bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and Mechanistic DFT Studies of Arylhimachalene via
Bromination of Himachalenes
Authors: Faris A. , Louchachha I. , Edder Y. , Mansour A.A. , Boualy B. , Salghi R. , Karim A. 
Published: January 2025

Background:
Arylhimachalene is a sought-after natural sesquiterpene, found in small
quantities in the essential oil of Atlas cedar (Cedrus atlantica). Herein, we present a simple and efficient
method for synthesizing this molecule, involving the bromination of a mixture of himachalene
(the principal constituent of the same oil) and a mechanistic study based on density functional theory
(DFT) calculations.

Methods:
The synthesis of arylhimachalene was carried out by bromination using Br2/CH2Cl2. The
resulting product was isolated by silica gel column chromatography and characterized by NMR spectroscopy.

Results:
The treatment of the himachalene mixture with bromine led to the formation of arylhimachalene,
as well as other rearrangement products catalyzed by in situ-formed bromic acid.

Conclusion:
This study highlights the development of a simple method for synthesizing a natural
molecule of interest, serving as a basis for numerous scientific studies, and also includes a mechanistic
study of this synthesis.
SPIONs: Paving the Way for Targeted Drug Delivery to Cancer Cells
Authors: Mollick Mirazuddin , Rahaman Syed Mustafizur , Ashique Sumel , Bhowmick Mithun , Bhowmick Pratibha , Pal Radheshyam , Kumar Prashant 
Published: January 2025

Abstract:
Superparamagnetic iron oxide nanoparticles have gained considerable attention in drug
delivery due to their superparamagnetic characteristics. SPIONs have a greater surface-to-volume
ratio, size, superficial chemistry, and superparamagnetic characteristics, which allow them to be
covered by external magnetic fields. These properties make SPIONs promising nanoparticles for
drug delivery systems. A great advantage of the superparamagnetic characteristics is magnetic
properties. SPIONs are magnetic and thoroughly demagnetized when the field of the electromagnet
is pulled out. These characteristics permit their targeted delivery to a particular tissue or cell
following a magnetic field. Furthermore, SPIONs can be fabricated with particular ligands, such
as peptides or antibodies, to increase their efficiency in desired cells or tissues. This permits delivery,
particularly to the desired cell type, increases therapeutic activity, and reduces off-target effects.
Moreover, SPIONs exhibit imaging characteristics. However, this review highlights the capabilities
of SPIONs for targeted drug delivery to reduce tumor cell toxicity.
Serum Cortisol and Cardiovascular Disease Risk-A Potential Biomarker
Authors: Oo Wei Jet , Lim Chooi Ling , Goh Mun Hon , Koh Rhun Yian 
Published: January 2025

Abstract:
Cardiovascular Disease [CVD], the leading cause of death globally, poses a
significant burden on the healthcare sector. Its association with stress and Cushing’s Syndrome
has driven cortisol, the ‘stress hormone,’ to be a potential candidate in determining CVD risk.
Cortisol synthesis and release through the hypothalamic-pituitary-adrenal [HPA] axis are
regulated by several hormones and receptors involved in the pathological cascade towards CVD.
Evidence suggests that metabolic syndrome plays a major role in cortisol-mediated CVD risk.
On the other hand, non-metabolic features are also implicated when the association between
cortisol and CVD risk remains significant upon normalisation of metabolic parameters.
Correspondingly, the treatment for hypercortisolism is often found effective in lowering CVD
risk. Despite available evidence, several factors continue to hinder the clinical use of cortisol as
a risk biomarker for CVD. This review provides an insight into the role of serum cortisol in
CVD progression and risk, with emphasis on the mechanistic features and parameters.
Identification, Isolation, Structure Characterization, and Chromatographic Separation of a New Highly Analogous Impurity of the Ubrogepant
Authors: Ummiti Kumarswamy , Vanga Nagavardhana Reddy 
Published: January 2025

Background:
Ubrogepant is a regulated peptide receptor antagonist associated with the
calcitonin gene, granted approval in the United States for the specific treatment of migraine
headaches.

Objective:
An impurity found in the alkali hydrolysis of drug dosage forms has a structure very similar
to that of ubrogepant. This research aims to characterize this analogous impurity utilizing NMR
and LC-MS spectroscopy tools. Moreover, it is critical to develop an extremely sensitive and
superior resolution analytical procedure for identifying and determining the amount of analogous
impurity in pharmaceutical products.

