bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of Drugs to Drowning in Scotland from 1996 to 2020
Authors: Corkery John Martin , Martinotti Giovanni , Schifano Fabrizio 
Published: August 2022

Objective:
Psychoactive substance use (including alcohol) can affect risk perception, leading
to accidents and deaths. There is little detailed or up-to-date information on the role of drugs in drownings
in the United Kingdom (UK). This Scottish case-study aimed to fill this knowledge gap

Methods:
Anonymised data for individual drug-poisoning-related drowning registered from 1996 to
2020 were provided by the National Records of Scotland. Statistical analyses were performed for
socio-demographics, ICD coding, cause of death, and substances implicated.

Results:
It has been reported that death registrations increased from 7 in 2017 to over 20 during
2019-20. These deaths (n=160) accounted for <1% of all drug-related poisoning deaths; this proportion
rose to record levels (c.1.5%) during 2019-20. Most deaths (69%) involved males. The mean
age was 39.8 (range 16-81, SD 15.0) years. The main drug classes implicated were: opiates/opioids
(41%), benzodiazepines (31%), stimulants (19%), and antidepressants (14%). Moreover, 57% of
benzodiazepines were ‘designer’ drugs.

Conclusions:
Scottish drownings associated with drug consumption are increasing rapidly. It has
been observed that central nervous system depressant drugs (e.g., opioids, benzodiazepines, alcohol)
are often involved in drowning. ‘Designer’ benzodiazepines are a principal factor in increasing
Scottish drug-related poisoning deaths; they may be partially responsible for increasing numbers of
related drownings. Evidence-based strategies to further reduce the number of preventable drownings
should include reference to the dangers of drugs.
Mitochondrial Medicine: A Promising Therapeutic Option Against Various Neurodegenerative Disorders
Authors: Almikhlafi Mohannad A. , Karami Mohammed M. , Jana Ankit , Alqurashi Thamer M. , Majrashi Mohammed , Alghamdi Badrah S. , Ashraf Ghulam Md. 
Published: August 2022

Abstract:Abnormal mitochondrial morphology and metabolic dysfunction have been observed in many neurodegenerative disorders (NDDs). Mitochondrial dysfunction can be caused by aberrant mitochondrial DNA, mutant nuclear proteins that interact with mitochondria directly or indirectly, or for unknown reasons. Since mitochondria play a significant role in neurodegeneration, mitochondriatargeted therapies represent a prosperous direction for the development of novel drug compounds that can be used to treat NDDs. This review gives a brief description of how mitochondrial abnormalities lead to various NDDs such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. We further explore the promising therapeutic effectiveness of mitochondria- directed antioxidants, MitoQ, MitoVitE, MitoPBN, and dimebon. We have also discussed the possibility of mitochondrial gene therapy as a therapeutic option for these NDDs.
A Network Pharmacology-based Mechanism of the Traditional Chinese
Medicine Formula Li Kun Zhi Ji acting on Colon Cancer
Authors: Liu Guoyan , Liu Yanling , Duan Linshan , Li Long , Jin Yanling , Hong Yuling , Wang Dan 
Published: August 2022

Backgrounds:
Li Kun Zhi Ji (LKZJ) is a traditional Chinese medicine formula that effectively improves the immune system. However, the mechanism of its action against cancer remains unknown. Our study aimed to determine whether LKZJ inhibits the growth of the human colon cancer cell line HCT-116, and we performed in vitro experiments to further explore the associated molecular mechanisms.

Objective:
We explored the antitumor function and the mechanism of LKZJ against human colon cancer cells.

Methods:
We selected the effective components of LKZJ. Then, the potential targets of these components were obtained against colon cancer, and an “LKZJ-targets-colon cancer” network was constructed. After that, a CCK-8 assay was used to assess cell viability. Next, apoptosis was analyzed with PI/Annexin V assay using flow cytometry. Finally, western blotting was carried out to determine the expression levels of the protein.

Results:
We obtained 36 effective LKZJ components and identified 225 candidate targets acting on colon cancer. We demonstrated that the cell viability of HCT-116 cells had significantly decreased after treatment of LKZJ. The suppression of HCT-116 proliferation by LKZJ through inducing apoptosis was determined using Flow cytometry. In addition, mitochondria-associated apoptosis was stimulated, and the down-regulation of Bcl-2 and up-regulation of Bax and Bad were observed. LKZJ also attenuated the PI3K/Akt signaling pathway through western blotting.

