bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of High Altitude Environment on Pharmacokinetic and
Pharmacodynamic of Warfarin in Rats
Authors: Zhang Xiaojing , Mu Hongfang , Zhong Yan , Wang Rong , Li Wenbin 
Published: February 2024

Background:
High altitude environment affects the pharmacokinetic (PK) parameters of drugs and
the PK parameters are an important theoretical basis for guiding the rational clinical use of drugs. Warfarin is
an oral anticoagulant of the coumarin class commonly used in clinical practice, but it has a narrow therapeutic
window and wide individual variation. However, the effect of high altitude environment on PK and pharmacodynamic
(PD) of warfarin is unclear.

Objective:
The objective of this study is to investigate the effect of a high altitude environment on PK and PD
of warfarin in rats.

Method:
Rats were randomly divided into plain group and high altitude group and blood samples were collected
through the orbital venous plexus after administration of 2 mg/kg warfarin. Warfarin concentrations in plasma
samples were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and PK parameters
were calculated by the non-compartment model using WinNonlin 8.1 software. Meanwhile, the expression
of PXR, P-gp and CYP2C9 in liver tissues was also determined by western blotting. The effect of
high altitude environment on PD of warfarin was explored by measuring activated partial thromboplastin time
(APTT) and prothrombin time (PT) values and then calculated international normalized ratio (INR) values
based on PT.

Results:
Significant changes in PK behaviors and PD of warfarin in high altitude-rats were observed. Compared
with the plain-rats, the peak concentration (Cmax) and the area under the plasma concentration-time curve
(AUC) increased significantly by 50.9% and 107.46%, respectively. At the same time, high altitude environment
significantly inhibited the expression of PXR, P-gp and CYP2C9 in liver tissues. The results of the PD
study showed that high altitude environments significantly prolonged PT, APTT and INR values.

Conclusion:
High altitude environment inhibited the metabolism and increased the absorption of warfarin in
rats and increased the effect of anticoagulant effect, suggesting that the optimal dose of warfarin for patients at
high altitude should be reassessed.
Surface Functionalized Lipid Nanoparticles in Promoting Therapeutic
Outcomes: An Insight View of the Dynamic Drug Delivery System
Authors: Manchanda Namish , Vishkarma Harish , Goyal Muskan , Shah Saurabh , Famta Paras , Talegaonkar Sushama , Srivastava Saurabh 
Published: February 2024

Abstract:
Compared to the conventional approach, nanoparticles (NPs) facilitate a non-hazardous,
non-toxic, non-interactive, and biocompatible system, rendering them incredibly promising
for improving drug delivery to target cells. When that comes to accomplishing specific therapeutic
agents like drugs, peptides, nucleotides, etc., lipidic nanoparticulate systems have emerged as
even more robust. They have asserted impressive ability in bypassing physiological and cellular
barriers, evading lysosomal capture and the proton sponge effect, optimizing bioavailability, and
compliance, lowering doses, and boosting therapeutic efficacy. However, the lack of selectivity at
the cellular level hinders its ability to accomplish its potential to the fullest. The inclusion of surface
functionalization to the lipidic NPs might certainly assist them in adapting to the basic biological
demands of a specific pathological condition. Several ligands, including peptides, enzymes,
polymers, saccharides, antibodies, etc., can be functionalized onto the surface of lipidic NPs to
achieve cellular selectivity and avoid bioactivity challenges. This review provides a comprehensive
outline for functionalizing lipid-based NPs systems in prominence over target selectivity. Emphasis
has been put upon the strategies for reinforcing the therapeutic performance of lipidic nano
carriers' using a variety of ligands alongside instances of relevant commercial formulations.
Proteomic Analysis of the Molecular Mechanisms of Chlorpromazine
Inhibiting Migration of Oral Squamous Cell Carcinoma
Authors: Zhang Nannan , Liu Junzhi , Dong Qiuping , Liu Chen , Liang Xinyu , Tang Peiyuan , Liang Zheng 
Published: February 2024

Background:
Oral squamous cell carcinoma (OSCC) is a common malignant tumor of
the head and neck region known for its high metastatic and invasive potential. Chlorpromazine
(CPZ) has been shown to inhibit the growth of oral cancer cells. However, the effects of CPZ on
OSCC migration and its underlying molecular mechanisms remain unclear.

Objective:
We aimed to identify global protein changes and potential core proteins involved in
CPZ-mediated inhibition of migration in SCC-15 cells using proteomics.