Method:
The ubrogepant impurity was identified using an optimized chromatographic method that
relies on reversed-phase HPLC with UV detection. This technique utilized a charged surface hybrid
(CSH) technology column operating in gradient elution mode. A mixture of A-channel (0.1%
trifluoroacetic acid) and B-channel (acetonitrile and water, 80:20% v/v) constituted the eluent. The
analogous impurity was isolated through fraction collection, purified using flash chromatography,
and characterized using NMR (1D and 2D) and LC-MS.

Results:
The analogous impurity was successfully separated from the ubrogepant peak with a resolution
above 2.0. The concentration of the impurity was approximately 10% compared to the ubrogepant
peak after alkaline stressing at room temperature for 30 minutes. NMR (1D 13C NMR and
1H, 2D HMBC, HSQC, NOESY, and COSY) and LC-MS analysis characterized the ubrogepant
impurity, revealing it to be an epimer of ubrogepant. The developed approach was highly sensitive,
allowing for the quantification of the ubrogepant impurity even at a concentration of 0.2 μg/mL.

Conclusion:
The approach demonstrated a remarkable degree of precision, linearity, specificity, and
accuracy. This new impurity deserves special attention because of its striking similarity to the active
ingredient, ubrogepant.
Synthesis of Hydrazides Derivatives as Anti-Mycobacterial Agents Mediated by the Environmental-Friendly Organocatalyst
Authors: Nongkhlaw Ridahunlang , Nongrum Ridaphun , Sriram Dharmarajan , Kumari Jyothi , Nongkhlaw Rishanlang 
Published: January 2025

Background:
Hydrazide derivatives were synthesized using an organocatalyst, offering an environmentally friendly approach characterized by shorter reaction times, mild conditions, and the use of green solvents.

Objective:
The objective was to evaluate the synthesized compounds for their anti-tubercular ac-tivity against Mycobacterium tuberculosis (Mtb) and to assess the cytotoxicity of active com-pounds using the MTT assay.

Methods:
Ultrasound energy was employed to facilitate the synthesis of the compounds. The re-sulting compounds were tested for their activity against Mycobacterium tuberculosis (Mtb), and the active compounds were further evaluated for cytotoxicity using the 3-(4,5-dimethylthiazol-2-yl) -2,5- diphenyl tetrazolium bromide MTT assay.

Results:
Several compounds demonstrated activity against Mtb, with some derivatives exhibiting a Minimum Inhibitory Concentration (MIC) of 1.56 μg/mL, comparable to the standard anti-tu-bercular drug Ethambutol.

Conclusion:
The eco-friendly synthesis of hydrazide derivatives shows significant potential in the development of anti-tubercular agents, with some compounds displaying efficacy similar to estab-lished drugs.
Rice husk ash-based selective absorbent with imprinted ionic for gold recovery
Authors: Hastuti Sri , Fajariani Ema N. , Candraningrum Intan K. , Martini Tri , Wahyuningsih Sayekti , Aini Fitri N. 
Published: January 2025

The recovery of gold from aqueous solutions is crucial due to its economic value and environmental significance, making effective separation technologies essential. To tackle this challenge, development of an adsorbent with enhanced selectivity and high adsorption capacity against Au(III) is highly crucial. This present study harnessed rice husk derived-silica functionalized by (3-trimethoxysilyl)propyldiethylenetriamine (TMPDT) using imprinted ionic method to form SiO2-TMPDT-Au-Imp, specifically designed for the selective adsorption of Au(III). SiO2-TMPDT-Au-Imp demonstrated a significantly higher adsorption capacity about 387% improvement compared to SiO2-TMPDT, highlighting its superior performance. Furthermore, in addition to exhibit several advantageous characteristics that surpass those of other materials tested, underscoring its effectiveness in Au(III) adsorption. SiO2-TMPDT-Au-Imp displayed notable selectivity in competitive metal ion solutions with the preference order of Au(III)/Fe(III) < Au(III)/Cu(II) < Au(III)/Zn(II). The developed SiO2-TMPDT-Au-Imp, in brief, represents a promising advancement in the field of material science and environmental remediation in which it offers a tailored solution for efficient and selective adsorption of Au(III). This study can also be applied for the recovery of Au(III) ions from electronic waste.
Annealing temperature modify of crystalline structure, magnetic properties and antibacterial performance in nickel substituted cobalt ferrite nanoparticles utilizing natural-fine-sediment
Authors: Bestari Laksmita Farah , Iqlimatussholihah Lathifah , Prasetya Nurdiyantoro Putra , Kusumandari  , Utari  , Riyatun  , Purnama Budi 
Published: January 2025