Conclusion:
Our study revealed that LKZJ induced HCT-116 cell line apoptosis through the PI3K/Akt apoptotic pathway. Our results indicated that LKZJ could be a possible therapeutic agent against human colon cancer.
Echocardiography Parameters in Behcet’s Disease, A Comparative Study
Authors: Mirfeizi Zahra , Poorzand Hoorak , Manzari Reza Salehi , Abbasi Shaye Zahra 
Published: August 2022

Objective:
Behçet's disease (BD) is a chronic inflammatory disease with multiple organ involvements. Although cardiac involvement is not common, it can increase patient morbidity and mortality and decrease life quality. In the present study, echocardiographic abnormalities in BD with no cardiac symptoms were investigated.

Methods:
This cross-sectional descriptive-analytic study was performed on patients referred to Imam Reza Hospital in Mashhad from 2015 to 2018. The participants were divided into control and BD groups. Patients with BD were diagnosed based on ISG criteria. All participants underwent transthoracic echocardiography. Echocardiographic parameters were compared between BD and control groups.

Results:
In this study, the severity of aortic (AR), mitral (MR), and tricuspid valve regurgitation (TR) was higher in BD than in the control group, while only TR severity showed a statistically sig-nificant difference (p-value < 0.001). Systolic Pulmonary Artery Pressure (sPAP) was significantly higher in BD compared to the control group (24.6 mmHg versus 22.81 mmHg, respectively) (p-value = 0.019).

Conclusion:
It seems echocardiography is valuable in evaluating a cardiac function, even in asymp-tomatic patients. Cases with moderate mitral and aortic regurgitation were only observed in BD. Long-term follow-up is suggested, and further studies are required.
iTRAQ-based Proteomics Analysis of ADTM for Preventing the
Development of Nitroglycerin-induced Tolerance
Authors: Shan Luchen , Hu Huihui , Wu Jia , Guo Baojian , Wang Yuqiang 
Published: August 2022

Background:
Long-term nitroglycerin (NTG) therapy causes tolerance, which limits its clinical
application. Previous studies have reported a novel Danshensu/tetramethylpyrazine derivative ADTM,
which displays strong cardioprotective effects. However, the effect of ADTM is not known in the NTGinduced
tolerance model. In this study, we aimed to evaluate the potential improvement and underlying
mechanism of ADTM for preventing the development of NTG-induced tolerance in in vivo and in vitro
experiments.

Methods:
Firstly, the effect of ADTM was determined on NTG-induced tolerance using isolated thoracic
aortic rings obtained from rats (50 μM for 45 min). After intragastric administration of ADTM (30 mg/kg,
twice a day) for 7 days, NTG solution (10 mg/kg) was subcutaneously injected into male Sprague-Dawley
(SD) rats once a day for 7 consecutive days. The systolic arterial pressure (SAP), diastolic arterial pressure
(DAP), and mean arterial pressure (MAP) were recorded using the PowerLab system. The iTRAQ-based
proteomics analysis was used to clarify the underlying mechanism of ADTM in NTG-induced tolerance.

Results:
ADTM markedly enhanced relaxation sensitivity and vasodilator responses to NTG tolerance in
the isolated rat thoracic aorta, and this effect was independent of the vascular endothelium. ADTM prevented
the development of NTG-induced tolerance in rats by improving hemodynamic parameters, such as
SAP, DAP, and MAP. The iTRAQ-based proteomic analysis suggests that ADTM prevention of NTGinduced
tolerance may be related to the regulation of ribosomal metabolism and tight junctions.

Conclusion:
These results indicate that ADTM has therapeutic potential for NTG-induced tolerance, and is
worthy of further studies.
The Prognostic and Drug-targeting Value of Lymphoid Enhancer-binding
Factor-1 in Hepatocellular Carcinoma
Authors: Guo Ruixiang , Dai Huiru , Liu Fuweijian , Liu Minling , Li Xueying , Li Tingwei , Liao Jiehao , Chen Zhe-Sheng , Liu Yuchen , Fang Shuo 
Published: August 2022

Background:
Lymphoid Enhancer-Binding Factor-1 (LEF1) was previously reported to
contribute to a variety of malignancies, including Hepatocellular Carcinoma (HCC). However, its
role in HCC is poorly understood.

Objective:
To explore the role of LEF1 in HCC, including its prognostic and drug-targeting value.