Methods:
We assessed the effect of CPZ on SCC-15 using CCK-8 assays and wound healing experiments.
Next, we performed LC-MS-based proteomic analysis to identify protein alterations in
SCC-15 cells treated with CPZ at different times. Differential expression proteins (DEPs) were
identified and subjected to bioinformatics analysis using GO, KEGG, and PPI tools. Key candidate
proteins were selected and validated using the TCGA-HNSCC database and molecular docking.

Results:
It was found that 20μm of CPZ had no effect on cell proliferation, but inhibited cell migration.
A total of 4748 proteins were identified by Proteomics, among which 56 DEPs were identified,
including 34 upregulated proteins and 22 downregulated proteins. Three proteins (RPF2,
ACTB, and TGFBI) were identified as key candidate proteins associated with cell adhesion and
migration in oral cancer cells.

Conclusion:
CPZ may affect the expression of RPF2, ACTB, and TGFBI proteins and change the
extracellular matrix and cell adhesion function, thus inhibiting the migration of SCC-15 cells. The
results of this study provide a robust basis for further research on the molecular mechanism of
CPZ to inhibit the migration of OSCC.
Nanotechnology-based Approaches for Breast Cancer
Authors: Prabha Shashi , Kumar Panda Pritish , Singh Sumita , Ahmed Bahar 
Published: February 2024

Abstract:
One common cancer among women is breast cancer. Chemotherapy, radiation therapy, and
surgery have historically been used as breast cancer treatments. Thanks to recent technological advancements,
we have been able to progressively comprehend the complexity and heterogeneity of
diseases, which has led to the development of more effective treatments for many conditions. Working
with variably shaped nanoparticles, nanotechnology has recently enabled us to work on tumor
targeting and drug delivery, and it has undoubtedly helped to reduce the spread and death of breast
cancer. The efficacy of treatment for breast cancer can be increased by a variety of target therapies
made possible by nanotechnology. The current review discusses the advantages and disadvantages of
nanotechnology-based therapy for breast cancer while also highlighting the disease's current state.
The article will provide an overview of the current strategy available for better treatment of breast
cancer and aid in understanding the various drug delivery systems designed to provide effective
treatment for the disease. By utilizing cutting-edge technologies and early screening, breast cancer
fatalities can be decreased. Drug delivery methods based on nano carriers enable medication to reach
the target site at the ideal concentration with the least amount of harmful side effects.
Catalyst-free Aloe Vera-promoted Cyclization of 2-Amino-azarenes with Phenacyl Bromide
Authors: Baranwal Jyoti , Singh Swastika , Kushwaha Smriti , Jyoti Archana 
Published: February 2024

Introduction:
By condensing 2-aminothiazole and phenacyl bromide, a novel catalystfree
synthetic approach for the synthesis of imidazo[2,1-b]thiazole derivatives has been developed.

Methods:
In this work, aloe vera/water (3:2) is used as a reusable, environmentally benign, greenpromoting
media to synthesize desired products. This method enables the synthesis of a diverse
range of aryl-substituted imidazo[2,1-b]thiazoles.

Results:
This solvent system demonstrates remarkable efficiency and offers numerous advantages,
including shorter reaction times, the absence of side product formation, costeffectiveness,
excellent atom efficiency, straightforward operation, and high yields.

Conclusion:
In conclusion, we successfully developed a green protocol for the environmentally
benign synthesis of imidazo[2,1-b]thiazole derivatives using aloe vera water as green-promoting
media.
Attrition Rates in HIV Viral Load Monitoring and Factors Associated With Overdue Testing Among Children Within South Africa’s Antiretroviral Treatment Program: Retrospective Descriptive Analysis
Authors: Haeri Mazanderani Ahmad , Radebe Lebohang , Sherman Gayle G 
Published: February 2024

Background
Numerous studies in South Africa have reported low HIV viral load (VL) suppression and high attrition rates within the pediatric HIV treatment program.

Objective
Using routine laboratory data, we evaluated HIV VL monitoring, including mobility and overdue VL (OVL) testing, within 5 priority districts in South Africa.

Methods
We performed a retrospective descriptive analysis of National Health Laboratory Service (NHLS) data for children and adolescents aged 1-15 years having undergone HIV VL testing between May 1, 2019, and April 30, 2020, from 152 facilities within the City of Johannesburg, City of Tshwane, eThekwini, uMgungundlovu, and Zululand. HIV VL test–level data were deduplicated to patient-level data using the NHLS CDW (Corporate Data Warehouse) probabilistic record-linking algorithm and then further manually deduplicated. An OVL was defined as no subsequent VL determined within 18 months of the last test. Variables associated with the last VL test, including age, sex, VL findings, district type, and facility type, are described. A multivariate logistic regression analysis was performed to identify variables associated with an OVL test.