This study details the nickel-substituted cobalt ferrite nanoparticle employing natural fine sediment (NiCFO-fs) annealing temperature dependency of crystalline and magnetic characteristics. The NiCFO-fs nanoparticles were prepared by the coprecipitation method with varying annealing temperatures (200-500°C with increment of 100°C for five hours). As a comparison, Ni-CFO was also synthesized using pure analytical chemicals (NiCFO-pa). The XRD results showed that the whole Ni-CFO nanoparticles established an inverse spinel face center cubic (fcc) order according to space group Fd-3m for both NiCFO-fs and NiCFO-pa. There was no additional peak, indicating that Ni2+ cations successfully substituted in cobalt ferrite nanoparticles. In case of NiCFO-fs nanoparticle samples, a crystallite size (D) decreased with the increasing annealing temperature (Ta), namely 45.72 nm, 37.35 nm, 25.95 nm, and 20.51 nm. In contrast to NiCFO-pa, the D increased with the increase of the Ta, i.e., 19.67 nm, 20.74 nm, 21.99 nm, and 23.33 nm. Meanwhile, FTIR results showed the presence of metal-oxygen bonds at 551-586 cm-1 and 384-391 cm-1 at tetrahedral (k1) and the octahedral (k2) sites for both NiCFO-fs and NiCFO-pa nanoparticles samples. The VSM result showed that a narrow hysteresis curve was observed for the NiCFO-fs sample compared to NiCFO-pa. The NiCFO-fs nanoparticles owing the smallest coercive field (HC) of 79.5 Oe were attained for the Ta of 300°C. In case of NiCFO-fs samples, magnetization saturation (MS) decreased with the increase of the Ta in contrast to NiCFO-pa samples. Here, the redistribution of two and three plus ions in the sub-lattice k1 and k2 locations should be encouraged by the Jahn-Teller phenomenon through strain-induced magnetism. The findings of the antibacterial test indicated that the potential of NiCFO based on natural materials (fine sediment) was higher than that of NiCFO based on pure analytical chemicals. This result was also supported by the emergence of ZOI magnitudes for all NiCFO-fs materials compared to NiCFO-pa that was only at Ta = 300°C.
Nitrogen fertilizer use reduction by two endophytic diazotrophic bacteria for soil nutrients and corn yield
Authors: Chuong Nguyen Van , Nguyen Ngoc Phuong Trang , Nguyen Van Thuan 
Published: January 2025

Today, the utilization of endophytic diazotrophic bacteria (EDB) purposely to minimize the application of urea fertilizer (UF), and enhance soil fertility, crop quality and corn yield in sustainable agricultural practices is an inevitable trend. The experiment was arranged outside the AGU green house of Agriculture Research Center, An Giang university, Vietnam, which consisted of two factors: (i) two EDB species [Bacillus sp. NTLG2-20 (Bacillus A) and Bacillus arybhattai strain CM44 (Bacillus B)] and (ii) three UF ratios (0.0, 100 and 200 kg N ha-1) and four replications. Research data presented that the fresh cob yield of Bacillus A was found 4.0% higher than that of Bacillus B and 12.7% than that of non EDB inoculation. Furthermore, the inoculation of Bacillus B had 9.02% higher fresh cob yield compared to non-inoculation. The 50% reduction of UF application combined EDB addition obtained the fresh cob with no significant difference, compared to 100% recommended urea application. The interaction between the effectiveness of EDB inoculation and UF reduction was clearly different in favor of corn grown on sandy loam soils with low nutrient contents. Both Bacillus A and Bacillus B had the abilities of high yield and good nitrogen fixation with the potential to simultaneously improve soil fertility and corn yield. The results of this study demonstrated that two strains of Bacillus A and Bacillus B have the potential to promote the growth and increase the yield of peanuts, and it should be suggested for future biological fertilizer production.
Transforming Informed Consent Generation Using Large Language Models: Mixed Methods Study
Authors: Shi Qiming , Luzuriaga Katherine , Allison Jeroan J , Oztekin Asil , Faro Jamie M , Lee Joy L , Hafer Nathaniel , McManus Margaret , Zai Adrian H 
Published: January 2025

Abstract

Background
Informed consent forms (ICFs) for clinical trials have become increasingly complex, often hindering participant comprehension and engagement due to legal jargon and lengthy content. The recent advances in large language models (LLMs) present an opportunity to streamline the ICF creation process while improving readability, understandability, and actionability.