Methods:
The LEF1 expression and patient characteristics were investigated. The associations
between clinical characteristics and LEF1 were analyzed using both univariate and multivariate
logistic regression. Cox regression and Kaplan-Meier curves were used to explore the clinicopathological
factors related to overall survival in patients with HCC. A nomogram to predict the
survival rate was constructed and validated. The Kyoto Encyclopedia of Genes and Genomes database
(KEGG) was used to explore the function of LEF1. Gene Set Enrichment Analysis (GSEA)
was also performed using The Cancer Genome Atlas dataset. Furthermore, compounds that may
have the potential to be targeted drugs in the treatment of LEF1-overexpressing HCC were identified
using the Comparative Toxicogenomics Database (CTD), patents about these drugs in HCC
were also reviewed through Worldwide Espacenet® and Patentscope®.

Results:
Increased expression of LEF1 was significantly associated with high histological grade of
HCC (odds ratio (OR) = 2.521 for grade (G) 2 vs. G1, OR = 2.550 for G3 vs. G1, OR = 7.081 for
G4 vs. G1, all P < 0.05). A Kaplan–Meier survival curve showed that HCC patients with LEF1
overexpression had a poor prognosis compared with those with normal LEF1 expression (P =
0.025). Multivariate Cox regression analysis revealed that LEF1 is an independent prognostic factor
for the overall survival of patients with HCC (Hazard Ratio (HR) = 1.095; P = 0.04). The constructed
nomogram to predict the survival rate produced a statistically significant prediction (area
under the curve (AUC) = 86.68). In addition, Gene Ontology (GO) and KEGG analysis of genes
co-expressed with the protein showed that LEF1 was associated with transcriptional regulation.
GSEA suggested that the cell cycle, the WNT signaling pathway, and the NOTCH signaling
pathway may be the key pathways regulated by LEF1 in HCC. Furthermore, the Comparative
Toxicogenomics Database (CTD) identified nine compounds that may have the potential to be
targeted drugs in the treatment of LEF1-overexpressing HCC. Patent reviews suggested that these
drugs may show some efficacy in HCC, but whether these drugs interact with LEF1 and improve
the prognosis for patients with HCC remains to be explored.

Conclusion:
LEF1 is a latent prognostic molecular biomarker of HCC. The cell cycle, and WNT
and NOTCH signaling pathways are regulated by LEF1 in HCC. LEF1 could be a potential drug
target for HCC.
Induced Depressive Disorder Following the First Dose of COVID-19
Vaccine
Authors: Rammouz Ismail , Doufik Jalal , Aalouane Rachid , Boujraf Saïd 
Published: August 2022

Introduction:
Several COVID-19 vaccines have been implemented. However, some side
effects of the vaccine have been reported, which are sometimes very harmful. Reported cases and data
are still very limited regarding the psychiatric side effects of the COVID-19 vaccine. To our
knowledge, only one case has been reported. In this paper, we report the case of a patient who presented
an acute depressive episode 24 hours after receiving his first dose of the BNT162b2mRNA vaccine.

Case Report:
The case was a 26-year-old man with a history of Down syndrome with moderately
good autonomy for daily routine tasks. The patient, who presented hypothyroidism at 10 years old and
schizophrenia at 15 years old, was doing well before the vaccination and received his first dose of the
BNT162b2mRNA vaccine. Twenty-four hours later, he presented depressive symptoms that resolved
spontaneously after one week. Then, fifteen days later, the symptoms reappeared, and the episode lasted
for 5 weeks. The patient received 10 mg/day of escitalopram besides his usual treatment. The
depressive symptoms improved considerably by the second day of treatment.

Discussion:
The presented case illustrated significant diagnostic challenges, especially when taking
into account the sequential relationship between the COVID-19 vaccine and the occurrence of depressive
symptoms. A single case of depression has been reported after the administration of the COVID-19 vaccine.
Scientific evidence suggests the important role of the immune system in the pathophysiology of
various psychiatric disorders, including depression.

Conclusion:
Health professionals must take into consideration the potential psychiatric side effects
even being rare so far, especially in vulnerable subjects. Further studies are required to establish the
causal effects of depressive symptoms occurring during the weeks following the COVID-19 vaccine
bolus injection.
Plants and their Bioactive Compounds as a Possible Treatment for Traumatic Brain Injury-Induced Multi-Organ Dysfunction Syndrome
Authors: Thakur Manisha , Vasudeva Neeru , Sharma Sunil , Datusalia Ashok Kumar 
Published: August 2022