Results
Among 21,338 children and adolescents aged 1-15 years who had an HIV VL test, 72.70% (n=15,512) had a follow-up VL test within 18 months. Furthermore, 13.33% (n=2194) of them were followed up at a different facility, of whom 3.79% (n=624) were in a different district and 1.71% (n=281) were in a different province. Among patients with a VL of ≥1000 RNA copies/mL of plasma, the median time to subsequent testing was 6 (IQR 4-10) months. The younger the age of the patient, the greater the proportion with an OVL, ranging from a peak of 52% among 1-year-olds to a trough of 21% among 14-year-olds. On multivariate analysis, 2 consecutive HIV VL findings of ≥1000 RNA copies/mL of plasma were associated with an increased adjusted odds ratio (AOR) of having an OVL (AOR 2.07, 95% CI 1.71-2.51). Conversely, patients examined at a hospital (AOR 0.86, 95% CI 0.77-0.96), those with ≥2 previous tests (AOR 0.78, 95% CI 0.70-0.86), those examined in a rural district (AOR 0.63, 95% CI 0.54-0.73), and older age groups of 5-9 years (AOR 0.56, 95% CI 0.47-0.65) and 10-14 years (AOR 0.51, 95% CI 0.44-0.59) compared to 1-4 years were associated with a significantly decreased odds of having an OVL test.

Conclusions
Considerable attrition occurs within South Africa’s pediatric HIV treatment program, with over one-fourth of children having an OVL test 18 months subsequent to their previous test. In particular, younger children and those with virological failure were found to be at increased risk of having an OVL test. Improved HIV VL monitoring is essential for improving outcomes within South Africa’s pediatric antiretroviral treatment program.
Mining Clinical Notes for Physical Rehabilitation Exercise Information: Natural Language Processing Algorithm Development and Validation Study
Authors: Sivarajkumar Sonish , Gao Fengyi , Denny Parker , Aldhahwani Bayan , Visweswaran Shyam , Bove Allyn , Wang Yanshan 
Published: February 2024

Background
The rehabilitation of a patient who had a stroke requires precise, personalized treatment plans. Natural language processing (NLP) offers the potential to extract valuable exercise information from clinical notes, aiding in the development of more effective rehabilitation strategies.

Objective
This study aims to develop and evaluate a variety of NLP algorithms to extract and categorize physical rehabilitation exercise information from the clinical notes of patients who had a stroke treated at the University of Pittsburgh Medical Center.

Methods
A cohort of 13,605 patients diagnosed with stroke was identified, and their clinical notes containing rehabilitation therapy notes were retrieved. A comprehensive clinical ontology was created to represent various aspects of physical rehabilitation exercises. State-of-the-art NLP algorithms were then developed and compared, including rule-based, machine learning–based algorithms (support vector machine, logistic regression, gradient boosting, and AdaBoost) and large language model (LLM)–based algorithms (ChatGPT [OpenAI]). The study focused on key performance metrics, particularly F1-scores, to evaluate algorithm effectiveness.

Results
The analysis was conducted on a data set comprising 23,724 notes with detailed demographic and clinical characteristics. The rule-based NLP algorithm demonstrated superior performance in most areas, particularly in detecting the “Right Side” location with an F1-score of 0.975, outperforming gradient boosting by 0.063. Gradient boosting excelled in “Lower Extremity” location detection (F1-score: 0.978), surpassing rule-based NLP by 0.023. It also showed notable performance in the “Passive Range of Motion” detection with an F1-score of 0.970, a 0.032 improvement over rule-based NLP. The rule-based algorithm efficiently handled “Duration,” “Sets,” and “Reps” with F1-scores up to 0.65. LLM-based NLP, particularly ChatGPT with few-shot prompts, achieved high recall but generally lower precision and F1-scores. However, it notably excelled in “Backward Plane” motion detection, achieving an F1-score of 0.846, surpassing the rule-based algorithm’s 0.720.

