bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the impact of Nalla Lai contamination on drinking quality of groundwater in Rawalpindi city, Pakistan
Authors: Khan Shahid Ali , Rafiq Muhammad Tariq , Shah Farzana Altaf , Aziz Rukhsanda , Din Islamud , Yasir Ammar , Iqbal Asif 
Published: December 2022

Abstract
The scientific report assessed the impact of Nalla Lai wastewater on the groundwater quality of Rawalpindi city, Pakistan. A total of 19 wastewater and 49 groundwater samples were collected during September and October 2016 and have been analyzed in the laboratory to detect different water quality parameters. The results revealed that BOD (biological oxygen demand), COD (chemical oxygen demand), iron, and cadmium values in many wastewater samples were beyond the recommended value of the National Environmental Quality Standards 1997 (NEQs, 1997). In groundwater samples, the results of iron, cadmium, manganese, zinc, TDS (total dissolved solids), pH, color, and hardness were found elevated from the standard values in one or more samples as compared with the National Standard for Drinking Water Quality, 2010 (NSDWQ, 2010). The decreasing metal concentration order in groundwater samples was iron &gt; zinc &gt; manganese &gt; copper &gt; cadmium. Very interestingly, hardness was found at elevated levels in 75% of investigated groundwater samples. Microbiological contamination was detected in 83% of the analyzed groundwater samples. The study revealed the percolation of heavy metals and microbial contamination in the bore water, tube wells, hand pumps, springs, and hand-dug wells located nearby the Nalla Lai wastewater stream.
Urban flood resilience assessment using RAGA-PP and KL-TOPSIS model based on PSR framework: A case study of Jiangsu province, China
Authors: Ji Juan , Chen Junfei 
Published: December 2022

Abstract
The research on urban flood resilience will contribute to building a more resilient city and provide valuable reference for municipal decision-makers. There are many frameworks and approaches for empirical studies on what constitutes urban flood resilience and how to evaluate it. In this study, a typical region suffering from flood disaster in China-Jiangsu Province was selected as the study area, including 13 prefecture-level cities. The pressure-state-response (PSR) framework, the projection pursuit based on real-coded accelerated genetic algorithm (RAGA-PP) and the technique for order preference by similarity to an ideal solution based on the Kullback-Leibler distance (KL-TOPSIS) were combined to develop a hybrid multi-criteria approach for assessing urban flood resilience. Then the grey relational analysis obtained the important factors. The results illustrate that (1) the development of each subsystem in the city is uncoordinated, that is, the pressure-subsystem has little influence on urban flood resilience, while the state-subsystem and the response-subsystem have great influence. (2) The urban flood resilience in Jiangsu Province presents obvious polarization trend, that is, Southern Jiangsu is more resilient than Northern Jiangsu. The underlying factors are closely related to the level of economic development. Furthermore, the proposed method provides a practical evaluation approach for other fields.
Genetic Testing is Superior Over Endogenous Pharmacometabolomic Markers to
Predict Safety of Haloperidol in Patients with Alcohol-induced Psychotic Disorder
Authors: Skryabin Valentin , Zastrozhin Mikhail , Parkhomenko Alexandra , Lauschke Volker M. , Smirnov Valery , Petukhov Aleksey , Pankratenko Elena , Pozdnyakov Sergei , Koporov Sergei , Denisenko Natalia , Akmalova Kristina , Bryun Evgeny , Sychev Dmitry 
Published: December 2022

Background:
Previous studies have shown that haloperidol biotransformation is mainly metabolized by
CYP2D6. The CYP2D6 gene is highly polymorphic, contributing to inter-individual differences in enzymatic activity,
and may impact haloperidol biotransformation rates, resulting in variable drug efficacy and safety profiles.

Objective:
The study aimed to investigate the correlation of the CYPD6 activity with haloperidol's efficacy and safety
rates in patients with alcohol-induced psychotic disorders.

objective:
To investigate the correlation of the CYPD6 activity with the efficacy and safety rates of haloperidol in patients with alcohol-induced psychotic disorders.

Method:
One hundred male patients received 5-10 mg/day haloperidol by injections for 5 days. The efficacy and
safety assessments were performed using PANSS, UKU, and SAS-validated psychometric scales.

Results:
No relationship between haloperidol efficacy or safety and the experimental endogenous pharmacometabolomic
marker for CYP2D6 activity, urinary 6-НО-ТНВС/pinoline ratio was identified. In contrast, we found a statistically
significant association between haloperidol adverse events and the most common CYP2D6 loss-of-function
allele CYP2D6*4 (p<0.001).