Abstract:Traumatic brain injury is an outcome of external forces' physical or mechanical impact on the brain. Thus, the silent epidemic has complex pathophysiology affecting the brain along with extracranial or systemic complications in more than one organ system, including the heart, lungs, liver, kidney, gastrointestinal and endocrine system which is referred to as Multi-Organ Dysfunction Syndrome. It is driven by three interconnected mechanisms, such as systemic hyperinflammation, paroxysmal sympathetic hyperactivity, and immunosuppression-induced sepsis. These multifaceted pathologies accelerate the risk of mortality in clinical settings by interfering with the functions of distant organs through hypertension, cardiac arrhythmias, acute lung injury, neurogenic pulmonary edema, reduced gastrointestinal motility, Cushing ulcers, acute liver failure, acute kidney injury, coagulopathy, endocrine dysfunction, and many other impairments. The pharmaceutical treatment approach for this is highly specific in its mode of action and linked to various side effects, including hallucinations, seizures, anaphylaxis, teeth, bone staining, etc. Therefore, alternative natural medicine treatments are widely accepted due to their broad complementary or synergistic effects on the physiological system with minor side effects. This review is a compilation of the possible mechanisms behind the occurrence of multiorgan dysfunction and reported medicinal plants with organ protective activity that not yet been explored against traumatic brain injury and thereby highlighting the marked possibilities of their effectiveness in the management of multiorgan dysfunction. As a result, we attempted to respond to the hypothesis against using medicinal plants to treat neurodegenerative diseases.
Acute Peripheral Facial Nerve Palsy in Children and Adolescents:
Clinical Aspects and Treatment Modalities
Authors: Jančić Jasna , Zeković Janko , Ćetković Mila , Nikolić Blažo , Ivančević Nikola , Vučević Danijela , Nešić Zorica , Milovanović Srđan , Radenković Miroslav , Samardžić Janko 
Published: August 2022

Background:
Peripheral facial nerve palsy is a relatively frequent, rather idiopathic, and
isolated nonprogressive disorder with a tendency toward spontaneous recovery in children. It is primarily
characterized by unilateral paresis or paralysis of the mimic musculature, affecting verbal
communication, social interactions, and quality of life.

Objective:
This study aimed to evaluate the clinical aspects and efficacy of different therapeutic modalities
in the population of children and adolescents with acute peripheral facial nerve palsy, the quality
and recovery rate in comparison to different therapy modalities and etiological factors as well as to
determine parameters of recovery according to the age of patients.

Methods:
The retrospective study included children and adolescents (n=129) with an acute onset of
peripheral facial nerve palsy, diagnosed and treated in the Clinic of Neurology and Psychiatry for
Children and Youth in Belgrade (2000-2018). The mean age of the patients was 11.53 years
(SD±4.41). Gender distribution was 56.6% female and 43.4% male patients.

Results:
There were 118 (91.5%) patients with partial and 11 (8.5%) patients with complete paralysis.
Left-sided palsy occurred in 67 (51.9%) patients, right-sided in 58 (45.0%), while there were 4 (3.1%)
bilateral paralyses. The most common etiological factor was idiopathic (Bell’s palsy), i.e., 74 (57.4%)
patients, followed by middle ear infections, i.e., 16 (12.4%). Regardless of etiology, age, and therapy
protocols, there was a significant recovery in most of the patients (p<0.001), without significant differences
in recovery rate. Comparison of inpatient and outpatient populations showed significant differences
regarding the number of relapses, the severity of clinical presentation, and the recovery rate in
relation to etiology.

Conclusion:
Bell’s palsy is shown to be the most common cause of peripheral facial nerve palsy in
children and adolescents, regardless of gender. It is followed by mid-ear infections, respiratory infections,
and exposure to cold. Most children and adolescents recovered three weeks after initial presentation,
regardless of etiology, age, and therapy.
Development and Characterization of Novel Chronic Eosinophilic Inflammation-
Mediated Murine Model of Malignant Pancreatitis
Authors: Kandikattu Hemanth Kumar , Venkateshaiah Sathisha Upparahalli , Yadavalli Chandra Sekhar , Oruganti Lokanatha , Mishra Anil 
Published: August 2022

Aims:
Develop a novel murine models of malignant pancreatitis.

Background:
Although patients with chronic pancreatitis are at a greater risk of developing pancreatic
cancer, there is no definitive mouse model that currently develops chronic pancreatitis-induced pancreatic
cancer.

Objective:
Characterization of eosinophilic inflammation-mediated malignant pancreatitis in novel murine
model.

Methods:
We developed a murine model of chronic eosinophilic inflammation associated with pancreatitis
that also shows characteristic features of pancreatic malignancy. The mouse received cerulein and
azoxymethane via intraperitoneal administration developed pathological malignant phenotype, as well as
concomitant lung inflammation.

