bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine Learning-Driven Advancements in Liposomal Formulations for Targeted Drug Delivery: A Narrative Literature Review
Authors: Hoseini Benyamin , Jaafari Mahmoud Reza , Golabpour Amin , Rahmatinejad Zahra , Karimi Maryam , Eslami Saeid 
Published: June 2024

Abstract:
Nanoliposomal formulations, utilizing lipid bilayers to encapsulate therapeutic agents,
hold promise for targeted drug delivery. Recent studies have explored the application of machine
learning (ML) techniques in this field. This study aims to elucidate the motivations behind integrating
ML into liposomal formulations, providing a nuanced understanding of its applications and
highlighting potential advantages. The review begins with an overview of liposomal formulations
and their role in targeted drug delivery. It then systematically progresses through current research
on ML in this area, discussing the principles guiding ML adaptation for liposomal preparation and
characterization. Additionally, the review proposes a conceptual model for effective ML incorporation.
The review explores popular ML techniques, including ensemble learning, decision trees, instance-
based learning, and neural networks. It discusses feature extraction and selection, emphasizing
the influence of dataset nature and ML method choice on technique relevance. The review underscores
the importance of supervised learning models for structured liposomal formulations,
where labeled data is essential. It acknowledges the merits of K-fold cross-validation but notes the
prevalent use of single train/test splits in liposomal formulation studies. This practice facilitates
the visualization of results through 3D plots for practical interpretation. While highlighting the
mean absolute error as a crucial metric, the review emphasizes consistency between predicted and
actual values. It clearly demonstrates ML techniques' effectiveness in optimizing critical formulation
parameters such as encapsulation efficiency, particle size, drug loading efficiency, polydispersity
index, and liposomal flux. In conclusion, the review navigates the nuances of various ML algorithms,
illustrating ML's role as a decision support system for liposomal formulation development.
It proposes a structured framework involving experimentation, physicochemical analysis,
and iterative ML model refinement through human-centered evaluation, guiding future studies.
Emphasizing meticulous experimentation, interdisciplinary collaboration, and continuous validation,
the review advocates seamless ML integration into liposomal drug delivery research for robust
advancements. Future endeavors are encouraged to uphold these principles.
HucMSCs-derived Exosomes Protect Against 6-hydroxydopamine-induced Parkinson’s Disease in Rats by Inhibiting Caspase-3 Expression and
Suppressing Apoptosis
Authors: Chen Hong-Xu , Xu Hong-Jun , Zhang Wang , Luo Zi-Yu , Zhang Zhong-Xia , Shi Hao-Han , Dong Yu-Chang , Xue Zhan-Jun , Ben Ying , An Sheng-Jun 
Published: June 2024

Objective:
Parkinson’s disease (PD) is a progressive neurodegenerative disorder with
symptoms including tremor and bradykinesia, while traditional dopamine replacement therapy
and hypothalamic deep brain stimulation can temporarily relieve patients’ symptoms, they cannot
cure the disease. Hence, discovering new methods is crucial to designing more effective therapeutic
approaches to address the condition. In our previous study, we found that exosomes (Exos) derived
from human umbilical cord mesenchymal stem cells (hucMSCs) repaired a PD model by inducing
dopaminergic neuron autophagy and inhibiting microglia. However, it is not clear whether
its therapeutic effect is related to inhibiting apoptosis by inhibiting caspase-3 expression.

Methods:
Three intervention schemes were used concerning previous literature, and the dosage of
each scheme is the same, with different dosing intervals and treatment courses and to compare the
aspects of behavior, histomorphology, and biochemical indexes. To predict and determine target
gene enrichment, high-throughput sequencing and miRNA expression profiling of exosomes, GO
and KEGG analysis, and Western blot were used.

Results:
Exos labeled with PKH67 were found to reach the substantia nigra through the blood-
-brain barrier and existed in the liver and spleen. 6-hydroxydopamine (6-OHDA) induced PD rats
were treated with Exos every two days for one month, which alleviated the asymmetric rotation induced
by morphine, reduced the loss of dopaminergic neurons in the substantia nigra, and increased
dopamine levels in the striatum. The effect became more significant as the treatment time
was extended to two months. These results suggest that hucMSCs-Exos can inhibit the 6-OHDA-
induced neuron damage in PD rats, and its neuroprotective effects may be mediated by inhibiting
cell apoptosis. Through high-throughput sequencing of miRNA, potential targets for Exos to
inhibit apoptosis may be BAD, IKBKB, TRAF2, BCL2, and CYCS.

