 10 dBm, resulting in a quality factor of 8.16 and a BER of 1.66 x 10−16 using the filterless OCS communication method. Theincorporation of an OBPF improves transmission performance, achieving a qualityfactor of 14.59 and a BER of 1.12 x 10−48 The system demonstrates resilienceto nonlinearities, achieving an FWM efficiency of 42.5 dBm and reducing SRSeffects to 0.2 dBm. PMD analysis indicates a sensitivity range of -36.9 dBm to -9.8 dBm at a PMD coefficient of 0.2 ps/km; however, higher PMD values degradesensitivity. Despite these challenges, the system confirms its suitability for longdistance,high-capacity transmission in next-generation RoF-DWDM networks.
Neutrophil-to-lymphocyte ratio dynamics: prognostic value and potential for surveilling glioblastoma recurrence
Authors: Chung Meng-Wu , Tzeng Ching-Chieh , Huang Yin-Chen , Wei Kuo-Chen , Hsu Peng-Wei , Chuang Chi-Cheng , Lin Ya-Jui , Chen Ko-Ting , Lee Cheng-Chi
Published: January 2025

Purpose
Glioblastoma (GBM) is a challenging malignancy with a poor prognosis. While the neutrophil-to-lymphocyte ratio (NLR) is reported to correlate with the prognosis, the significance of changes in the NLR and its prognostic value in GBM remain unclear. This study aims to evaluate changes in the NLR and its predictive value for GBM prognosis and recurrence.
Methods
The cohort included 69 newly-diagnosed GBM patients undergoing a standard treatment protocol. NLR was assessed at multiple time points. The dynamic change in NLR (dNLR), defined as the NLR at the point of interest (post-CCRT or post-Stupp) divided by the preoperative NLR, also was assessed. Univariate and multivariate COX regression analyses were conducted to assess the association between the NLR, dNLR and overall survival (OS) and progression-free survival (PFS).
Results
Univariate analysis revealed that age at diagnosis ≥ 70 (p = 0.019) and post-Stupp dNLR ≥ 1.3 (p = 0.006) were significantly associated with shorter OS. Significant correlations were found between pre-operative KPS ≥ 60 (p = 0.017), gross total resection (p = 0.042), post-Stupp dNLR ≥ 1.3 (p = 0.043) and PFS. Multivariate analysis showed age at diagnosis ≥ 70, pre-operative KPS ≥ 60, post-Stupp NLR ≥ 5 and dNLR ≥ 1.3 were significantly associated with a shorter OS. Significant correlation was found between pre-operative KPS ≥ 60 and PFS.
Conclusion
This study revealed that post-Stupp NLR ≥ 5 and dNLR ≥ 1.3 correlated significantly with a worse glioblastoma prognosis and dNLR could be a more reliable parameter for surveilling glioblastoma recurrence.
Efficacy and Safety of varying dosage of Gefapixant in Patients with chronic cough. A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Authors: Hudaib Muhammad , Tabassum Nabira , Malik Hurais , Tariq Umer Bin , Klair Nimra , Abedin Mariam Farhan Essa , Zafar Fatima , Abdullah Muhammad , Shahzad Mohammad Saiem , Syed Abdul Rehman Shah , Rabbani Samra , Khatri Mahima , Kumar Satish
Published: January 2025

