bluuebunny/crossref_metadata_2025_split huggingface dataset:
New acorane-sesequiterpenes and anti-retinoblastoma constituents from the marine algicolous fungus Trichoderma harzianum NTU2180 guided by molecular networking strategy
Authors: Gu Andrea , Lin Fan-Li , Lu Chung-Kuang , Yeh Tz-Wei , Chen Yih-Fung , Wu Ho-Cheng , Lee Tzong-Huei 
Published: January 2025

Abstract

Background

Trichoderma species, known as biocontrol agents against plant diseases, contain diverse compounds, especially terpenoids, with various bioactivities. To facilitate the exploration of bioactive secondary metabolites of Trichoderma harzianum NTU2180, the OSMAC approach MS/MS molecular networking was applied in the current study.

Results
The feature-based molecular networking (FBMN) analysis showed that T. harzianum NTU2180 fermented on germinated brown rice (GBR) produced more terpenoids. Here, two new acorane-sesequiterpenes, trichospirols A (1) and B (2), and 12 known compounds (3 − 14) were isolated from the EtOAc layer of T. harzianum NTU2180 fermentation on GBR. Structures of these compounds were determined through NMR, UV, IR, and MS analyses. The absolute configuration of trichospirols A (1) was also elucidated by x-ray with Cu K-α radiation. Among them, six compounds (1, 2, 3, 4, 5, and 11) were annotated as terpenoids by the NPClassifier on FBMN. 5-Hydroxy-3-hydroxmethyl-2-methyl-7-methoxychromone (7) and ergosterol peroxide (11) showed significant anti-angiogenic activity in ex vivo experiments with respective 0.57 ± 0.12- and 0.20 ± 0.12-fold changes. In addition, compound 11 displayed cytotoxicity against Y79 retinoblastoma cells with IC50 value of 35.3 ± 6.9 µM.

Conclusions
The current study utilizes FBMN concept with OSMAC approach to accelerate the exploration of potential metabolites of the fungus Trichoderma harzianum NTU2180. Through a series of FBMN-guided isolation and purification, two new acorane-sesequiterpenes and 12 known compounds were obtained. The ex vivo and in vitro experiments were evaluated to assess anticancer isolates. It is worth noting that compound 11 was identified as a dual inhibitor targeting both angiogenesis and proliferation of retinoblastomas. Altogether, the results revealed the novel potential of T. harzianum for developing natural therapeutics against retinoblastomas.
Understanding price momentum, market fluctuations, and crashes: insights from the extended Samuelson model
Authors: Han Qingyuan 
Published: January 2025

Abstract
Although momentum strategies result in abnormal profitability, thereby challenging the efficient market hypothesis (EMH), concerns persist regarding their reliability due to their significant volatility and susceptibility to substantial losses. In this study, we investigate the limitations of these strategies and propose a solution. Our literature review reveals that the volatile profits are due to statistical analyses that assume the persistence of past patterns, leading to unreliable results in out-of-sample scenarios when underlying mechanisms evolve. Statistical analysis, the predominant method in financial economics, often proves inadequate in explaining market fluctuations and predicting crashes. To overcome these limitations, a paradigm shift towards dynamic approaches is essential. Drawing inspiration from three groundbreaking economists, we introduce the extended Samuelson model (ESM), a dynamic model that connects price changes to market participant actions. This paradigm transition uncovers several significant findings. First, timely signals indicate momentum initiations, cessations, and reversals, validated using S&P 500 data from 1999 to 2023. Second, ESM predicts the 1987 Black Monday crash weeks in advance, offering a new perspective on its underlying cause. Third, we classify sequential stock price data into eight distinct market states, including their thresholds for transitions, laying the groundwork for market trend predictions and risk assessments. Fourth, the ESM is shown to be a compelling alternative to EMH, offering potent explanatory and predictive power based on a single, realistic assumption. Our findings suggest that ESM has the potential to provide policymakers with proactive tools, enabling financial institutions to enhance their risk assessment and management strategies.
Sero-molecular prevalence of toxoplasmosis in hemodialysis and peritoneal dialysis patients in Markazi Province, Iran
Authors: Sarmadian Hossein , Shojapour Mana , chegeni Fereshteh , Tabatabaiefar Mohammad Amin , Haghverdi Farshid , Sarmadian Roham , Ghasemikhah Reza 
Published: January 2025

Abstract

Background
Infectious diseases, particularly parasitic infections such as toxoplasmosis, contribute significantly to the morbidity and mortality of hemodialysis patients. Toxoplasma gondii infection poses serious risks, especially to immunocompromised individuals. This study aimed to assess the prevalence of latent toxoplasmosis in dialysis patients in Markazi Province, Iran.