Conclusion:
The above results indicate that hucMSCs-Exos can inhibit 6-OHDA-induced damage
in PD rats, and its neuroprotective effect may be mediated by inhibiting cell apoptosis.
The Relationship between the Clinical Course of SARS-CoV-2 Infections and Expression of Bruton's Tyrosine Kinase
Authors: Rezaei Mitra , Babamahmoodi Abdolreza , Mirahmadi Alireza , Bineshfar Niloufar , Mahmoudi Shima , Ghadimi Somayeh , Valizadeh Melika , Malakouti Tannaz , Taheri Fatemeh Talebian , Mohammadpour Hadiseh , Azadani Farinaz Nasr , Ziai Seyed Ali , Poorhosseini Seyed Mohammad , Marjani Majid 
Published: June 2024

Introduction:
Bruton’s Tyrosine Kinase (BTK), an important element for the pro-duction of several inflammatory cytokines, may play a role in the pathogenesis of COVID-19. This study aimed to assess BTK gene expression levels in COVID-19 cases based on disease severity and outcome.

Methods:
In this study, 33 hospitalized patients with COVID-19 were recruited and divided into two groups based on the severity of the disease: "mild to moderate" and "severe to critical". A blood sample was taken from each patient, peripheral blood mononuclear cells (PBMCs) were extracted, and BTK gene expression was measured. The level of BTK gene expression was compared based on the demographic data, laboratory results, and the severity and outcome of the disease.

Results:
Among 33 patients, 22 (66.7%) were male. Nearly half of the cases had at least one underlying disease. According to the severity of the disease, 12 patients were in the "mild to moderate" group, and 21 were in the "severe to critical" group; eight (24.2%) eventually died. Age, weight, and BMI had no significant relationship with BTK expression. BTK expression was significantly lower in "severe to critical" and ICU-admitted cases and in subjects with low O2 saturation. There was no significant difference in BTK expression between cured and dead patients (p=0.117).

Conclusion:
BTK gene expression in PBMCs had an inverse relationship with the severity of the disease of COVID-19. However, no correlation between BTK expression and disease outcome was observed.
Stylosin Exerts Cytotoxic and Apoptogenic Effects in Human Malignant
Glioblastoma Line and Hepatocellular Carcinoma Cells: The Role of
Reactive Oxygen Species
Authors: Alavi Mohaddeseh Sadat , Rashidi Roghayeh , Mobasheri Leila , Sheykhi Salmabad Nafiseh , Kazemi Seyedeh Safa , Mirzavi Farshad , Hosseini Azar 
Published: June 2024

Objective::
Cancer is one of the major public health challenges globally and the second
cause of death in developed countries. Studies have shown that natural products can be effective
in treating cancer. The present study was conducted on the cytotoxicity and apoptogenic effects
of stylosin on the HepG2 and U87 cell lines.

Methods and Materials::
First, the cytotoxicity effect of stylosin was investigated using the MTT
method. Also, the production of reactive oxygen species was measured. The amount of cell
apoptosis was determined by the Sub G1 Peak method. Finally, to investigate the cellular and
molecular mechanisms involved in stylosin toxicity, the expression of P53, BAX, Bcl-2, Caspase
3, Caspase 9, and p53 genes were evaluated by the RT-PCR method.

Results::
Stylosin causes cytotoxicity in HepG2 and U87 cells in a time and concentrationdependent
pattern. It also significantly increases ROS production and stimulates apoptosis. It
induced a substantial enhancement in the expression of BAX, caspase3, and Caspase9 genes in
HepG2 while decreasing Bcl-2 production and up-regulation of Caspase 3, Caspase 9, and p53 in
U87 cells.