Background
A cough that remains unresolved for longer than 8 weeks is referred to as chronic cough, and it is estimated that 10% of the adult population of the world suffers from chronic cough. Gefapixant is a purinergic receptor P2x3 receptor antagonist. P2x3 receptors are ATP-gated ion channels on the peripheral sensory C fibers in the airways.
Objective
We conducted a systematic review and meta-analysis of RCTs to investigate whether the chronic cough patients would benefit from gefapixant administration or not when compared to placebo.
Methods
We selected only those double-arm randomized controlled trials (RCTs) which included participants presenting with a chronic cough in patients 18 years or older. We excluded all the articles published in languages other than English Language. Furthermore, all the studies other than RCTs were also omitted. Articles yielded from the electronic search were exported to EndNote Reference Library software to remove any duplicates. Analyses were done using the Review Manager 5.4 tool. Mean values and standard deviations were retrieved for the continuous outcomes given as raw data.
Results
8 RCTs selected for the statistical analysis consisted of 2024 participants (1011 in the intervention group and 1013 in the placebo group). The outcomes resulted to be significant with 24-hour cough frequency, the mean difference [MD] = -5.26, 95% confidence interval [CI] -7.18 to -3.33; p = 0.00001; n = 3518, awake cough frequency (c/h) [MD] = -6.78, 95% confidence interval [CI] -9.46 to -4.09; p = 0.00001; n = 3472 patients., night cough frequency (c/h) [MD] = -4.07, 95% confidence interval [CI] -5.49 to -2.65; p = 0.00001; n = 479, patients cough severity VAS (mm) [MD] = -14.84, 95% confidence interval [-19.92, -9.76], p = 0.00001, n= 1297, cough severity diary difference [MD] = -0.85; 95% confidence interval [CI]: -1.14, -0.56; p-value = 0.00001; n = 1219, Total LCQ score MD=2.04, 95% CI = 1.09 to 2.98, p<0.0001, n =869.
Conclusion
To conclude, the lowest efficacious dose was 50 mg twice daily and helped reduce 24-hour cough frequency, awake cough frequency, night cough frequency, and cough severity using VAS in a dose-dependent manner. Gefapixant showed a significant risk of adverse events which include dysgeusia, hypogeusia, nausea, any adverse event, taste-related and drug-related adverse events, and serious AEs
Enhanced stability and efficacy of a lyophilized mRNA SARS-CoV-2 vaccine incorporating novel Ionizable lipids after one year storage at 25ºC
Authors: Mata Elena , Broset Esther , Matute Carlos , Stoian Andrei Mihai , Adame Susana , Alejo Teresa , López Alexandre , Andrés Beatriz , Heredero Juan , de Miguel Diego , Giménez-Warren Javier , Lampaya Verónica , Casabona Diego , Calvo Alba , Quincoces Gema , Peñuelas Iván , Gamazo Carlos , Uranga-Murillo Iratxe , Peña Natacha , Arias Maykel , Pardo Julian , Moreno Bernardino , Badiola Juan , Martínez Juan , Pérez Esther
Published: January 2025

mRNA vaccines have shown great efficacy against SARS-CoV-2, yet challenges remain in optimizing vaccine components to achieve enhanced immune response and vaccine stability. In this study, we developed CPVax-CoV, a new lyophilized mRNA vaccine that features novel thiolactone-based ionizable lipids and newly designed untranslated regions (UTRs) for enhanced expression. Incorporation of these optimized components into our vaccine candidate CPVax-CoV significantly improved immune responses in mice compared to commercially available mRNA vaccines. Moreover, lyophilized CPVax-CoV has proven to be thermostable, maintaining its biological activity for up to one year at 4°C and 25°C after lyophilization, overcoming the cold-chain limitations of current mRNA vaccines. This vaccine demonstrates protective efficacy against ancestral SARS-CoV-2 and Omicron XBB variant, offering a scalable solution for global distribution and pandemic preparedness. These findings underscore the potential of this platform for future next-generation mRNA vaccine development.
A survival prognostic model for gastro-intestinal lymphomas
Authors: Wu Shaojie , du junru , Ma Jie , Huang Li , Peng Zhiqiang , Ling Yiwen , Deng Xiaofang , Zhu Weijian , Li Hongliang , Wu Ming , Li Di , Guo Jing , Liao Ming , Gale Robert , Wang Hua , Li Yuhua
Published: January 2025

Primary gastro-intestinal lymphomas are the most common extra-nodal lymphomas but there is no widely-accepted survival prognosis model. We interrogated data from 1 023 consecutive newly-diagnosed people with primary gastro-intestinal lymphoma. The most common sites were stomach (55%). Diffuse large B-cell lymphoma (DLBCL) was the most common diagnosis (65%) followed by mucosa associated lymphoma (MALT) (20%). In people with DLBCL, survival of those with stomach or large intestine lymphomas was better compared with those with small intestine lymphomas (P = 0.03) and multiple sites (P < 0.01). People with DLBCL receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) had better survival compared with those receiving CHOP only (P < 0.001). In multi-variable analyses of the training cohort with DLBCL age (P < 0.001), Lugano stage (P = 0.03) and albumin (P = 0.04) and lactic dehydrogenase (LDH) concentrations at diagnosis (P = 0.01) were significantly-associated with 10-year survival. Results were tested in a validation cohort. Using these co-variates we constructed a survival prognosis nomogram model with C-statistics of 0.82 (0.77, 0.86) and 0.80 (0.74, 0.85) in the training and validation cohorts. Our model, if further validated, can be used to predict survival of people with primary gastro-intestinal lymphomas.
Improving Real-time 3D Reconstruction and Semantic Segmentation for AR Applications
Authors: Nong Yu
Published: January 2025