Conclusions
The study successfully developed and evaluated multiple NLP algorithms, revealing the strengths and weaknesses of each in extracting physical rehabilitation exercise information from clinical notes. The detailed ontology and the robust performance of the rule-based and gradient boosting algorithms demonstrate significant potential for enhancing precision rehabilitation. These findings contribute to the ongoing efforts to integrate advanced NLP techniques into health care, moving toward predictive models that can recommend personalized rehabilitation treatments for optimal patient outcomes.
Effect of Spironolactone on Kidney Function in Kidney Transplant Recipients (the SPIREN trial)
Authors: Mortensen Line A. , Jespersen Bente , Helligsoe Anne Sophie L. , Tougaard Birgitte , Cibulskyte-Ninkovic Donata , Egfjord Martin , Boesby Lene , Marcussen Niels , Madsen Kirsten , Jensen Boye L. , Petersen Inge , Bistrup Claus , Thiesson Helle C. 
Published: February 2024

Key Points

Spironolactone is safe for kidney transplant patients.Spironolactone reduces kidney function by an acute effect, whereafter it remains stable.Spironolactone does not affect the progression of interstitial fibrosis in protocol biopsies.

Background
Long-term kidney allograft survival is hampered by progressive interstitial fibrosis and tubular atrophy. The SPIREN trial tested the hypothesis that the mineralocorticoid receptor antagonist spironolactone stabilizes kidney function and attenuates glomerular barrier injury in kidney transplant patients treated with calcineurin inhibitors.

Methods
We conducted a randomized, placebo-controlled, double-blind clinical trial including 188 prevalent kidney transplant patients. Patients were randomized to spironolactone or placebo for 3 years. GFR was measured along with proteinuria and kidney fibrosis. The primary end point was change in measured GFR. Secondary outcomes were 24-hour proteinuria, kidney allograft fibrosis, and cardiovascular events. Measured GFRs, 24-hour proteinuria, and BP were determined yearly. Kidney biopsies were collected at baseline and after 2 years (n=48). Fibrosis was evaluated by quantitative stereology and classified according to Banff.

Results
The groups were comparable at baseline except for slightly older allografts in the spironolactone group. Spironolactone reduced measured GFRs (up to –7.6 [95% confidence interval, −10.9 to −4.3] ml/min compared with placebo) independently of time since transplantation and BP with no effect on the kidney function curve over time and reduced 24-hour proteinuria after 1 year. There was no significant effect of spironolactone on the development of interstitial fibrosis.

Conclusions
Spironolactone added to standard therapy for 3 years in kidney transplant patients did not improve kidney function, long-term proteinuria, or interstitial fibrosis.

Clinical Trial registration number

NCT01602861.
Self-Assessment Regime, Tax Compliance, And Tax Administration: Evidence From Emerging Economy
Authors: Madugba Joseph , Egbide Ben-caleb, , Nonye. D Uzoka, , Vivian I. Oparah , Chinagorom Onuoha, , Mmerenini Godwin, , Andrew Agbiogwu, , James Dokia 
Published: February 2024

Purpose: This study examined the effect of self-assessment regime and tax compliance on tax administration in Nigeria. The specific objective was to find out the effect fiscal governance quality tax-payers knowledge (TKW), filling of tax returns (FTR), financial constraints (FCT), ability to pay tax without being compelled (PAC).
Methodology/approach: The study adopted the survey research design This is because the objective of the study is to systematically obtain information to describe how self-assessment endues tax compliance and tax administration. The population of this study is the 96 conventional Federal Inland Revenue Tax offices and all corporate taxpayers in Nigeria. The study utilized the purposive sampling technique considering responses from our respondents, fifteen conventional federal inland revenue tax offices and twenty-five corporate taxpayers were chosen for the study. One hundred and two respondents out of which forty-five were from conventional Federal Inland revenue tax office and fifty-seven responses from corporate taxpayers. The source of data is primary and five-point Likert scale questionnaires were designed to generate responses from respondents. Out of a total number of 750 questionnaires sent out through Google, only 252 were returned. The study made use of inferential and descriptive statistics to analyze the responses with the aid of SPSS.
Findings: The finding indicated that there is a significant association between tax knowledge and ability to pay tax without being forced and governance quality, but filling of tax return and financial constraint have negative effect on governance quality. The study concluded that the association between self-assessment regime and tax compliance and tax administration in Nigeria is significant and the study recommended that loopholes from where tax revenue is lost should be covered to increase tax revenue in Nigeria.
Practical Implication: The research finding has an effect on tax policy makers and taxpayers in Nigeria
Originality/Value: this study is having modified the existing variables used by previous and introduced new ones as it introduced financial constraint and ability to pay tax as a measure of tax compliance.
The Validity of Computed Tomography Guided Lung Tru- cut Biopsies in Achieving Accurate Tissue Results
Authors: Khashman Basim Mohammed , Mohson Khaleel I , Abdul Qader Omar Abdul Jabbar , Abdul Ghafour Kifah H. 
Published: February 2024

Objective: This study aims to assess the efficacy of CT-guided true-cut biopsy as a less invasive and cost-effective diagnostic technique for peripherally placed lung lesions.