Conclusion::
It is concluded that Stylosin can probably inhibit the proliferation of the cancer cell
line by affecting the expression of genes involved in apoptosis and the production of ROS.
A Universal Digital Stress Management Intervention for Employees: Randomized Controlled Trial with Health-Economic Evaluation
Authors: Freund Johanna , Smit Filip , Lehr Dirk , Zarski Anna-Carlotta , Berking Matthias , Riper Heleen , Funk Burkhardt , Ebert David Daniel , Buntrock Claudia 
Published: June 2024

Background
Stress is highly prevalent and known to be a risk factor for a wide range of physical and mental disorders. The effectiveness of digital stress management interventions has been confirmed; however, research on its economic merits is still limited.

Objective
This study aims to assess the cost-effectiveness, cost-utility, and cost-benefit of a universal digital stress management intervention for employees compared with a waitlist control condition within a time horizon of 6 months.

Methods
Recruitment was directed at the German working population. A sample of 396 employees was randomly assigned to the intervention group (n=198) or the waitlist control condition (WLC) group (n=198). The digital stress management intervention included 7 sessions plus 1 booster session, which was offered without therapeutic guidance. Health service use, patient and family expenditures, and productivity losses were self-assessed and used for costing from a societal and an employer’s perspective. Costs were related to symptom-free status (PSS-10 [Perceived Stress Scale] score 2 SDs below the study population baseline mean) and quality-adjusted life years (QALYs) gained. The sampling error was handled using nonparametric bootstrapping.

Results
From a societal perspective, the digital intervention was likely to be dominant compared with WLC, with a 56% probability of being cost-effective at a willingness-to-pay (WTP) of €0 per symptom-free person gained. At the same WTP threshold, the digital intervention had a probability of 55% being cost-effective per QALY gained relative to the WLC. This probability increased to 80% at a societal WTP of €20,000 per QALY gained. Taking the employer’s perspective, the digital intervention showed a probability of a positive return on investment of 78%.

Conclusions
Digital preventive stress management for employees appears to be cost-effective societally and provides a favorable return on investment for employers.

Trial Registration
German Clinical Trials Register DRKS00005699; https://drks.de/search/en/trial/DRKS00005699
Examining the Relationships Between Indoor Environmental Quality Parameters Pertaining to Light, Noise, Temperature, and Humidity and the Behavioral and Psychological Symptoms of People Living With Dementia: Scoping Review
Authors: Au-Yeung Wan-Tai M , Miller Lyndsey , Wu Chao-Yi , Beattie Zachary , Nunnerley Michael , Hanna Remonda , Gothard Sarah , Wild Katherine , Kaye Jeffrey 
Published: June 2024

Background
A common challenge for individuals caring for people with Alzheimer disease and related dementias is managing the behavioral and psychological symptoms of dementia (BPSD). Effective management of BPSD will increase the quality of life of people living with dementia, lessen caregivers’ burden, and lower health care cost.

Objective
In this review, we seek to (1) examine how indoor environmental quality parameters pertaining to light, noise, temperature, and humidity are associated with BPSD and how controlling these parameters can help manage these symptoms and (2) identify the current state of knowledge in this area, current gaps in the research, and potential future directions.

Methods
Searches were conducted in the CINAHL, Embase, MEDLINE, and PsycINFO databases for papers published from January 2007 to February 2024. We searched for studies examining the relationship between indoor environmental quality parameters pertaining to light, noise, temperature, and humidity and BPSD.

Results
A total of 3123 papers were identified in the original search in October 2020. After an additional 2 searches and screening, 38 (0.69%) of the 5476 papers were included. Among the included papers, light was the most studied environmental factor (34/38, 89%), while there were fewer studies (from 5/38, 13% to 11/38, 29%) examining the relationships between other environmental factors and BPSD. Of the 38 studies, 8 (21%) examined multiple indoor environmental quality parameters. Subjective data were the only source of environmental assessments in 6 (16%) of the 38 studies. The findings regarding the relationship between agitation and light therapy are conflicted, while the studies that examined the relationship between BPSD and temperature or humidity are all observational. The results suggest that when the environmental factors are deemed overstimulating or understimulating for an individual with dementia, the behavioral symptoms tend to be exacerbated.