This paper presents an innovative approach to enhancing real-time 3D reconstruction and semantic segmentation for Augmented Reality (AR) applications using advanced Artificial Intelligence (AI) techniques. We introduce a novel hybrid architecture that combines a lightweight NeRF (Neural Radiance Fields) variant with a real-time semantic segmentation network. Our method achieves state-of-the-art performance in both 3D reconstruction accuracy and semantic understanding while maintaining real-time performance on mobile AR devices. Experimental results demonstrate significant improvements in reconstruction quality, segmentation accuracy, and computational efficiency compared to existing methods.
GPT vs Human Legal Texts Annotations: A Comparative Study with Privacy Policies
Authors: Cevallos-Salas David , Estrada-Jiménez José , Guamán Danny S. , Rodríguez David , Álamo José M. del
Published: January 2025

High-quality corpora of annotated privacy policies are scarce, yet essential for training, testing, and evaluating accurate machine learning models. However, elaborating new corpora remains an error-prone and resource-intensive task, heavily reliant on highly specialized and hard-to-find human annotators. Recent advancements in Generative Pre-trained Transformers (GPTs) open the possibility of using them to annotate privacy policies with performance comparable to that of human annotators, thereby streamlining the process while reducing human resource demands. This paper presents a novel method for annotating privacy policies based on a codebook, a well-designed prompt, and the analysis of logarithmic probabilities (logprobs) of a GPT's output tokens during the annotation process. We validated our method using the GPT-4o model and the well-known, open, multi-class, and multi-label OPP-115 corpus, achieving performance comparable to 80% of human annotators in segment-level annotation and matching 90% of human annotators in a full-text level annotation. Furthermore, incorporating logprobs analysis allowed the method to match the performance of all human annotators in full-text level annotation, suggesting that context enhances the task. These findings demonstrate the potential of our method to automate annotations with performance similar to human annotators while significantly reducing resource demands.
CASH WAQF LINKED SUKUK (CWLS) DALAM PESPEKTIF MASLAHAH MURSALAH
Authors: Winarto Ashif Jauhar , Rifai Achmad , Ghozali Muhammad Lathoif
Published: January 2025

Cash Waqf Linked Sukuk (CWLS) was born because of the demands of modern times that require everything to be easy, practical and simple. However, behind all the conveniences provided by cash waqf, there is still a fundamental problem, namely the issue of legal legality. The legal status of cash waqf is viewed from the perspective of maslahah mursalah. This research belongs to the category of literature research, while in analyzing the data obtained, the researcher uses a prescriptive analysis approach. The data collection technique used is documentation technique. Cash waqf has been considered valid, because the conditions for maslahah haqiqi (maslahah that are actually realized in real terms in the field), maslahah ammah (maslahah that are general in nature are not only enjoyed by a certain person or group of people), maslahah mulaman bi syar'i (maslahah that is in harmony with and T does not conflict with the Shari'ah) has been fulfilled in cash waqf. So that the legal status of cash waqf is halal. Moreover, the requirements of al habsu ma‟a baqo aynihi (holding goods without losing their essence) also remain in cash waqf.
NEGOSIASI DALAM HUKUM ISLAM:
Authors: Fauziah Umi Fajar , MUSONNIF AHMAD
Published: January 2025

Fitrah Zakat plays a central role as an obligatory duty that cannot be ignored. Fitrah zakat is a mandatory contribution for every individual in the Muslim community, known as (zakat al-nafs). It must be distributed accurately to those entitled (mustahiq), ensuring the goal of meeting the needs of the mustahiq during festive occasions is achieved. This research is motivated by the zakat distribution practices in Pojok Village, where several hamlets distribute zakat evenly among the local community. The study critically examines the concept of negotiating zakat distribution within Islamic law, particularly through the principle of "harmony." The research employs qualitative and field research methods, gathering data through direct field observations and deductive analysis. Primary data sources include interview results, supplemented by secondary data from relevant literature. Data collection techniques involve observation, interviews, and documentation. Data analysis techniques include data verification and presentation, with data validity ensured through triangulation and extended research.
THE INFLUENCE OF SCHOOL PRINCIPALS LEADERSHIP, COMPETENCY AND COMMITMENT ON THE PERFORMANCE OF YADIKA HIGH SCHOOL TEACHERS IN WEST JAVA
Authors:   Postgraduate Program of Satya Negara Indonesia University., Ashri Akbariani Dinny , Siregar Edi ,   Postgraduate Program of Satya Negara Indonesia University.
Published: January 2025

