bluuebunny/crossref_metadata_2025_split huggingface dataset:
Full-scale determination of pipe wall and bulk chlorine degradation coefficients for different pipe categories
Authors: Maleki Mahnoush , Ardila Andres , Argaud Pierre-Olivier , Pelletier Genevieve , Rodriguez Manuel 
Published: January 2023

Abstract
Having good information about parameters that impact water quality can improve the management of water distribution systems in the short-term (optimising disinfection) and the long-term (planning rehabilitation). Full-scale data on the degradation of the residual disinfectant for various pipe characteristics are difficult to obtain but necessary. As the most common disinfectant is chlorine, this paper aims to determine the most important pipe and/or hydraulic system characteristics in the chlorine degradation coefficients. Such characteristics were identified based on statistical analyses that relate them with range values of bulk and pipe wall degradation coefficients estimated in full-scale conditions in a real distribution system. The results showed that among pipe characteristics, the period of installation impacts significantly kw and kt. Results of kw for three different materials confirmed that residual chlorine degradation at the pipe walls for grey-cast iron, which is older and metallic, is much higher than that for ductile cast iron and PVC pipes. In older pipes, up to 97% of residual chlorine can be degraded at the pipe walls, while the role of bulk reactions can reach about 35% in newer pipes. The obtained information can be integrated to identify pipes for rehabilitation/renewal and locations for booster rechlorination.
The Protective Effects of Silymarin on the Reproductive Toxicity: A Comprehensive Review
Authors: Hariyanti Tita , Margiana Ria , Al-Gazally Moaed Emran , Patra Indrajit , Lateef Al-Awsi Ghaidaa Raheem , Hameed Noora , Kayumova Dilrabo , Ansari Mohammad Javed , Torres-Criollo Larry Miguel , Mustafa Yasser Fakri , Abedi-Firouzjah Razzagh , Farhood Bagher 
Published: January 2023

Abstract:The reproductive system is extremely vulnerable to chemotherapy drugs, ionizing radiation, toxic heavy metals, chemicals, and so on. These harmful stimuli are able to induce oxidative damage, apoptosis, inflammation, and other mechanisms in the reproductive organs, leading to different adverse reproductive effects. It was shown that using medicinal plants (medicinal herbs) can be an effective medication for the prevention and treatment of multiple health conditions. Silymarin is a medicinal herb extract, obtained from the seeds of Silybum marianum. This herbal agent is a nontoxic agent even at relatively high physiological dose values, which suggests that it is safe for use in the treatment of different diseases. The hepato-, neuro-, cardio- and nephro-protective effects of silymarin have been assessed previously. The protective activities of silymarin can point to anti-oxidant, anti-apoptotic, anti-inflammatory, anti-fibrotic, immunomodulatory, and membrane-stabilizing properties. In this review, we aim to summarize current studies on the protective potentials of silymarin against reproductive toxicity. The molecular mechanisms of silymarin protection against cellular toxicity are also studied. Moreover, the findings obtained from improved formulations and delivery systems of silymarin have been addressed.
Peptide-based PROTACs: Current Challenges and Future
Perspectives
Authors: Wang Huidan , Chen Miao , Zhang Xiaoyuan , Xie Songbo , Qin Jie , Li Jingrui 
Published: January 2023

Abstract:
Proteolysis-targeting chimeras (PROTACs) are an attractive means to target
previously undruggable or drug-resistant mutant proteins. While small molecule-based
PROTACs are stable and can cross cell membranes, there is limited availability of suitable
small molecule warheads capable of recruiting proteins to an E3 ubiquitin ligase for
degradation. With advances in structural biology and in silico protein structure prediction,
it is now becoming easier to define highly selective peptides suitable for PROTAC
design. As a result, peptide-based PROTACs are becoming a feasible proposition for targeting
previously “undruggable” proteins not amenable to small molecule inhibition. In
this review, we summarize recent progress in the design and application of peptide-based
PROTACs as well as several practical approaches for obtaining candidate peptides for
PROTACs. We also discuss the major hurdles preventing the translation of peptide-based
PROTACs from bench to bedside, such as their delivery and bioavailability, with the aim
of stimulating discussion about how best to accelerate the clinical development of peptide-
based PROTACs in the near future.
Circulating Levels of 5-HT and BDNF in Adults with Autism
Spectrum Conditions: An Investigation in a Sample of Subjects with
Autism Spectrum Disorder, their First-degree Relatives and Controls
Authors: Carpita Barbara , Stagnari Rossella , Palego Lionella , Baroni Dario , Massimetti Gabriele , Nardi Benedetta , Cremone Ivan Mirko , Betti Laura , Giannaccini Gino , Dell'Osso Liliana 
Published: January 2023