Conclusions
The findings of this scoping review may inform the design of long-term care units and older adult housing to support aging in place. More research is still needed to better understand the relationship between indoor environmental quality parameters and BPSD, and there is a need for more objective measurements of both the indoor environmental quality parameters and behavioral symptoms. One future direction is to incorporate objective sensing and advanced computational methods in real-time assessments to initiate just-in-time environmental interventions. Better management of BPSD will benefit patients, caregivers, and the health care system.
Enhanced therapy for coronary artery disease and diabetes mellitus: impact on biomarkers and clinical outcomes
Authors: Fedorov S.V. , Didushko O.M. , Nyshchuk-Oliinyk N.B. , Pozur N.Z. , Bielinskyi M.V. , Herashchenko A.S. 
Published: June 2024

Background. Cardiovascular diseases like coronary artery disease (CAD) are a major global health issue, causing millions of deaths each year. Type 2 diabetes mellitus (T2DM) worsens outcomes for those with CAD. Common risk factors suggest potential synergistic treatment approaches, including the use of quercetin, a natural flavonoid. The purpose was to examine the clinical efficacy and safety of empagliflozin and quercetin in the treatment of coronary artery disease and type 2 diabetes mellitus comorbidity in the light of their impact on parameters of inflammation. Materials and methods. A total of 128 patients diagnosed with both stable CAD and T2DM were enrolled in the study between January and December 2023. Participants were categorized into three groups. Group 1 (controls): 40 patients receiving the standard treatment protocol for CAD and T2DM. Group 2: 46 patients received standard therapy in addition to empagliflozin (10 mg daily). Group 3: 42 patients received standard therapy in addition to empagliflozin (10 mg daily) and quercetin (80 mg three times a day). Results. The results showed that age and gender were similar between the groups, indicating a balanced distribution. The study then evaluated the effects of treatment on various parameters. The baseline body mass index (BMI), glucose, glycated hemoglobin (HbA1c), soluble suppression of tumorigenicity 2 (sST2), Toll-like receptor 2 (TLR2) and TLR4 levels were comparable across all groups. After treatment, significant reductions were observed in BMI, fasting glucose, HbA1c, sST2, and TLR2/TLR4 in all groups. The most significant improvements were seen in the group that received both empagliflozin and quercetin. The findings highlight the potential benefits of these interventions in patients with coronary heart disease and type 2 diabetes mellitus. Conclusions. The addition of empagliflozin and quercetin to standard therapy appears to offer significant benefits in managing BMI, glycemic control, and inflammatory markers in patients with CAD and T2DM. The combined treatment regimen has potential to address the complex interplay of metabolic and inflammatory processes in high-risk patients. The proposed combination also showed efficacy in reducing the myocardial stress, which is shown by a decrease in serum sST2.
The Position of Ijbar Rights in Perspective Islamic Law and Human Rights
Authors: Munir Misbachul , Zumrotun Siti 
Published: June 2024

This article aims to illustrate the concept of ijbar according to Islamic religious law based on the opinion of jurists about the right to force a girl (ijbar right) to marry owned by her guardian even without her consent because a guardian is considered to be the one who knows best about what is best because women are considered not proficient in formulating things that are best for her, Therefore, consent is not a priority that ultimately monopolizes women's interests and has the potential to cause violence against women, therefore this article tries to describe ijbar rights according to the perspective of Islamic Law and Human Rights.
Comparison of Biochemical Parameters in Vaccinated and Non-vaccinated SARS-COV-2 Patients in Erbil-City
Authors: Ahmed Hardi S. , Nanakali Nadir M.Q. , Ali Khabat A. 
Published: June 2024

COVID-19 is one of the major pandemic caused by SARS-CoV-2. Vaccination is one of the methods used that reduce the spread of an infectious disease. Consequently, we aimed to measure the levels of some liver parameters (ALT, AST, ALP, TSB, LDH and Albumin), as well as bone markers (Ca, P, PTH and TSH) as marker for the severity of the disease in Non-vaccinated and Vaccinated SARS-COV-2 patients. Between November 2021 and May 2022, 130 sample of both genders (healthy and infected with COVID-19) were obtained, and divided into three major groups: healthy individuals (50), vaccinated (30) and non-vaccinated (50) group" (ages; 20-65). Our findings showed that serum ALT, ALP, LDH, significantly elevated (p < 0.01), and despite comparing patients who were not vaccinated to those who were, serum albumin considerably dropped. Moreover, serum AST and TSB moderately elevated in unvaccinated group in comparison to unvaccinated patients. Regarding bone markers, Ca and P, slightly decreased in non-vaccinated and vaccinated patients compare to healthy control group. Whereas the serum PTH and TSH significantly less in both patient groups than in control. “The optimal cut-off values for liver parameters and bone markers were determined by ROC Curve Analysis. In conclusion, vaccine plays major role in minimizing liver biomarkers in COVID-19 patients. Moreover, low concentrations of serum bone markers were associated with both vaccinated and non-vaccinated COVID-19 patients. Therefore, the bone health status of COVID patients and liver markers are helpful for the diagnosis and monitoring of disease severity in COVID‐19 patient.
Comparative pharmacokinetics of phenylbutazone in healthy young-adult and geriatric horses
Authors: Zaghloul Iman Y. , Bedenice Daniela , Ceresia Michelle L. , Jones Pilar Hermida , Sanchez-Londono Alfredo , Lobo Mitchell N. , Böhlke Mark , Paradis Mary Rose 
Published: June 2024