This research aims to provide an overview of school principal leadership, teacher competency and commitment to the performance of Yadika High School teachers throughout West Java. This quantitative research with a causality model analyzes the influence of the independent variable on the dependent variable through primary data and secondary data. The population in this study was Yadika High School teacher in West Java, totaling 256 teachers and the sample used was permanent foundation teachers, totaling 42 people. Leadership, competence and commitment are the independent variables while teacher performance is the dependent variable. The results of the research show that leadership, competence and commitment simultaneously influence teacher performance by 59%, while 41% are influenced by other factors not examined in this research. Leadership variables partially influence teacher performance. The competency variable partially influences teacher performance. The commitment variable partially influences teacher performance.
CASE OF NAXD DEFICIENCY PRESENTING WITH DEVELOPMENTAL REGRESSION AND PROGRESSIVE ENCEPHALOPATHY
Authors:   Pediatric Neurology, Armed Forces Hospital Southern Region, Saudi Arabia., Alamer Hajer , Al Sumaili Mohammad ,   Consultant Pediatric Neurologist &Epileptologist Armed Forces Hospital, Southern Region, Saudi Arabia., Saeed Muhammad ,   Consultant Pediatric Neurologist, Armed Forces Hospital, Saudi Arabia.
Published: January 2025

Introduction: Developmental regression in children can indicate underlying neurodegenerative or metabolic diseases, often posing diagnostic and therapeutic challenges. Defects in NAD(P)HX dehydratase (NAXD), an enzyme crucial for maintaining cellular NAD(P)H levels, are implicated in progressive encephalopathy. This case report highlights NAXD deficiency as a rare but critical cause of developmental regression, with a focus on genetic findings and clinical presentation.

Case Presentation: A 9-month-old infant with a history of normal development until 7 months of age presented with rapid developmental regression, including loss of motor skills, social engagement, and speech. Clinical examination revealed hypotonia, hypertonia, exaggerated reflexes, hepatomegaly, and pancytopenia. Genetic testing identified a homozygous mutation in the NAXD gene, confirming the diagnosis. MRI showed brain atrophy and restricted diffusion in the basal ganglia, while MRS indicated metabolic abnormalities. Despite supportive therapy, the child developed seizures, respiratory failure, and multiorgan dysfunction, eventually leading to death.

Discussion: NAXD deficiency leads to toxic accumulation of NAD(P)HX metabolites, impairing mitochondrial function and causing progressive neurological decline. Our case presents atypical features, including the absence of fever-triggered neurological deterioration, which suggests subtle or unnoticed febrile episodes may contribute to symptom exacerbation. The use of whole-exome sequencing (WES) was crucial for diagnosis, aligning with other reports linking NAXD mutations to early-onset encephalopathy and seizures.

Conclusion and Future Directions: This case underscores the importance of early genetic testing in diagnosing rare metabolic disorders like NAXD deficiency. Future research should focus on therapeutic strategies to restore NAD(P)HX balance, including mitochondrial-targeted therapies, and the identification of biomarkers for disease progression. Further studies are needed to optimize clinical management and improve outcomes in affected individuals.
ZP3 Expression in Pancreatic Adenocarcinoma: Its Implications for the
Prognosis and Therapy
Authors: Lyu Guizhen , Li Dongbing
Published: January 2025

Background:

The role of Zona pellucida glycoprotein 3 (ZP3) is unclear in pancreatic
adenocarcinoma (PAAD).

Objective:

This study aimed to explore the role of ZP3 in PAAD.