Conclusion:
Evaluation of the single polymorphism rs3892097 that defines CYP2D6*4 can predict the safety profile
of haloperidol in patients with AIPD, whereas metabolic evaluation using an endogenous marker was not a suitable
predictor. Furthermore, our results suggest haloperidol dose reductions could be considered in AIPD patients with at
least one inactive CYP2D6 allele.
The Influences and Mechanisms of High-altitude Hypoxia Exposure on Drug Metabolism
Authors: Zhao Anpeng , Li Wenbin , Wang Rong 
Published: December 2022

Background:
The special environment of high-altitude hypoxia not only changes the physiological state
of the body but also affects the metabolic process of many drugs, which may affect the safety and efficacy of these
drugs. The number of drugs is huge, so it is not wise to blindly repeat the pharmacokinetic studies of all of them on
the plateau. Mastering the law of drug metabolism on the plateau is conducive to the comprehensive development of
rational drug use on the plateau. Therefore, it is very important to determine the impacts and elucidate the mechanism
of drug metabolism in hypobaric hypoxia conditions.

Methods:
In this review, we searched published studies on changes in drug metabolism in hypoxia conditions to
summarize and analyze the mechanisms by which hypoxia alters drug metabolism.

Results:
Although the reported effects of high-altitude hypoxia on drug metabolism are sometimes controversial,
metabolism kinetics for most of the tested drugs are found to be affected. Mechanism studies showed that the major
reasons causing metabolism changes are: regulated drug-metabolizing enzymes expression and activity mediated by
HIF-1, nuclear receptors and inflammatory cytokines, and change in direct or indirect effects of intestinal microflora
on drug metabolism by itself or the host mediated by microflora-derived drug-metabolizing enzymes, metabolites,
and immunoregulation.

Conclusion:
Altered enzyme expression and activity in the liver and altered intestinal microflora are the two major
reasons to cause altered drug metabolism in hypoxia conditions.
A Systematic Review of Linezolid Pharmacokinetics/Pharmacodynamics in Patients
Undergoing Continuous Renal Replacement Therapy: Does One Size Fit All?
Authors: Liu Yao , Ge Xu-Hua , Guo Hong-Li , Chen Feng , Zhang Yong , Xu Jing , Ji Xing , Miao Hong-jun 
Published: December 2022

Background:
Selection of the optimal antimicrobial posology in critically ill patients remains a challenge,
especially in patients with sepsis who undergo continuous renal replacement therapy (CRRT). This systematic review
aimed to analyze factors that influence the extracorporeal removal of linezolid.

Methods:
A comprehensive search was performed to identify studies published up to March 2022 in PubMed,
MEDLINE and EMBASE databases. Studies involving adults receiving CRRT and treatment with linezolid were
considered eligible if the CRRT setting and linezolid’s pharmacokinetic parameters were clearly mentioned.

Results:
Six out of 110 potentially relevant studies were included. A total of 101 treatments were identified among
97 enrolled patients. Our analysis showed that continuous veno-venous hemodiafiltration (CVVHDF) was the most
frequential used modality (52 cases). Despite distribution volume, the clearance (CL) of linezolid in these studies had
large variability. Extracorporeal linezolid removal may be markedly impacted by CRRT dose. There is significant
between-subject variability in the probability of pharmacokinetics-pharmacodynamics (PK-PD) target attainment of
patients treated with CRRT.

Conclusion:
Dose adjustment, shortening the dosing interval, and continuous infusion were proposed as regimen
optimization. Therapeutic drug monitoring is recommended due to the high variability of linezolid exposure among
patients with CRRT, specifically for those whose bodyweight is high, renal function is preserved, and the MIC of
infection bacteria is above 2 μg/mL.
Drug Discovery to Drug Development of BACE1 Inhibitor as Antialzheimer’s:
A Review
Authors: Munj Sonali Mehendale , Patil Pooja Bhagwan 
Published: December 2022