Objectives
This study aims to evaluate the performance of the Mistral 8x22B LLM in generating ICFs with improved readability, understandability, and actionability. Specifically, we evaluate the model’s effectiveness in generating ICFs that are readable, understandable, and actionable while maintaining the accuracy and completeness.

Methods
We processed 4 clinical trial protocols from the institutional review board of UMass Chan Medical School using the Mistral 8x22B model to generate key information sections of ICFs. A multidisciplinary team of 8 evaluators, including clinical researchers and health informaticians, assessed the generated ICFs against human-generated counterparts for completeness, accuracy, readability, understandability, and actionability. Readability, Understandability, and Actionability of Key Information indicators, which include 18 binary-scored items, were used to evaluate these aspects, with higher scores indicating greater accessibility, comprehensibility, and actionability of the information. Statistical analysis, including Wilcoxon rank sum tests and intraclass correlation coefficient calculations, was used to compare outputs.

Results
LLM-generated ICFs demonstrated comparable performance to human-generated versions across key sections, with no significant differences in accuracy and completeness (P>.10). The LLM outperformed human-generated ICFs in readability (Readability, Understandability, and Actionability of Key Information score of 76.39% vs 66.67%; Flesch-Kincaid grade level of 7.95 vs 8.38) and understandability (90.63% vs 67.19%; P=.02). The LLM-generated content achieved a perfect score in actionability compared with the human-generated version (100% vs 0%; P<.001). Intraclass correlation coefficient for evaluator consistency was high at 0.83 (95% CI 0.64-1.03), indicating good reliability across assessments.

Conclusions
The Mistral 8x22B LLM showed promising capabilities in enhancing the readability, understandability, and actionability of ICFs without sacrificing accuracy or completeness. LLMs present a scalable, efficient solution for ICF generation, potentially enhancing participant comprehension and consent in clinical trials.
Targeting Toll-like receptor 4 and microbiota dysregulation: a new frontier in nonalcoholic fatty liver disease management
Authors: Kvit K.B. 
Published: January 2025

Background. Nonalcoholic fatty liver disease (NAFLD) is a widespread chronic liver condition affecting nearly a quarter of the global population. It encompasses a spectrum of disorders, ranging from simple steatosis to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, often associated with metabolic syndrome and insulin resistance. Emerging evidence underscores the critical role of gut microbiota dysbiosis and Toll-like receptor 4 (TLR4) activation in the pathogenesis and progression of NAFLD. Gut-derived lipopolysaccharides activate TLR4, initiating inflammatory cascades that exacerbate liver injury. This study purposed to evaluate the relationship between gut microbiota composition, TLR4 levels, and biochemical markers in NAFLD and to assess the efficacy of microbiome-targeted therapy in modulating these factors. Materials and methods. The study included 152 patients with NAFLD and 47 control participants without liver steatosis. NAFLD diagnosis was confirmed by ultrasound, steatometry, and the presence of cardiometabolic risk factors. Microbiota composition was analyzed using quantitative polymerase chain reaction, and TLR4 levels were measured in serum samples. Patients with NAFLD underwent a microbiome-targeted therapy consisting of rifaximin, probiotics, and essential phospholipids over 12 weeks. Biochemical, microbiota, and inflammatory markers were assessed before and after treatment. Statistical analyses included t-tests and correlation analysis to explore associations between microbiota, TLR4, and biochemical parameters. Results. Patients with NAFLD exhibited significant gut microbiota changes, characterized by an increased Firmicutes/Bacteroidetes ratio and elevated Actinobacteria levels compared to controls. TLR4 levels were significantly higher in the NAFLD group, correlating positively with liver function tests and systemic inflammatory markers. Following microbiome-targeted therapy, patients demonstrated a substantial reduction in TLR4 levels, improved liver enzymes (alanine aminotransferase, aspartate aminotransferase), decreased HOMA-IR index, and enhanced gut microbiota composition. Notably, the prevalence of small intestinal bacterial overgrowth decreased from 51 to 20 %. Conclusions. The findings emphasize the critical role of gut microbiota dysbiosis and TLR4 activation in the progression of NAFLD. Microbiome-targeted therapy proved effective in reducing TLR4-driven inflammation, improving metabolic and liver function, and normalizing dysbiotic microbial profiles, supporting the use of microbiota-focused interventions in NAFLD management.
Studying red cell distribution width in Iraqi persons with type 2 diabetes mellitus in Najaf City: a case-control study
Authors: Hussein Alaasam Maysam Riyadh Mohammed , Abbas Al-buthabhak Karrar Mohammed , Mech Ahmed , Hussein Shamim Riadh Mohammed 
Published: January 2025