Methods:

A comparative analysis of ZP3 gene expression was performed to discern differences between
various types of cancer and PAAD, leveraging data sourced from The Cancer Genome Atlas
(TCGA). This study aimed to assess the role of ZP3 as a potential diagnostic marker for
PAAD. The relationship between ZP3 levels and clinical characteristics, as well as patient outcomes,
was scrutinized. Additionally, genomic enrichment analysis was carried out to uncover the
underlying regulatory mechanisms associated with ZP3. The study further delved into the association
of ZP3 with immune system interactions, checkpoint gene expression, Tumor Mutational Burden
(TMB), microsatellite instability (MSI), and tumor stemness index (mRNAsi). The aberrant
expression patterns of ZP3 in PAAD cell cultures were confirmed through the application of quantitative
reverse transcription PCR (qRT-PCR) techniques.

Results:

ZP3 exhibited aberrant expression in both pan-cancer and PAAD. A significant correlation
was observed between increased levels of ZP3 expression in PAAD patients and histologic
grade (p = 0.026). Elevated ZP3 expression in PAAD was found to be significantly associated
with poorer overall survival (p = 0.003), progression-free survival (p = 0.012), and disease-specific
survival (p = 0.002). In PAAD, the level of ZP3 gene expression was statistically significant (p
< 0.001) and recognized as a key determinant of patient prognosis. ZP3 exhibited associations
with various biological pathways, including primary immunodeficiency, oxidative phosphorylation,
and other pathways. ZP3 expression demonstrated correlations with immune infiltration, immune
checkpoint genes, TMB, MSI, and mRNAsi in PAAD. Moreover, a pronounced negative
correlation was detected between ZP3 expression levels and the therapeutic effectiveness of various
medications, including selumetinib, bleomycin, FH535, docetaxel, and tanespimycin, within
the context of PAAD. Elevated levels of ZP3 were consistently observed in cell line models of
PAAD.

Conclusion:

ZP3 has the potential to serve as a prognostic biomarker and therapeutic target for patients
with PAAD.
Implications of EBV-Encoded and EBV-Related miRNAs in Tumors
Authors: Awasthi Prankur , Kohli Arjun Singh , Dwivedi Manish , Hasan Saba
Published: January 2025

Over 90% of people are infected with the human g-herpesvirus known as the Epstein-
Barr virus (EBV). Cancers, such as gastric carcinoma, non-Hodgkin’s lymphoma, nasopharyngeal
carcinoma, Hodgkin’s lymphoma, and Burkitt lymphoma, are thought to be linked with EBV. It is
noteworthy that the first virus discovered that encodes microRNAs (miRNAs) was EBV, and these
miRNAs show expression at the different phases of EBV infection. There is growing evidence that
EBV-encoded miRNAs influence the growth of EBV-associated tumors. These EBV miRNAs, i.e.,
BamHI-H rightward fragment 1-derived microRNAs (BHRF1miRNA) and BamHI-A rightward
fragment-derived microRNAs (BART miRNAs), are crucial for the persistence of viral infection
and the avoidance of host defenses. Currently, significant advancements have been made in
analyzing the microRNAs that are found in the duration of EBV infection, in vitro studies identified
molecular targets of miRNAs and in vivo studies enhanced our understanding regarding the
pathophysiology of these molecules. An extensive look into the pro-carcinogenic impact of
microRNAs associated with EBV will increase our understanding of the molecular mechanisms of
EBV-associated tumors. In this paper, we have highlighted the functions of miRNAs in EBV
infection as well as recent developments in miRNA-based therapeutic and diagnostic approaches
that could be useful for EBV-related malignancies. Significantly, targeted therapies against EBV
miRNAs are advancing rapidly, with emerging approaches such as miRNA sponges, anti-miRNA
oligonucleotides, and CRISPR/Cas9 technologies. These innovations indicate the imminent onset of
a new era in the treatment of EBV-associated tumors.
Ginsenoside Compound C Targets Prediction for Intervertebral Disc Degeneration Treatment
Authors: Zhang Yizhi , Wei Ziyan , Wang Dongxin , Chen Shijie , Yang Fengguang , Jia Jingwen , Qiu Xiaoming , Kang Xuewen
Published: January 2025

Background:

Intervertebral Disc Degeneration (IDD) is a major cause of lower back pain.
Ginsenoside compound C (GCC) has shown potential in treating IDD, but its specific targets and
mechanisms remain unclear.

Objective:

This study aimed to investigate the potential molecular mechanisms of GCC in the treatment
of IDD using network pharmacology and molecular docking approaches.