Background:
Several studies investigated circulating levels of serotonin (5-
HT) and brain-derived neurotrophic factor (BDNF) in children with Autism spectrum disorder
(ASD). More limited literature focused on ASD adults or on populations with subthreshold
autism spectrum manifestations, such as relatives of ASD probands. This study
aimed to investigate 5-HT and BDNF levels in adults with autism spectrum conditions.
Correlations between levels of biochemical variables and ASD symptoms were also evaluated.

Methods:
a sample of ASD adults, their first-degree relatives (Broad autism phenotype,
BAP group), and controls were recruited and assessed with psychometric scales. Blood
samples were collected from all participants. 5-HT and BDNF levels were measured by
means of ELISA kits.

Results:
ASD adults showed significantly lower platelet-poor plasma (PPP) 5-HT levels
than BAP and control groups. No significant difference was found among groups for PPP
BDNF levels and intra-platelet 5-HT levels. 5-HT levels were reported to be specifically
correlated with some autism symptoms.

Conclusion:
This work highlighted the presence in ASD adults of reduced PPP 5-HT levels
than in other groups, without significant differences with respect to BDNF levels, supporting
the hypothesis that biochemical correlates of ASD in adults may be different
from those typically reported in children.
Scutellarin Suppressed Proliferation and Induced Apoptosis in Gastric Cancer
via Wnt/β-catenin Signaling Pathway
Authors: Liu Zheng , Wang Zhenkai , Liu Xiang , Chen Wanzhen , Guo Xiujun , Chen Lili , Wei Zhiqin , Liu Dan 
Published: January 2023

Background:
Scutellarin exerts anticancer effects on diverse malignancies. However, its function in gastric cancer has not been explored.

Objective:
This study aimed to examine the anticancer effect and molecular mechanism of scutellarin in gastric cancer.

Materials and Methods:
Gastric cancer cells were treated with scutellarin and transfected with the Wnt1 overexpression plasmid. Cell viability, proliferation, toxicity, and apoptosis were determined by cell counting kit-8 (CCK-8), colony formation, lactate dehydrogenase (LDH) activity, TdT-mediated dUTP Nick-End Labeling (TUNEL), and flow cytometry assays. Expressions of apoptosis-related and Wnt/β-catenin signaling pathway-related proteins were examined by western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results:
Scutellarin concentration dependently restrained cell viability. Scutellarin (20 and 80 μmol/L) suppressed proliferation and promoted LDH release and apoptosis. Moreover, scutellarin elevated Bax and Cytochrome C levels but diminished the levels of Bcl-2, Wnt1, cytoplasmic β-catenin, and basal cytoplasmic β-catenin. However, the above-mentioned regulatory effects of scutellarin were all reversed by Wnt1 overexpression.

Conclusion:
Scutellarin suppressed gastric cancer cell proliferation and promoted apoptosis by inhibition of the Wnt/β-catenin pathway.
Physiologically-Based Pharmacokinetic Modeling of Tenofovir Disoproxil Fumarate
in Pregnant Women
Authors: Zhang Xiqian , Luo Tao , Yang Huan , Ma Wan Ying , He Qin , Xu Min , Yang Yujie 
Published: January 2023

Purpose:
Physiological changes during pregnancy can affect antiretroviral drug processes and further influence
drug efficacy and safety. Physiologically-based pharmacokinetic (PBPK) modeling offers a unique modality to
predict PK in pregnant women. The objective of this study was to establish a PBPK modeling of tenofovir disoproxil
fumarate (TDF) in pregnant women, to provide a reference for the clinical use of TDF.

Methods:
A full PBPK modeling of tenofovir (TFV) and TDF following i.v. and p.o. administration was developed
using the simulation software PK-Sim®. The modeling was then extrapolated to pregnant women based on pregnancyrelated
physiological parameters in Mobi® Simulator. The mean fold error (MFE) and geometric mean fold error
(GMFE) methods were used to compare the differences between predicted and observed values of PK parameters
(Cmax, tmax, AUC0-∞) to evaluate the accuracy of PBPK modeling.