Background. Red cell distribution width (RDW) is a parameter measured routinely in standard blood cell counts, reflecting the variability in red cell size and volume. Numerous studies have identified a significant correlation between RDW and various health disorders, including cardiovascular diseases, malignancies, obesity, and chronic kidney diseases. Purpose: to study red cell distribution width in Iraqi persons with type 2 diabetes and assess its role in providing clinical information about glycemic control. Materials and methods. This case-control study included 300 participants, 150 Iraqi persons with type 2 diabetes (77 female and 73 male) in Najaf City, and 150 healthy controls (79 female and 71 male). Age, weight, systolic blood pressure, diastolic blood pressure, complete blood count, glycated hemoglobin (HbA1c), and C-reactive protein levels were assessed. In patients with diabetes, disease duration, medications, and complications were recorded. People with a history of anemia, renal failure, heart disease, hypertension, thyroid disorder, pregnancy, and conditions leading to chronic inflammation, such as rheumatoid arthritis, diabetic neuropathy, diabetic retinopathy, and diabetic nephropathy, were excluded from the study. Results. RDW was significantly higher in people with diabetes (14.77 ± 3.56) than in healthy controls (12.19 ± 1.10), p < 0.0001. In the diabetes group, no statistically significant correlation was noted between RDW and disease duration (p = 0.143). RDW was strongly and directly associated with HbA1c and C-reactive protein levels (p < 0.0001 and р = 0.002, respectively). Conclusions. RDW was higher in people with type 2 diabetes than in healthy controls. RDW levels are affected by glycemic control because a higher HbA1c level is associated with a higher RDW. Thus, RDW can be considered a marker of glycemic control in clinical practice.
The role of endogenous insulin in patients with acute pancreatitis
Authors: Dronov O.I. , Kovalska I.O. , Ivanets T.Yu. , Kozachuk Ye.S. , Levchenko L.V. , Stasiuk U.V. 
Published: January 2025

Background. Acute pancreatitis is an inflammatory disease of the exocrine part of the pancreas, accompanied by various complications and further development of necrosis of the gland and parapancreatic tissue with possible secondary infection. The study of experimental models shows that the acinar cells surrounding the islets of Langerhans remain relatively intact, indicating that endogenous insulin is a protective factor for the pancreatic parenchyma. The purpose of the study was to determine the dependence of endogenous insulin levels on the extent of pancreatic parenchymal damage. Materials and methods. Prospective analysis of endogenous insulin levels in 51 patients with acute pancreatitis. Results. Comparison of the mean values of endogenous insulin revealed that in patients with necrotizing pancreatitis, the median value was statistically significantly lower than in patients without pancreatic necrosis (p < 0.001). Moreover, in pancreatic necrosis, the determined level of endogenous insulin did not exceed 9 mcIU/ml and in 7 (13.7 %) patients, insulin was below the reference values. ROC analysis showed that low endogenous insulin is a risk factor for pancreatic necrosis. The threshold value of endogenous insulin, at which pancreatic necrosis was most often diagnosed, was determined, cut-off value of 5.3 mcIU/ml, AUC of 0.96 (95% CI 0.92–1.00) (sensitivity 91.89 % (95% CI 78.09–98.3 %), specificity 71.43 % (95% CI 41.9–91.61 %), PPV 89.47 % (95% CI 78.69–95.14 %), NPV 76.92 % (95% CI 51.74–91.2 %)). Conclusions. There was a statistically significant difference between the mean insulin values depending on the volume and location of pancreatic parenchymal damage (p < 0.001). In patients without pancreatic necrosis, endogenous insulin was statistically significantly higher than in those with pancreatic necrosis (p < 0.001). Binomial logistic regression analysis showed that the development of pancreatic necrosis in patients with acute pancreatitis significantly depended on the values of endogenous insulin at hospitalization. The level of endogenous insulin may be an additional indicator of the acute pancreatitis severity and the formation of necrotic changes in the pancreatic tissue, which will allow for correct initiation of treatment.