Method:

Public databases were utilized to identify 100 targets related to GCC and 20,757 targets
associated with IDD, of which 96 common targets were determined through cross-analysis. A Protein-
Protein Interaction (PPI) network was constructed using the STRING database, and key gene
clusters were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes
(KEGG) analyses were performed to explore the biological processes and pathways involved. Molecular
docking was conducted to verify the binding of GCC to key proteins.

Results:

Six key genes, including HSP90AA1, CASP3, MAPK1, EGFR, HIF1A, and PIK3CA, were
identified as central to the PPI network. GO analysis suggested that GCC's targets are involved in
intracellular processes, while KEGG analysis highlighted the IL-17 and TNF signaling pathways.
Molecular docking confirmed stable binding between GCC and key proteins, with binding energies
ranging from -3.58 to -2.01 Kcal/mol.

Conclusion:

GCC may inhibit the IL-17 and TNF signaling pathways by interacting with key proteins,
potentially contributing to the treatment of IDD.
Beyond the Surface: Tracing the Evolution of Inflammatory Mechanism in Depression through Bibliometric Analysis
Authors: Xu Zhang-Yang , Zhang Ting , Gong Hong , Zheng Hong , Liu Mei-Shan , Guo Bing-Hang , Wang Yun-Xia , Su Wen-Jun
Published: January 2025

Background:

Depression is a common mental illness that has become a major economic
burden worldwide. Recently, increasing evidence has highlighted the inflammatory mechanism
of depression. In order to understand the research status of this field, this study used the bibliometric
analysis method to overview the research content and progress, as well as analyze the development
trend and limitations.

Methods:

In this study, articles and reviews were included in the specific search strategy. The
matched papers were exported from the Web of Science database. CiteSpace 6.3 R1 and Bibliometrix
(R package) were utilized to generate bibliometric and knowledge maps.

Results:

A total of 25,063 articles were included in this study. The number of publications in this
field has gradually increased, especially in recent years. These papers come from 156 countries,
led by the United States and China mainland. The leading research institution is the University of
Toronto (Canada). Brain Behavior and Immunity is the journal with the most publications and the
most frequently co-cited journals. Among 91,100 authors, Maes M has the most publications and
co-citations. According to the keywords burst and co-cited reference analysis, the hotspots in the
field in recent years include kynurenine, c-reactive protein, neuroinflammation, and gut microbiota.

Conclusion:

Although abundant academic achievements have been made on the inflammatory
mechanism of depression, there is still a long way to go before these research results can be applied
to clinical practice. Strengthening international academic exchanges and cooperation may
promote breakthroughs in this field.
Protective Effects of Hydrogen Treatment Against High Glucose-Induced Oxidative Stress and Apoptosis via Inhibition of the AGEs/RAGE/NF-κB Signaling Pathway in Skin Cells
Authors: Yu Pan , Hong Nan , Wu Qiong , Zhao Zhipeng
Published: January 2025

Background:

Diabetic wounds are major clinical challenges, often complicated by
oxidative stress and free radical generation. Hydrogen (H2), a selective antioxidant, offers potential
as a therapeutic agent for chronic diabetic wounds. However, its precise mechanisms remain
underexplored.

Objective:

This study aimed to investigate the protective effects of H2 on high glucose-induced
oxidative damage and apoptosis in human skin cells.

Methods:

HaCaT keratinocytes and HSF fibroblasts were treated with high glucose or AGEs. Cell
viability, oxidative stress markers, inflammatory cytokines, and apoptosis were analyzed.
AGEs/RAGE/NF-κB signaling was evaluated via Western blot.

Results:

H2 treatment significantly reduced ROS, MDA, IL-1β, and TNF-α levels, while enhancing
SOD and GSH activity. It also inhibited AGEs/RAGE/NF-κB signaling and apoptosis.

Conclusion:

Hydrogen therapy protects against oxidative stress and inflammation induced by
high glucose or AGEs, offering potential as an adjunctive treatment for diabetic wound healing.
Evaluation of Salivary and Serum micro RNA 146a, 200c and its Target Gene PTEN in Chronic Periodontitis Patients and their Response to Non-Surgical Periodontal Therapy
Authors: Prasanna Jammula Surya , Apoorva Kunnel
Published: January 2025

Background:

Periodontitis destroys the tooth's supporting structures and attachment apparatus. Local or systemic factors can cause it. Traditionally, diagnosis is based on clinical parameters that may not consistently reflect an accurate confirmation. Biochemical and genetic analyses can provide deeper insights. MicroRNAs (miRNAs) regulate the immune and inflam-matory response to microbial pathogens. Detecting and evaluating miRNAs can be an important diagnostic parameter. This study aimed to assess the expression of miRNA 146a,200c, and its target gene PTEN to non-surgical periodontal therapy in serum and saliva.