Results:
The developed PBPK modeling successfully predicted the TDF disposition in the non-pregnant population,
wherein the MFE average and GMFE of all predicted PK parameters were within a 1.5-fold error range, and more than
96.30% of the predicted drug concentration values were within a 2-fold error range of the measured values. After the
extrapolation of these models to the third trimester of pregnancy, the scaling anatomy/physiology and hepatic intrinsic
clearance made the pregnant population PBPK modeling meet the standard requirement of 0.5 < MFE and GMFE
value < 2. It was more appropriate to simulate the in vivo process of low-dose TDF in pregnant women.

Conclusion:
The non-pregnant population PBPK modeling of TDF established in our study can be extrapolated to
pregnant women. Our study provides a reference for realizing clinical personalized medication for pregnant women.
A Comprehensive Study on the Chemical Constituents and Pharmacokinetics of
Erzhi Formula and Jiawei Erzhi Formula Based on Targeted and Untargeted LC-MS
Analysis
Authors: Zhu Tongtong , Chen Wanning , Han Chunyue , Gao Zhijie , Liu Erwei , Gao Xiumei , Fu Zhifei , Han Lifeng 
Published: January 2023

Background:
Erzhi formula (EZF) is a traditional Chinese medicine prescription, which has been widely used in the treatment of osteoporosis and premature ovarian failure.

Objective:
To enhance curative effects, the other two herbal medicines, including Spatholobi Caulis (SC) and Achyranthes bidentata Blume (ABB), were added into the original EZF formula to obtain two new Jiawei-EZF (JW-EZF) preparations. To clarify the effect of the compatibility of herbs for original formulas, the chemical constituents and bioactive compounds in vivo were detected.

Methods:
An efficient and sensitive targeted and untargeted UHPLC/ESI-Q-Orbitrap MS method, together with mass defect filter and precursor ion list, was established firstly for the profiling of different EZF formulas. Furthermore, eleven absorbed compounds (apigenin, luteoloside, luteolin, oleuropein, wedelolactone, acteoside, specnuezhenide, 11-methyloleoside, ecliptasaponin A, formononetin, and β-ecdysone) were simultaneously quantified in rat plasma.

Results:
A total of 124, 162, and 177 compounds were identified or tentatively identified in EZF, JW-3-EZF (EZF+SC) and JW-4-EZF (EZF+SC+ABB), respectively. 110 compounds were found to be common constituents in the three formulas. Moreover, 66 prototypes were unambiguously identified in the rats' plasma after oral administration of the three formulas using the same strategy. 11 out of the 66 absorbed components were simultaneously quantitated in the pharmacokinetic (PK) study. Compared to the original EZF, the plasma AUC(0-24h) and AUC(0-∞) of apigenin, 11-methyloleoside, luteolin, luteoloside, wedelolactone, and acteoside were found to be significantly increased after oral administration of JW-3-EZF, and plasma AUC(0-24h) and AUC(0-∞) of apigenin, wedelolactone, and acteoside, were also found to be significantly increased after JW-4-EZF administration.

Conclusion:
The combined qualitative and quantitative methods were used to provide a potential approach to the characterization and quality control of the Traditional Chinese Medicine (TCM) and its preparations.
Metabolic-associated Fatty Liver Disease Regulation through Nutri Epigenetic
Methylation
Authors: Rivera-Aguirre Jesus , López-Sánchez Guillermo Nahúm , Chávez-Tapia Norberto Carlos , Uribe Misael , Nuño-Lámbarri Natalia 
Published: January 2023

Abstract:
Metabolically associated fatty liver disease, formerly called nonalcoholic fatty liver disease,
is the most common liver disease globally, representing the third cause of liver transplantation.
Metabolically associated fatty liver disease is defined as having more than 5% lipid droplets in
hepatocytes without other concomitant liver diseases. Various stimuli such as the secretion of inflammatory
cytokines, mitochondrial and endoplasmic reticulum dysfunction due to oxidative stress, alteration
of the intestine-liver axis, bacterial dysbiosis, as well as genetic and epigenetic factors can modify
the progression of metabolically associated fatty liver disease to fibrosis, cirrhosis, and may reach
hepatocellular carcinoma. Epigenetics is responsible for a highly sophisticated regulatory system that
controls many cellular processes in response to multiple environmental factors as an adaptive mechanism
unrelated to alterations in the primary deoxyribonucleic acid sequence, including gene expression,
microRNAs, DNA methylation, modifications in histones, and DNA-protein interactions. Several
studies have shown that epigenetic changes are associated with various diseases, including metabolically
associated fatty liver disease. Nutri epigenomics is the interaction between nutrition and components
at the transcriptional or post-transcriptional level. Methylation processes involve micronutrients
that regulate epigenetic states in a physiological and pathological context. Micronutrients such as
methionine, folate, and choline are the main components of one-carbon metabolism, functioning as
methyl group donors, and their deficiency predisposes to various pathologies such as metabolically
associated fatty liver disease. Understanding of epigenetic modifiers leads us to develop new therapeutic
therapies for patients with metabolically associated fatty liver disease.
Twin Anemia-Polycythemia Sequence (TAPS): From Basic Research to
Clinical Practice
Authors: da Silva Rocha Joana , Guedes-Martins Luís , Cunha Ana 
Published: January 2023