Methods
A total of 181 patients (168 hemodialysis and 13 peritoneal dialysis) were included in this cross-sectional study. Blood samples were collected and tested for anti-Toxoplasma IgG and IgM antibodies using ELISA, while PCR was used to detect T. gondii DNA. Data were analyzed using SPSS, with P < 0.05 considered significant.

Results
Out of 181 patients, 123 (67.95%) were seropositive for IgG antibodies, with the highest prevalence in those aged over 60 years. No cases tested positive for IgM antibodies or T. gondii DNA. Age was significantly associated with higher seroprevalence (P < 0.05), but there were no significant differences regarding gender, dialysis type, or duration of dialysis.

Conclusion
The high prevalence of latent toxoplasmosis in dialysis patients underscores the need for regular screening to prevent serious complications. Given the limitations of serological tests, molecular diagnostics like PCR should be considered for better detection in immunocompromised patients.
Computer-guided identification of novel inhibitors of apoptosis-signaling kinase 1 from Spondia mombim bioactive compounds against colorectal cancer
Authors: Elekofehinti Olusola Olalekan , Popoola Hannah Oluwaseun , Oluwatuyi Adedotun Olayemi , Iwaloye Opeyemi , Akinjiyan Moses Orimoloye , Cecilia Oluwamodupe , Ogundolie Frank Abimbola , Olatunde Olalekan Isaac , Abchir Oussama , Chtita Samir , Rocha Joao Batista Texeira 
Published: January 2025

Abstract

Background
Apoptosis-signaling kinase 1 is a MAPKKK (mitogen-activated protein kinase) overexpressed in various types of human cancer including colorectal cancer. It mediates inflammation and apoptosis and promotes cell proliferation through the transcription of cyclin D1. 5-Fluorouracil remains one of the primary recommended drugs to manage colorectal cancer. However, this drug often causes various adverse effects, notably diarrhea, vomiting, nausea, and leukopenia. Therefore, a novel treatment is required to eradicate these problems. The clinical implication of apoptosis-signaling kinase 1 in the pathogenicity of colorectal cancer makes it an important drug target in the treatment of colorectal cancer. The use of natural compounds in human cancer treatment continues to gain significant attention in the scientific community due to their therapeutic efficacy.

Method
In this study, computational models such as flexible docking, induced fit docking, and binding free energy calculation were employed to identify small molecule inhibitors from known bioactive compounds of Spondias mombin in reference to 5-fluorouracil (Colorectal cancer standard drug) targeting apoptosis-signaling kinase 1.

Results
Molecular docking studies identified 10 promising candidates which include uvaretin, rutin, isoquercitrin, ellagic acid, quercetin, linalool, acetyl eugenol, tangeretin (-)-catechin, and d-sorbitol based on their favorable binding affinity, with uvaretin having the best score (− 11.328 kcal/mol). The results were further validated with more dependable analysis such as induced fit docking and binding free energy calculation. These compounds showed modest indices for ADMET parameters. Molecular dynamic simulation validated ellagic acid and (-)-catechin with greater binding stability as leading compounds.

Conclusion
These compounds showed improved flexible docking results and formed considerable stable interaction with the protein than 5-fluorouracil. They are non-carcinogenic. The oral bioavailability and toxicities of these compounds are promising as compounds obeyed the Lipinski rule of five. The constructed quantitative structure–activity relationship model with a trustworthy R
2 coefficient value supports the inhibition prowess of these compounds. The findings from this research confer that these compounds could be considered potent apoptosis-signaling kinase 1 inhibitors, and these could be confirmed experimentally as lead compounds of apoptosis-signaling kinase 1 inhibitors in colorectal cancer.
Microcephalic osteodysplastic primordial dwarfism type II in four Indian children with PCNT variants
Authors: Singh Amit , Garg Mahak , Shariq Mohammed , Khetarpal Preeti , Panigrahi Inusha 
Published: January 2025

Abstract

Background
Microcephalic Osteodysplastic Primordial Dwarfism Type II (MOPD II) is an autosomal recessive rare genetic condition marked by characteristic clinical symptoms of prenatal and post-natal growth retardation, reduced height, and microcephaly caused by variations in PCNT gene located on chromosome 21q22.