Abstract:
Alzheimer’s Disease (AD) is a complex and progressive neurodegenerative disease, and the most common cause of dementia usually occurs due to old age. Production and accumulation of amyloid-β peptide (Aβ) represent the major pathological event of the disease. The formation of am-yloid-β results due to proteolytic cleavage of amyloid precursor protein (APP) by beta-site amyloid precursor protein cleaving enzyme (BACE1) shown as the amyloid hypothesis, a prevalent theory for AD pathogenesis. Thus, BACE1 represents a novel target to decrease cerebral Aβ concentration and slow down the disease’s progression. The structure-based drug design approach led to a wide variety of small molecules with the mechanism of action centered around inhibition of β-secretase protease (BACE1), which are shown to have drug-like properties and reduce brain Aβ levels. Based on transition state isosteres, BACE1 inhibitors can largely be classified as peptidomimetics and non-peptidomimetics. The subclasses of the two categories have been covered with different scaf-folds like statin, norstatin, carbinamine, hydroxyethylene, hydroxyethylamine, acyl guanidine, 2-aminopyridine, aminoimidazole, aminohydantoin, aminothiazoline, aminooxazoline, aminoquino-line, piperazine-based. Among these small molecules, those who fulfilled general requirements for a drug aimed at the central nervous system (CNS) and selectivity over other aspartyl proteases reached the final pipeline of clinical trials. Here, in this review, we summarize the journey of BACE1 inhibitors through different practices of drug design development, Structural Activity Rela-tionship (SAR), and other inhibitor candidates that are currently in clinical trials as BACE1 inhibi-tors.
Computed Tomography-guided Techniques for Localizing Pulmonary
Nodules by Localization Needle versus Methylene Blue
Authors: Kong Jian , Zhang Hua , Guo Jian-Xi 
Published: December 2022

Objective:
The aim of this study was to evaluate the clinical value of computed tomography-guided localization needle (LN) and methylene blue (MB) for pulmonary nodule localization.

Materials and Methods:
Between November 2019 and January 2022, 547 patients underwent computed tomography-guided LN (n=171) or MB (n=376) localization and video-assisted thoracoscopic surgery (VATS) resection.

Results:
In total, 171 and 376 nodules were localized via LN and MB, respectively, with respective
technical localization success rates of 92.98 % and 88.56 % (p = 0.111). The pulmonary nodule localization
time was significantly shorter for the MB group than for the LN group (p < 0.05). However, the
rates of total complication, chest pain, and cough were significantly lower in the LN group (χ2 =
8.251/25.092/5.127, all p < 0.05). Furthermore, the LN group had a shorter VATS time than the MB
group (p < 0.05). The VATS achieved a 100% operation success rate in both groups, and there was no
significance between groups with respect to the types of surgery (p > 0.05) or the blood loss (p >
0.05). Moreover, logistic regression analysis showed that the localization technique was an independent
risk factor for total complications and chest pain.

Conclusion:
Both techniques can effectively localize pulmonary nodules before VATS. MB had a shorter localization time, but the LN had a shorter VATS time and a lower incidence of complications, especially chest pain.
Study on the Crush Injury Model of the Sciatic Nerve in Rabbits by Conventional
Ultrasound and Elastography
Authors: Qi Hengtao , Wang Tiezheng , Chen Chao , Teng Jianbo 
Published: December 2022

Background:
The crush injury model of the sciatic nerve in rabbits is a common nerve injury
model, but there is little literature on the evaluation of nerve stiffness by ultrasound elastography.

Purpose:
To explore the value of ultrasound elastography in diagnosing crush injury of the sciatic
nerve in rabbits.

Materials and Methods:
Forty cases of crush injury model of the sciatic nerve in rabbits were examined
by conventional ultrasound and elastography. The sonographic manifestations and stiffness of the
model were analyzed, and the regularity of nerve injury with time was summarized.

Results:
Ultrasound could clearly show the location, range, and thickness of the injured nerve in this
model. The thickness of the injured area reached a peak in the 2nd week and returned to normal thickness
in the 8th week. The nerve stiffness of the injured area increased gradually with time.

Conclusions:
Conventional ultrasound combined with elastography can comprehensively and quantitatively
evaluate the morphological changes and mechanical properties of the injured sciatic nerve in
rabbits, which may be of great significance to the repair and rehabilitation of peripheral nerve crush
injuries.
Role of Potassium Ion Channels in Epilepsy: Focus on Current
Therapeutic Strategies
Authors: Khan Rahul , Chaturvedi Pragya , Sahu Prachi , Ludhiadch Abhilash , Singh Paramdeep , Singh Gagandeep , Munshi Anjana 
Published: December 2022

Background:
Epilepsy is one of the prevalent neurological disorders characterized by disrupted
synchronization between inhibitory and excitatory neurons. Disturbed membrane potential due
to abnormal regulation of neurotransmitters and ion transport across the neural cell membrane significantly
contributes to the pathophysiology of epilepsy. Potassium ion channels (KCN) regulate the resting
membrane potential and are involved in neuronal excitability. Genetic alterations in the potassium
ion channels (KCN) have been reported to result in the enhancement of the release of neurotransmitters,
the excitability of neurons, and abnormal rapid firing rate, which lead to epileptic phenotypes,
making these ion channels a potential therapeutic target for epilepsy. The aim of this study is to explore
the variations reported in different classes of potassium ion channels (KCN) in epilepsy patients,
their functional evaluation, and therapeutic strategies to treat epilepsy targeting KCN.