Abstract:
Twin pregnancy is associated with an increased risk of perinatal and maternal complications,
and early establishment of the chorionicity type defines this risk. In monochorionic (MC) pregnancies,
the fetuses share the same placental mass and exhibit vascular anastomoses crossing the intertwin membrane,
and the combination and pattern of anastomoses determine the primary clinical picture and occurrence
of future complications.

:
Twin Anemia-Polycythemia Sequence (TAPS) was first described in 2006 after fetoscopic laser surgery
in twin-to-twin transfusion syndrome (TTTS) twins, and in 2007, the first spontaneous cases were reported,
recognizing TAPS as an individualized vascular identity in fetofetal transfusion syndromes.
There are two types of TAPS: spontaneous (3-5%) and iatrogenic or postlaser (2-16%). TAPS consists
of small diameter arteriovenous anastomoses (<1 mm) and low-rate, small-caliber AA anastomoses in
the absence of amniotic fluid discordances. There are certain antenatal and postnatal diagnostic criteria,
which have progressively evolved over time. New, additional secondary markers have been proposed,
and their reliability is being studied. The best screening protocol for TAPS in MC twins is still a matter
of debate.

:
This review provides a survey of the relevant literature on the epidemiology, vascular pathophysiology,
underlying hemodynamic factors that regulate mismatched vascular connections, and diagnostic criteria
of this condition. The aim is to increase awareness and knowledge about this recently identified and
frequently unrecognized and misdiagnosed pathology.
Acetylsalicylic Acid (Aspirin) for Primary Prevention of Cardiovascular
Events in Patients with Diabetes: A Systematic Review and Meta-Analysis
of Randomized Controlled Trials
Authors: Liu Shuangbo , Eckstein Janine , Lam Anna , Cheema Asim N. 
Published: January 2023

Background:
Evidence regarding using acetylsalicylic acid (aspirin) for the prevention of
cardiovascular (CV) events in patients with diabetes mellitus (DM) is inconsistent. Therefore, we performed
a meta-analysis.

Methods:
A literature search was performed (January 1990 to February 2022) and publications meeting
the inclusion criteria were reviewed, and a meta-analysis was performed using RevMan software. The
primary outcome was a composite of CV death, non-fatal myocardial infarction (MI) and stroke. Secondary
outcomes included all-cause mortality, individual components of the primary outcome and major
bleeding.

Results:
The study cohort comprised 33525 diabetic patients from 9 randomized controlled trials. The
primary outcome was significantly lower for aspirin vs. placebo (7.9 vs. 8.6, RR (risk ratio) 0.92, 95%
CI (confidence interval) 0.86-0.99). All-cause mortality (10 vs. 10.3%, RR 0.97, 95% CI 0.90-1.03), CV
death (4.4 vs. 4.7%, RR 0.93, 95% CI 0.83-1.04), non-fatal MI (4.6 vs. 4.8% RR 0.97, 95% CI 0.83-
1.15) and stroke (3.2 vs. 3.5%, RR 0.89, 95% CI 0.75-1.06) were similar between the two treatment
groups. Major bleeding was significantly higher for aspirin compared with placebo (3.4 vs. 2.8%, RR
1.18, 95% CI 1.01-1.39).