Case presentation
Four patients of Indian origin with growth deficiency and additional clinical features of MOPDII were recruited from a tertiary health care center and whole exome sequencing was performed on blood samples from these patients. Data were analyzed using standard bioinformatic algorithms and possible causal variants identified. Out of 4, 2 patients were identified to have splice site variants, one had nonsense variant, and one with single nucleotide deletion leading to frameshift in PCNT. All identified variants were in homozygous state. The variant PCNT:c.3465-1G > A has previously been reported in two unrelated patients in Israeli Druze population. The c.9273 + 1G > A variant has been documented in two independent studies, one from the United states and the other from the United Kingdom. Two mutations, a nonsense c.5299C > T and a frameshift single nucleotide deletion c.4180delG are currently mentioned in few databases only.

Conclusion
All four patients had significant microcephaly and growth retardation and the new variants were found to be likely pathogenic by in silico analysis. Early detection of the syndrome is essential for early interventions, proper genetic counseling and prenatal diagnosis.
Growing demand for housing and the productivity challenges in developing housing projects in Iraq
Authors: Hassoon Ali , Ghazali Farid Ezanee Mohamed , Khaleel Tareq , Hadi Ahmed 
Published: January 2025

Abstract
The housing sector in Iraq is facing growing demand. However, productivity challenges continue to hinder the timely and efficient delivery of residential projects. Recognising the urgent need to increase construction productivity (CP) in this sector, this study investigates critical factors that impact the performance of horizontal housing projects in Iraq. The novelty of this research lies in its focus on housing skeleton tasks, such as foundations, brickwork, and slabs, which are pivotal to project efficiency. A structured questionnaire was developed, encompassing 47 factors distributed across the planning, design, and construction phases. The survey was administered to a range of industry stakeholders, including project managers, consultants, engineers, and supervisors, and it achieved a high response rate of 79.6%. The results were analysed via a modified weighted relative importance index (RII), which incorporates respondents’ experience levels to yield a nuanced understanding of each factor’s impact. The key findings reveal that planning (RII = 0.874), team size (RII = 0.856), quantity of brickwork (RII = 0.838), supervision (RII = 0.815), and unit area (RII = 0.793) are among the most influential factors on CP. These insights provide valuable guidance for researchers and practitioners in identifying areas for strategic improvement, ultimately supporting the capacity of Iraq’s housing sector to meet escalating demands.
Consensus evidence-based clinical practice guide for the diagnosis and management of osteoporosis in childhood and adolescence
Authors: El Miedany Yasser , Lotfy Hala , Gaafary Maha El , Gadallah Naglaa , Mehanna Annie Nasr , Mahran Safaa , Hassan Waleed , Abu-Zaid Mohammed Hassan , Tabra Samar Abdelhamed , Mortada Mohamed , Radwan Ahmed R. , Mikkawy Dalia El , Maher S. Esam , Eldrainy Ghada , Abdulhady Hala , Mahgoub Marwa , Amer Youmna , Elwakil Walaa 
Published: January 2025

Abstract

Background
The incidence of osteoporosis in children has increased dramatically during the last decade. This has been attributed to better survival rates of children living with chronic disorders, the increased use of medications known to have a negative impact on the children’s bones, and the increased preference for indoor activities and sedentary life in healthy children. Recent advances in pediatric osteoporosis definition, along with a lack of management recommendations or national consensus on its diagnosis and treatment, have led to a wide range of approaches being implemented to manage this illness. The aim of this work was to develop an optimal evidence-based consensus, target-oriented, on-steered therapeutic approach for children with osteoporosis. Based on 15 key clinical questions, a qualitative literature evaluation was conducted to provide evidence-based recommendations for the treatment of pediatric osteoporosis. An expert panel of 14 pediatric osteoporosis specialists conducted a Delphi survey. The level of evidence for each element was assessed using the Oxford Centre for Evidence-based Medicine (CEBM) System, when available, and/or based on the expert panel’s personal experience. All recommendations with an agreement rate of 75% or higher were included.