Methods: fourty patients with solitary lung nodule were involved in this study, true cut biopsies under Ct guide was taken then processed for routine H&E staining.

Results: different pathological features can be identified with different pathological features giving primary diagnostic screening for lung cancer

Conclusion: CT guided thoracic lesion biopsy is very efficient, cost-effective and less invasive technique when compared with the thoracic surgery
Unveiling the Mediating Role of the REJ Region: PC1 and Extracellular Matrix Dynamics in ADPKD
Authors: Alrashidi Aljazi Abdullah , Sonbol Hala Salim 
Published: February 2024

Objective: This study aimed to investigate the interactions of PC1 with extracellular matrix proteins (ECM) to gain insights into its role in ADPKD onset. This exploration objective is to unravel the significance of these interactions in both the healthy development of kidneys and the underlying mechanisms of ADPKD, potentially identifying therapeutic targets.
Methods: We cloned and expressed the receptor of the egg jelly (REJ) domain as a maltose-binding protein-fusion protein (PET21-MBP(TEV)-REJ). Subsequently, we utilized this construct in a pulldown assay involving HEK 293 cells. In vitro, pull-down assays were conducted to evaluate the binding of the REJ fusion to various ECM components.
Results: The REJ fusion protein effectively binds to vitronectin, Fibulin-1, and actin filament-associated protein (AFAP) 1. These findings indicate that the REJ region acts as a mediator for the interaction between polycystin-1 and the ECM, shedding light on the functional role of polycystin-1 in both cell-matrix and cell-cell interactions.
Conclusion: The detailed characterization of REJ-ECM interactions offers a valuable foundation for future research aimed at systematically studying the effects of disease-causing mutations within the REJ module of human PC-1.
Accuracy and Feasibility of Real-time Continuous Glucose Monitoring in Critically Ill Patients After Abdominal Surgery and Solid Organ Transplantation
Authors: Voglová Hagerf Barbora , Protus Marek , Nemetova Lenka , Mraz Milos , Kieslichova Eva , Uchytilova Eva , Indrova Veronika , Lelito Jan , Girman Peter , Haluzík Martin , Franekova Janka , Svirlochova Veronika , Klonoff David C. , Kohn Michael A. , Jabor Antonin 
Published: February 2024

OBJECTIVE
Glycemia management in critical care is posing a challenge in frequent measuring and adequate insulin dose adjustment. In recent years, continuous glucose measurement has gained accuracy and reliability in outpatient and inpatient settings. The aim of this study was to assess the feasibility and accuracy of real-time continuous glucose monitoring (CGM) in ICU patients after major abdominal surgery.

RESEARCH DESIGN AND METHODS
We included patients undergoing pancreatic surgery and solid organ transplantation (liver, pancreas, islets of Langerhans, kidney) requiring an ICU stay after surgery. We used a Dexcom G6 sensor, placed in the infraclavicular region, for real-time CGM. Arterial blood glucose measured by the amperometric principle (ABL 800; Radiometer, Copenhagen, Denmark) served as a reference value and for calibration. Blood glucose was also routinely monitored by a StatStrip bedside glucose meter. Sensor accuracy was assessed by mean absolute relative difference (MARD), bias, modified Bland-Altman plot, and surveillance error grid for paired samples of glucose values from CGM and acid-base analyzer (ABL).

RESULTS
We analyzed data from 61 patients and obtained 1,546 paired glucose values from CGM and ABL. Active sensor use was 95.1%. MARD was 9.4%, relative bias was 1.4%, and 92.8% of values fell in zone A, 6.1% fell in zone B, and 1.2% fell in zone C of the surveillance error grid. Median time in range was 78%, with minimum (&lt;1%) time spent in hypoglycemia. StatStrip glucose meter MARD compared with ABL was 5.8%.

CONCLUSIONS
Our study shows clinically applicable accuracy and reliability of Dexcom G6 CGM in postoperative ICU patients and a feasible alternative sensor placement site.