Conclusion:
Aspirin use in patients with DM reduces the composite endpoint of CV death, non-fatal MI
and stroke compared with a placebo. However, routine use of aspirin for primary prevention among
diabetic patients cannot be advised due to the increased risk of major bleeding. These findings suggest
careful risk assessment of individual patients.
Clinical and Laboratory Evaluation of Acute Pericarditis Associated with
Antinuclear Antibodies Positivity
Authors: Dursun Ali Doğan , Saricam Ersin , Erdem Hakan , Sariyildiz Gulcin Turkmen , Ozyer Esref Umut , Bozkurt Engin , Ilkay Erdogan , Cantekin Ömer Faruk 
Published: January 2023

Background:
Up to 30% of patients with acute pericarditis develop recurrent pericarditis.
Acute pericarditis may be a manifestation of an underlying systemic autoimmune disease. Therefore, we
evaluated the characteristics of patients with acute pericarditis according to antinuclear antibodies
(ANA) positivity/negativity.

Methods:
Participants with acute pericarditis and negative ANA (n=29), recurrent pericarditis with positive
ANA (n=30) and healthy controls (n=11) were examined. The groups were compared using serum
parameters (ANA, C-reactive protein, leucocyte count, erythrocyte sedimentation rate, total antioxidant
status, nitric oxide (NO), and oxidative stress index (OSI)) and imaging techniques (electrocardiogram,
echocardiography, cardiovascular magnetic resonance, and venous Doppler ultrasound).

Results:
In females, acute pericarditis associated with ANA occurred more frequently (p<0.001). ANApositive
acute pericarditis had significantly lower NO and OSI (p<0.05 and p<0.001, respectively) and
pericardial inflammation on magnetic resonance. We found a pulmonary embolism in one patient with
positive ANA. Slow venous flow (SVF) occurred more often in acute pericarditis associated with ANA
than in the ANA-negative group on venous ultrasound (p<0.05). The prevalence of positive ANAs was
1.6 times higher among SVF patients than in controls.

Conclusion:
This study suggests that acute pericarditis associated with ANA is more common in middle-
aged females. SVF and lower oxidative stress tests were more common in patients with ANAassociated
acute pericarditis. Acute pericarditis associated with ANA could be considered as a hypercoagulable
state. Therefore, all newly diagnosed pericarditis patients (especially females) should be
checked for ANA positivity. Awareness of this coexistence should be promptly addressed to establish
management strategies.
Synthesis and Mesomorphic Properties of New Non-symmetric Liquid
Crystal Dimers
Authors: Ha Sie-Tiong , Seou Chi-Kien , Win Yip-Foo , Yeap Guan-Yeow 
Published: January 2023

Abstract:
New non-symmetric liquid crystal dimers, N-(4-(n-(4-(benzothiazol-2-yl)phenoxy) alkyloxy)
benzylidene)-2,4-difluoroaniline (DSFCn), containing two mesogenic core units of benzothiazole
and benzylideneaniline were reported. The core system was connected by a flexible alkyl spacer,
-(CH2)n-(where n =2-6, 8, 10, and 12). The spectroscopic techniques were employed to confirm the
molecular structure of the title compounds. Differential scanning calorimetry and polarizing optical
microscopy were used to study the mesomorphic properties of the synthesized compounds. Observation
under crossed polarized light reveals that compounds (n = 4, 5, 6, 8, 10, 12) are purely nematogens.
The nematic phase in the dimers are caused by the presence of the lateral fluorine atoms at the
benzylideneaniline core. Mesophase thermal stability has been suppressed significantly by the fluorine
atom at the lateral position which increased the molecular breadth and subsequently, results in weaker
overall lateral intermolecular attraction. The structure-property relationships of the dimers were inferred
through comparison of thermal properties of the present dimers with those of the earlier reported
analogous that do not possess any lateral substituents.
DMAP-Promoted Cascade Reaction of α-Ketoester with Benzylidene-
Malononitrile: Access Polyfunctionalized 2-Amino-3-Cyano-4H-Pyran
Containing Ester Motifs
Authors: Zhang Chuan-Bao , Wang Hong-Tao , Zhao Ze-Yue , Lou Li-Fang , Zhao Jiang-Tao , Geng Yang , Zhai Bai-Qiang , Tian Ye 
Published: January 2023

Abstract:
A base-promoted cascade reaction of α-ketoester with benzylidene-malononitrile was
developed under mild reaction conditions, which enabled the synthesis of polyfunctionalized 2-amino-
3-cyano-4H-pyrans containing ester motifs at 6-position with good to excellent yields. These transformations
not only construct various polyfunctionalized 4H-pyrans, which add a new member to the
family of 4H-pyrans, but also provide an efficient approach for the synthesis of fully substituted 4Hpyran
derivatives.