Materials and Methods:

This interventional comparative study was conducted on 120 patients of both genders, ages between 35 and 55. Non-surgical periodontal therapy (NSPT) scaling and root planing were performed on all subjects, and their saliva and serum samples were collected before and after 8 weeks of NSPT. Quantitative rt-PCR (reverse transcriptase Polymerase Chain Reaction) analysis was conducted on all samples. The statistical analysis was done using SPSS version 22, and comparisons were made using paired t-tests, independent t-tests, and Pearson’s correlation coefficient. The statistical significance level was set at a ‘P’ value of less than 0.05.

Results:

It has been observed that there was a significant difference of miRNA in both serum and saliva samples 146a,200c, and the PTEN gene expression, from the beginning to 8 weeks. Sig-nificant variation was not observed when comparing the levels between serum and saliva.

Conclusion:

miRNA 146A, 200c, and PTEN genes are interrelated with periodontitis. We can consider them as future biomarkers of periodontal diseases.
Vitamin B12 Malabsorption: The Pathophysiological Impacts on Neurological and Hair Physiology
Authors: Rathore Prince Nikhil , Gupta Sakshi , Madhariya Rashmi , Ram Alpana
Published: January 2025

Vitamin B12 (cobalamin) is a water-soluble vitamin. It is a crucial vitamin for the health
of humans, contributing immensely to numerous biological processes. This study aims to highlight
the importance of vitamin B12 in nourishing hair growth and the nervous system and how its malabsorption
might trigger various problems in the body. Major absorption of vitamin B12 takes place
in the small intestine from several foods like milk, eggs, fish, liver, meat, and yoghurt. Several factors
can cause malabsorption of vitamin B12, including atrophy of the gastric mucosa, disease of the
terminal ileum in the body, and cigarette smoking. These factors can lead to the demyelination of
large nerve fibers in the spinal cord, a variation in the fraction of S-adenosylmethionine to S-adenosylhomocysteine,
and an alteration in TNF and epidermal growth factor (EGF) levels, which can
cause optic neuropathy and hair loss. Maintaining a proper diet and leading a healthy lifestyle are
crucial for maintaining vitamin B12 levels in the body, as the body can store this vitamin for up to
3–6 years. Mainly, the level of vitamin B12 in the healthy human body is 160 to 950 picogrammes
per millilitre In conclusion, the factors leading to malabsorption of vitamin B12 and their consequent
deficiencies were examined. The body's numerous crucial functional pathways are influenced by
vitamin B12.
Biochar Amendment Alleviates the Risk of High-Salinity Saltwater Intrusion for the Growth and Yield of Rice (Oryza sativa L.)
Authors: Faiyue Bualuang
Published: January 2025

Introduction:

Saltwater intrusion poses a serious risk to global food security. As a soil amendment, biochar mitigates the negative effects of saltwater intrusion in rice, yet the beneficial effects on agricultural productivity with different exposure times and salt concentrations have not been fully examined.

Methods:

A pot experiment was conducted to investigate the effects of 30% (w/w) rice husk biochar on the growth, ion accumulation, and yield of the Phitsanulok 2 rice cultivar under salt stress due to saltwater intrusion. Rice plants were grown in saline soil amended with biochar and were salinized with 6, 8, and 10 dS/m saltwater for 1, 2, and 3 months. A treatment without biochar was taken as the control.

Results:

The results showed that biochar amendment significantly increased the survival, shoot height, and tiller numbers of rice treated with the 6-10 dS/m saltwater for 1 and 2 months, as well as the treatment with 6 dS/m salt water for 3 months, in comparison with the control. The grain yield was about 40 g/pot for rice with biochar treated for 1 month with 6-10 dS/m saltwater and for the rice treated for 2 months with 6 dS/m.
The results indicated that biochar application could alleviate the intrusion of high-salinity water for 1 month of salt exposure, and it could alleviate the intrusion of medium-salinity water for 2 months.