Results
Thirty-six recommendations, categorized into 13 domains, had evidence 4 or 5 and consequently were included in the Delphi survey. This was assessed online and a response rate of 82.4% was achieved. Delphi 2 round revealed that all the recommendations achieved 75% or more level of agreement and therefore have been accepted and included in this management recommendations. Based on that an algorithm showing an approach to pediatric osteoporosis management and maintenance of therapy has been developed.

Conclusion
For the management of children with osteoporosis, consulting a pediatric bone specialist is strongly advised, either by referral or by advice. This is extremely relevant because children are uniquely capable of recovering spontaneously or with the assistance of medication. This includes also vertebral fractures reshaping. Consequently, there is a huge opportunity to improve bone mass accretion and thus musculoskeletal health in children with osteoporosis.
Risk Stratification Using Tree-Based Models for Recurrence-Free Survival in Breast Cancer
Authors: Oh Eun Jeong , Alfano Catherine M. , Esteva Francisco J. , Baron Paul L. , Xiong Wenxuan , Tortorella Brooke E. , Chen Ellen I. , Chiuzan Cody 
Published: January 2025

PURPOSE
An accurate risk model is critical for risk-stratified cancer care and delivery. We developed a survival decision tree (SDT) model as a risk stratification tool to categorize patients into distinct groups and compared the model performance with other methods through a benchmarking design.

METHODS
Data were obtained from the Northwell Health cancer registry for patients with breast cancer who were initially diagnosed and first seen at one of the nine Northwell facilities between 2018 and 2021. The SDT model was constructed to segment patients into different risk groups, and their recurrence-free survival (RFS) probabilities were compared using the log-rank test. We compared the SDT with the Cox proportional hazards model and random survival forest (RSF). Model performance was assessed using the c-index, calibration intercept and slope, and integrated Brier score.

RESULTS

A total of 5,919 patients diagnosed with invasive breast cancer were analyzed, and four risk groups were identified: low risk, medium risk, high risk, and very high risk. There was a significant difference in RFS across groups (
P
< .001). The pruned SDT model showed similar or better performance than the benchmarking methods; however, the RSF may be useful in the subgroup of patients with two or more comorbidities, where a more complex relationship may exist.

CONCLUSION
Risk stratification can be accurately modeled via a tree-based method. Future research should layer in other outcomes, such as comorbidity, ongoing treatment toxicities, or risk of delayed treatment, to improve risk-stratified care and effective use of health care resources.
Impact of Psychological Factors on Survival in Metastatic Esophagogastric Cancer: Secondary Analysis of a Randomized Controlled Trial
Authors: Song Lili , Pang Ying , He Yi , Lu Zhihao , Fang Yu , Zhang Xiaotian , Cao Yanshuo , Jiao Xi , Zhou Jun , Qi Changsong , Gong Jifang , Wang Xicheng , Li Jian , Liu Chang , Tang Lili 
Published: January 2025

PURPOSE
Early interdisciplinary supportive care (ESC), including psychological interventions, can improve the survival of patients with metastatic esophagogastric cancer (EGC). The purpose of the study was to evaluate the association between psychological factors and survival in patients with metastatic EGC.

METHODS
A secondary analysis was conducted for an open-label randomized controlled trial of ESC, in which 246 patients with EGC completed a distress measure (the distress thermometer) and a depression symptom measure (the Patient Health Questionnaire-9 [PHQ-9]) at baseline before cancer treatments. Cox regression was applied to explore the influence of psychological distress and depressive symptoms on overall survival (OS) and progression-free survival (PFS).

RESULTS

Patients with moderate depressive symptoms (PHQ-9 ≥8) had shorter PFS (3.5
v
6.0 months,
P
< .001) and shorter OS (10.7
v
15.0 months,
P
= .001) than those without. Patients with significant psychological distress had worse PFS (4.8
v
6.3 months,
P
= .035) and worse OS (13.4
v
15.5 months,
P
= .039) than those without. After controlling for performance status, group, sex, primary tumor site, tumor histology, and age, only depressive symptoms remained associated with worse PFS (adjusted hazard ratio [HR], 2.02 [95% CI, 1.41 to 2.91];
P
< .001) and worse OS (adjusted HR, 1.70 [95% CI, 1.17 to 2.47];
P
= .006).