Methodology:
A review of all the relevant literature was carried out to compile this article.

Result:
A large number of variations have been reported in different genes encoding various classes of
KCN. These genetic alterations in KCN have been shown to be responsible for disrupted firing properties
of neurons. Antiepileptic drugs (AEDs) are the main therapeutic strategy to treat epilepsy. Some
patients do not respond favorably to the AEDs treatment, resulting in pharmacoresistant epilepsy.

Conclusion:
Further to address the challenges faced in treating epilepsy, recent approaches like optogenetics,
chemogenetics, and genome editing, such as clustered regularly interspaced short palindromic
repeats (CRISPR), are emerging as target-specific therapeutic strategies.
Predictors of Impaired Left Ventricular Global Longitudinal Strain in Patients with Essential Hypertension and Preserved Ejection Fraction
Authors: Noori Ahmed A. , Barzani Mudhafar A. 
Published: December 2022

Background:
Early identification of hypertensive patients at risk of heart failure (HF) helps guide treatment intensification and predict prognosis. Global longitudinal strain (GLS) derived from two-dimensional speckle-tracking echocardiography (STE) uncovers subclinical left ventricular (LV) systolic dysfunction (SLVSD) in patients with hypertension (HT) and preserved LV ejection fraction (PLVEF). STE is unavailable and/or underutilized in our locality for financial and technical reasons.

Objectives:
We aim to identify clinical and echocardiographic parameters associated with and/or predictive of impaired GLS in hypertensive patients with PLVEF.

Method:
In this single-clinic, cross-sectional, observational study, 100 hypertensive patients with PLVEF were examined using conventional and 2D STE.

Results:
The average GLS was found to be mildly reduced (-18.4 ± 2.2%) in the study group. Lower GLS (than -19%) was more common among patients with poorly controlled HT (Odds Ratio (OR)=9), being on multiple anti-hypertensive agents (OR=5), positive Sokolow-Lyon electrocardiographic criteria (OR=4.3), and obesity (OR=2). Conventional echocardiographic parameters predicting impaired GLS included: mitral annular plane systolic excursion (MAPSE) (p=0.001), inter-ventricular septal thickness (IVSd) (p=0.003), LV mass (p=0.003), and LV remodelling (p=0.02). The aortic acceleration-to-ejection time ratio (AT/ET) had a good correlation with GLS (p=0.034). The novel product (IVSd x AT/ET) ≥2.7 mm was found to be the best predictor of GLS worse than -19% (AU ROC=0.8, 95% CI [0.68-0.93]; p=0.001).

Conclusion:
In hypertensive patients with PLVEF, GLS was found to correlate well with blood pressure (BP) control, body size, measures of LV mass, and MAPSE. These parameters predict at least 50% of the variance in GLS and could help practitioners with limited access to STE in risk-stratifying hypertensive patients.
D-allose: Molecular Pathways and Therapeutic Capacity in Cancer
Authors: Khajeh Sahar , Ganjavi Maryam , Panahi Ghodratollah , Zare Mina , Zare Mohammadreza , Tahami Seyed Mohammad , Razban Vahid 
Published: December 2022

Background:
Despite the implementation of various cancer therapies, adequate therapeutic
efficacy has not been achieved. A growing number of studies have been dedicated to the discovery of
new molecules to combat refractory cancer cells efficiently. Recently, the use of a rare type of sugar,
D-allose, has attracted the attention of research communities. In combination with the first-line treatment
of cancers, including different types of radiotherapies and chemotherapies, D-allose has been detected
with favorable complementary effects.

:
Understanding the mechanism of therapeutic target molecules will enable us to develop new strategies
for cancer patients that do not currently respond to the present therapies.

Objective:
We aimed to provide a review of the effects of D-allose in cancer treatment, its mechanisms
of action, and gaps in this field that require more investigations.