Results:
We discovered pathological alterations in the pancreas that were associated with chronic pancre-atitis, including a buildup of eosinophilic inflammation. Eosinophil degranulation was reported nearby in the pancreas tissue sections that show acinar-to-ductal metaplasia and acinar cell atrophy, both of which are characteristic of pancreatic malignancies. Additionally, we also observed the formation of PanIN lesions after three initial doses of AOM and eight weeks of cerulein with the AOM treatment regimen. We discov-ered that persistent pancreatic eosinophilic inflammation linked with a pancreatic malignant phenotype contributes to pulmonary damage. The RNA seq analysis also confirmed the induction of fibro-inflamma-tory and oncogenic proteins in pancreas and lung tissues. Further, in the current manuscript, we now report the stepwise kinetically time-dependent cellular inflammation, genes and proteins involved in the develop-ment of pancreatitis malignancy and associated acute lung injury by analyzing the mice of 3 AOM with 3, 8, and 12 weeks of the cerulein challenged protocol regime.

Conclusion:
We first show that sustained long-term eosinophilic inflammation induces time-dependent proinflammatory, profibrotic and malignancy-associated genes that promote pancreatic malignancy and acute lung injury in mice.
Correlation of Serum Uric Acid with Cognition, Severity, and Stage of Disease in Patients with Idiopathic Parkinson’s Disease and Vascular Parkinsonism: A Cross-Sectional Study
Authors: Misri Zulkifli , Pillarisetti Shashank , Nayak Pradeepa , Mahmood Amreen , Ahmed Safwan , Unnikrishnan Bhaskaran 
Published: August 2022

Background:
Uric acid (UA) being a potent antioxidant may reduce the oxidative stress and progression of Parkinson’s disease. However, the role of UA is not yet established in people with Idiopathic Parkinson’s disease (IPD) and Vascular Parkinsonism (VP).

Objectives:
We aimed i) to compare the serum UA levels in IPD, VP, and healthy adults and ii) to find a relation between UA levels with disease severity, disease stage, and cognitive function in people with IPD and VP.

Methods:
A cross-sectional study was conducted among people with IPD (n=70), VP (n=70), and healthy adults (n=70). Demographics details, body mass index, duration of illness, levodopa usage, comorbidities, MDS-UPDRS scores, modified H&Y scale, MMSE, and serum UA levels were collected from participants. Pearson’s correlation coefficient was used to find the correlation between UA levels, MDS-UPDRS, H & Y, and MMSE scores.

Results:
The age of the participants ranged from 59 to 80 years. Results showed that serum UA level in healthy control (5.41±0.99; p=0.001) and VP groups (5.27 ± 0.99; p=0.001) were significantly higher compared to IPD group (4.34 ±1.03). We found a significant negative correlation between UA and MDS-UPDRS (r=-0.68, p<0.01) and H & Y scores (r = -0.61, p<0.01) and a significant positive correlation of UA with MMSE (r=0.55, p<0.01) in the IPD group. UA levels in the VP group were not correlated with any of the outcome measures.

Conclusion:
In people with IPD, serum UA level was negatively correlated with severity and progression of the disease but positively correlated with cognitive ability.
Discovery and Design of Radiopharmaceuticals by In silico Methods
Authors: Winkler David A. , Salahinejad Maryam , Shiri Fereshteh 
Published: August 2022

Abstract:There has been impressive growth in the use of radiopharmaceuticals for therapy, selective toxic payload delivery, and noninvasive diagnostic imaging of disease. The increasing timeframes and costs involved in the discovery and development of new radiopharmaceuticals have driven the development of more efficient strategies for this process. Computer-Aided Drug Design (CADD) methods and Machine Learning (ML) have become more effective over the last two decades for drug and materials discovery and optimization. They are now fast, flexible, and sufficiently accurate to accelerate the discovery of new molecules and materials. Radiopharmaceuticals have also started to benefit from rapid developments in computational methods. Here, we review the types of computational molecular design techniques that have been used for radiopharmaceuticals design. We also provide a thorough examination of success stories in the design of radiopharmaceuticals, and the strengths and weaknesses of the computational methods. We begin by providing a brief overview of therapeutic and diagnostic radiopharmaceuticals and the steps involved in radiopharmaceuticals design and development. We then review the computational design methods used in radiopharmaceutical studies, including molecular mechanics, quantum mechanics, molecular dynamics, molecular docking, pharmacophore modelling, and datadriven ML. Finally, the difficulties and opportunities presented by radiopharmaceutical modelling are highlighted. The review emphasizes the potential of computational design methods to accelerate the production of these very useful clinical radiopharmaceutical agents and aims to raise awareness among radiopharmaceutical researchers about computational modelling and simulation methods that can be of benefit to this field.