CONCLUSION
This study shows that depressive symptoms at baseline were associated with poor survival in patients with newly diagnosed metastatic EGC. Therefore, screening and preventive intervention for depression should be integrated into routine cancer care for this population.
Stereotactic Radiosurgery for World Health Organization Grade 2 and 3 Oligodendroglioma: An International Multicenter Study
Authors: Langlois Anne-Marie , Iorio-Morin Christian , Kallos Justiss , Niranjan Ajay , Lunsford L. Dade , Peker Selcuk , Samanci Yavuz , Park David J. , Barnett Gene H. , Liscak Roman , Simonova Gabriela , Pikis Stylianos , Mantziaris Georgios , Sheehan Jason , Lee Cheng-chia , Yang Huai-che , Bowden Greg N. , Mathieu David 
Published: January 2025

BACKGROUND AND OBJECTIVES:
Oligodendrogliomas are primary brain tumors classified as isocitrate deshydrogenase–mutant and 1p19q codeleted in the 2021 World Health Organization Classification of central nervous system tumors. Surgical resection, radiotherapy, and chemotherapy are well-established management options for these tumors. Few studies have evaluated the efficacy of stereotactic radiosurgery (SRS) for oligodendroglioma. As these tumors are less infiltrative than astrocytomas and typically recur locally, focal therapy such as SRS is an appealing option.

METHODS:
This study was performed through the International Radiosurgery Research Foundation. The objective was to collect retrospective multicenter data on tumor control, clinical response, and morbidity after SRS for oligodendroglioma. Inclusion criteria were age of 18 years or more, single-fraction SRS, and histological confirmation of grade 2 or 3 oligodendroglioma. The primary end points were progression-free survival (PFS) and overall survival from SRS. Secondary end points included clinical evolution and occurrence of adverse radiation events or other complications. Descriptive statistics, Kaplan–Meier analyses, and univariate and multivariate analyses were performed.

RESULTS:
Eight institutions submitted data for a total of 55 patients. The median follow-up time was 24 months. The median age at SRS was 46 years, and the median Karnofsky Performance Status was 90%. The median marginal dose used was 15 Gy. The median PFS was 17 months, with actuarial rates of 60% at 1 year, 31% at 2 years, and 24% at 5 years after SRS. Factors significantly associated with worsened PFS were World Health Organization grade 3, previous radiotherapy and chemotherapy, and higher marginal dose. The median overall survival post-SRS was 58 months, with actuarial rates of 92% at 1 year, 83% at 2 years, and 49% at 5 years. Karnofsky Performance Status remained stable post-SRS in 51% and worsened in 47% of patients, most often because of tumor progression (73%). Radiation-induced changes occurred in 30% of patients, of which only 4 were symptomatic.

CONCLUSION:
SRS is a reasonable management option for patients with oligodendroglioma.
N-acetylglutamate synthetase deficiency - literature review
Authors: Wdowiak Krystian , Maciocha Agnieszka , Wąż Julia , Witas Aleksandra , Drogoń Justyna , Chachaj Weronika , Szymkowiak Natalia , Gardocka Ewa 
Published: January 2025

Introduction and Objective: N-Acetylglutamate Synthetase Deficiency (NAGSD) is a rare urea cycle disorder, primarily caused by autosomal recessive genetic mutations. Most affected individuals are homozygous for the disease-causing allele. The aim of this publication is to discuss various aspects of N-acetylglutamate synthetase deficiency based on the latest literature.Review Methods: The PubMed database was searched to find scientific articles in which the terms "N-acetylglutamate synthetase," "NAGS deficiency," or "N-acetylglutamate synthetase deficiency" appear in the title, abstract, or keywords.Brief Description of the State of Knowledge: Symptoms of NAGSD typically appear in the neonatal period. The NAGS enzyme is essential for catalyzing the synthesis of N-acetylglutamate, an allosteric activator of carbamoylphosphate synthetase 1 (CPS1), crucial for the urea cycle. Key biochemical markers include elevated ammonia, glutamine, and alanine; decreased citrulline; and respiratory alkalosis. Hyperammonemia is the main clinical feature, manifesting as nausea, vomiting, cognitive impairment, seizures, and, in severe cases, coma or death. Genetic testing remains the cornerstone of diagnosis, enabling identification of specific mutations. Treatment involves carbamylglutamate, an NAG analog that activates CPS1.Summary: Expanding research aims to explore novel treatments in NAGSD, dietary strategies, and the safety of current therapies during pregnancy.