Discussion:
With rare exceptions, in many cancer types, including head and neck, lung, liver, bladder,
blood, and breast, D-allose consistently has exhibited anticancer activity in vitro and/or in vivo. Most
of the D-allose functions are mediated through thioredoxin-interacting protein molecules. D-allose exerts
its effects via reactive oxygen species regulation, cell cycle arrest, metabolic reprogramming, autophagy,
apoptosis induction, and sensitizing tumors to radiotherapy and chemotherapy.

Conclusion:
D-allose has shown great promise for combating tumor cells with no side effects, especially
in combination with first-line drugs; however, its potential for cancer therapy has not been comprehensively
investigated in vitro or in vivo.
Efficacious Restoration of Intractable Trauma by Administration of
Mesenchymal Stem/Stromal Cells and Hydrogel Composite: A Case Series
Authors: Zhang Leisheng , Han Zhongchao 
Published: December 2022

Background and Objectives:
Patients with intractable cutaneous injuries and complications
such as severe ulcers and dysfunctions often result in unfavorable prognosis and burdensome
possessions esthetically and psychosocially. This study aimed to evaluate the preliminary safety
and efficacy outcomes of hyaluronic acid/placenta-derived mesenchymal stem/stromal cells
(HA/P-MSCs) composite upon extensive traumas.

Methods:
The phase Ⅰ of the interventional study with four enrolled patients with refractory
wounds and ulcerations was conducted. With the consent of the patients and approval of the ethics
committee, continuous HA/P-MSC composite administration was conducted on the surface of
wounds after surgical debridement. The dynamic changes in pathomorphology and therapeutic response
were collectively recorded.

Results:
All the participants revealed efficacious remission with clinical-grade HA/P-MSC composite,
including complete wound healing, elimination of inflammatory exudate and refractory ulcers,
and regeneration of damaged tissues under sterile conditions. No untoward effects or recurrence
were observed in the cases during treatment and the 24-month’s follow-up visit.

Conclusion:
Refractory wound management with HA/P-MSC composite was preliminarily safe
and effective for the improvement of the outcomes of the patients. These findings provided new references
for the treatment of the costliest and incurable diseases associated with cutaneous injuries.

Clinical Trial Registration Number:
ChiCTR2000038275
Lithium-induced Discontinuation Refractoriness: A Report of
Two Cases
Authors: İnanlı İkbal 
Published: December 2022

Introduction:
Lithium is an effective mood stabilizer. In patients with bipolar disorder
using long-term lithium, discontinuation of lithium can lead to severe clinical outcomes
such as lithium-induced discontinuation refractoriness. We present two clinical cases of lithium-
induced discontinuation refractoriness.

Case Presentation:
We present two female patients with a good long-term response to lithium.
Both patients did not have a mood episode for many years and had residual symptoms. The
first patient discontinued lithium voluntarily, while the second patient discontinued lithium
treatment due to impaired thyroid function. Lithium was added to the treatment of both patients,
but lithium-induced discontinuation refractoriness developed.

Conclusion:
It should be kept in mind that it may develop refractoriness to lithium when deciding
to discontinue lithium treatment, especially in patients with a good long-term response to
lithium.
The Effect of Power on Nitrate Synthesis and The Emission Intensities of Reactive Species Using Anodic Plasma Electrolysis
Authors: Harianingsih Harianingsih , Saksono Nelson , Karamah Eva Fathul , Zakaria Zainal 
Published: December 2022

Nitrates are used as fertilizer to fulfill nutrients for plants. Anodic plasma electrolysis technology can be an effective and environmentally friendly solution in nitrogen fixation into nitrate compounds. This research aimed to determine the effect of controlling voltage and power in nitrate synthesis using plasma electrolysis with air as the raw material injected at the anode. The material used is an electrolyte solution of 0.02 M K2SO4, the electrodes used are in the form of tungsten and stainless steel, and a nitrate reagent is used for the nitrate test. The results of the study showed that at 400 W, the optimal rate was 0.8 L men-1 with 1889 mg L-1 of nitrate formed. While at 500 W and 600 W, the optimal rate of 1 L men-1 with nitrate formed was 2213 mg L-1 and 2453 mg L-1. The emission intensities of reactive species N, N2*, N2+,•OH, •H, and •O at an optimal rate of 0.8 L men-1 400 W 700 V in 20139 au, 28540 au, 18023 au, 30863 au, 12547 au, 49800 au. The addition of air injection will increase the oxygen input into the plasma zone, which can produce reactive species •O and nitrogen produces reactive species N, N2*, N2+ forms NO. The formed NO compounds can be oxidized to NO2, and the reaction between NO2 and reactive species •OH forms nitrates.