Conclusion:

Therefore, a 30% (w/w) rice husk biochar amendment is a reliable strategy for mitigating the risks of saltwater intrusion for the growth and productivity of rice.
Molecular Mechanisms Underlying Metabolic Syndrome
Authors: Marwa Mohamed Hosny  , Nora Hosny  , Ahmed Saber Shams
Published: January 2025

Metabolic syndrome (MetS) has become a worldwide health problem,
affecting children and adults globally. The prevalence of MetS is rising all over the
world due to increasing obesity and sedentary lifestyles. MetS is caused by the
interaction of both genetic and environmental factors.MetS is characterized by complicated, multidimensional, and sophisticated molecular
pathways that involve insulin resistance, inflammatory processes, and hereditary
predispositions.
Here we are trying to focus on common molecular mechanisms that underlie MetS
occurrence, aiming to offer a better understanding of their role in MetS and helping in
developing prognostic/diagnostic tools and targeting novel therapeutic options.
The Interplay between Metabolic Syndrome and Behavior
Authors: Shimaa Mohammad Yousof  , Asmaa Seddek
Published: January 2025

Metabolic syndrome (MetS) indicates a cluster of symptoms that include
abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. Even though the
etiology of MetS is unknown, it is thought to be multifaceted, with a complicated
interaction between genetic predisposition and significant changes in lifestyle behavior,
such as physical inactivity, high carbohydrate diets, and alcohol and cigarette use. The
circadian system regulates many physiological and behavioral rhythms, which operate
on 24-hour cycles. Circadian rhythm disturbances are also seen in various clinical
disorders linked to adipose tissue functioning. In addition, night-shift employees who
have their rest-activity cycles reversed are more likely to acquire MetS. Individuals
with MetS experienced more seasonal variations in mood and behavior, with obesity
being a substantial risk factor for metabolic syndrome. MetS has been linked to
psychiatric illnesses. In those diagnosed with major depressive disorder and bipolar
disorder in adulthood, disruption to biological rhythms (sleep, social activities, and
eating habits) has been linked to essential components of MetS. MetS and its
components were found to be connected to a higher risk of suicide. It is apparent that
the relationship between behavior and MetS is bidirectional, and each component can
affect the other. Awareness of MetS-related factors can aid in identifying high-risk
individuals and implementing disease prevention and control strategies, as well as
lifestyle adjustments. Lifestyle modification can help to improve the MetS condition
and behavior.
Multitarget Pharmacotherapeutic Strategies for Metabolic Syndrome and Related Disorders: Perspectives on Personalized Medicine Using a Pharmacology Network Approach
Authors: Samah M. Elaidy  , Fatma S. Samman  , Samar Imbaby
Published: January 2025

One of the most common metabolic illnesses worldwide is the MetS. In the
MetS and its related disorders, rationalized and evidence-based pharmacotherapeutic
strategies are corner stones in the mitigation of polypharmacy. The pharmacology
network approach and enhanced bioinformatics tools related to the epigenetic,
genomic, transcriptomics, proteomic, and metabolomic levels are considered useful
bench-side tools for the exploration of molecular preventive and therapeutic
multitargets. Molecular multitarget therapy is regarded as a novel pharmacological
strategy that forms the foundation of personalized and precision medicine. That will
decrease the socioeconomic burden and will improve the health-related quality of life.
The Role of Bariatric and Metabolic Surgery in the Management of Metabolic Syndrome
Authors: Halit Eren Taşkın  , Hafize Uzun
Published: January 2025

Metabolic syndrome (MetS) is characterized by central obesity, glucose
intolerance, dyslipidemia, and hypertension. This is attributed to an increased
inflammatory state resulting from increased cytokine synthesis from adipose tissue.
Almost all of the medical problems associated with metabolic syndrome can be more
successfully remised in the long term by bariatric-metabolic surgery (BMS) compared
to conservative methods. In past years, the benefits of BMS have been attributed to
weight loss; however, currently, it has been well described that anti-inflammatory
response and remission of T2DM and other comorbidities begin in the first weeks after
procedures. Moreover, there is also sufficient evidence that BMS helps in the remission
of integral components of MetS, such as hyperlipidemia, hypertension, and
cardiovascular diseases, in the long term where many patients do not even require
medical treatment. The International Diabetes Federation (IDF) and recent guidelines
recommend that metabolic surgery may be considered if glycemic control is not
achieved despite optimal treatment if the patient's body mass index (BMI) is 30kg/m2
and above.