Abstract

OBJECTIVE
To evaluate the effects of aging on phenylbutazone (PBZ) disposition in older horses (≥ 25 years old) compared to young adults (4 to 10 years old) by characterizing the pharmacokinetic profile of PBZ and its active metabolite, oxyphenbutazone (OPBZ), following a 2.2-mg/kg dose, IV. We hypothesized that the disposition of PBZ will be affected by age.

ANIMALS
16 healthy horses (8 young adults aged 4 to 10 years and 8 geriatric horses ≥ 25 years old).

METHODS
Horses were administered a single 2.2-mg/kg PBZ dose, IV. Plasma samples were collected at designated time points and frozen at –80 °C until assayed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analyses were performed using Phoenix WinNonlin, version 8.0 (Certara). Both clinical and pharmacokinetic data were compared between age groups using independent samples t tests, with P < .05 considered significant.

RESULTS
Baseline characteristics did not differ between groups, with the exception of age, weight, and plasma total solids. Plasma concentrations of PBZ were best described by a two-compartment model. The maximum plasma concentration of OPBZ was reached at 5 hours for both age groups, and the metabolite-to-parent-drug area-under-the-curve ratios were approximately 20% for both groups. None of the pharmacokinetic parameters of PBZ or its metabolite, OPBZ, differed significantly between age groups.

CLINICAL RELEVANCE
The hypothesis was rejected as there was no significant difference in PBZ disposition in young-adult horses compared to geriatric horses. Our data do not support the need for dose adjustments of PBZ in clinically healthy geriatric horses.
Investigation of the disinfection efficiency of commercial hydrogen peroxide, chlorine dioxide, and chlorine disinfectant on different surfaces
Authors: Tao Chunai , Tang Xiaolan , Gan Yongxin , Qin Yun , Yang Shuting , Huang Fengshun 
Published: June 2024

Abstract

OBJECTIVE
The disinfection efficiency of disinfectants differs in specific conditions. This study aimed to investigate the disinfection efficiency of commercial hydrogen peroxide, chlorine dioxide, and chlorine disinfectant on real field surfaces and provide data for precise disinfection.

METHODS
Simulated field disinfection and field disinfection methods were conducted to quantitatively evaluate the disinfection efficiency of hydrogen peroxide, chlorine dioxide, and sodium dichloroisocyanurate. The log10 reduction of biological indicators, Escherichia coli (ATCC 8099) and Staphylococcus aureus (ATCC 6538), was calculated. Next, the reduction in natural bacteria on the surfaces of a food production and processing workshop and a biosafety laboratory was determined.

RESULTS
The 3 commercial disinfectants evaluated were effective against E coli and S aureus, with a reduction of more than 3.00 log10 colony-forming units/mL tested for an exposure time of 15 minutes with 3.5% hydrogen peroxide, 100 mg/L chlorine dioxide, and 250 mg/L sodium dichloroisocyanurate. The natural load in the food production and processing workshop decreased by more than 90% using 10.5% hydrogen peroxide with an exposure time of 30 minutes. The same disinfection level in the biosafety level 2 laboratory was achieved by 500 mg/L chlorine dioxide at an exposure time of 60 minutes and 450 mg/L sodium dichloroisocyanurate at 60 minutes.

CLINICAL RELEVANCE
This study provides a reference for precise disinfection of surfaces in the food industry and biosafety laboratories.