bluuebunny/crossref_metadata_2025_split huggingface dataset:
Left ventricular pressure strain loops for evaluation on myocardial work in type 2 diabetic patients with or without hypertension
Authors: HUANG Mei-feng , YUAN Xin-chun , ZENG Xi , ZHANG Zhe-yuan , XIA Qing-qing , ZHOU Zhi-yu 
Published: September 2022

Abstract
Purpose: To evaluate the myocardial work (MW) changes in type 2 diabetes mellitus (T2DM) patients with or without hypertension(HT) using left ventricular pressure strain loops（LVPSL）, and to find independent related factors of MW parameters.
Methods: 40 T2DM patients, 38 T2DM patients with HT and 35 controls were enrolled. The differences between clinical data, conventional ultrasound parameters and MW parameters were analyzed among the three groups.
Results: The global longitudinal strain (GLS) of T2DM group and T2DM+HT group was lower than controls (P＜0.05). The global work index (GWI) and global constructive work (GCW) in T2DM group were lower than other groups (P＜0.05). T2DM+HT group had higher global work waste (GWW) and lower global work efficiency (GWE) (P＜0.05). Systolic blood pressure (SBP), glycosylated hemoglobin (HbA1c), duration of D2DM and pulse pressure (PP) were independent related factors of GWI, while SBP, HbA1c, duration of T2DM and diastolic blood pressure (DBP) were GCW. SBP and HbA1c were independent factors of GWW, HbA1c and duration of HT were independent factors of GWE.
Conclusion: LVPSL can recognize left ventricular subclinical systolic dysfunction early in patients with T2DM. SBP and HbA1c are two factors that have a considerable impact on MW parameters. GWE may be the best predictor of the left ventricular systolic function in the MW parameters. The impact of afterload on MW parameters should be paid more attention.
Prevalence and antibiotic resistance profile of Salmonella spp. in broiler carcasses from dominant poultry production areas in Bhutan
Authors: Penjor Kinley , Gurung Monu , Islam Kamrul , Magalhaes Ricardo J. Soares 
Published: September 2022

Abstract
Background: Salmonella is an important zoonotic pathogen and its infections are considered among the most commonly and widely distributed food-borne illness reported worldwide. Poultry products have been identified as important sources of Salmonella infection to humans. While there have been reports of high prevalence of Salmonella and multidrug resistance in imported chicken meat in Bhutan, the safety of nationally produced broiler meat with regards to Salmonella contamination is not known. In the absence of national surveillance of Salmonella in food animals in Bhutan, this study assessed the prevalence of Salmonella and its serotypes in broiler chicken carcass in the dominant poultry production areas of the country and determine its antibiotic susceptibility patterns.
Methods: A cross-sectional study was conducted in January to April 2016 in all five major commercial broiler meat producers and suppliers in Bhutan located in the Samphelling and Darla gewogs. Following a systematic random sampling method, 36 broiler carcasses were sampled from each of the five broiler commercial farms producing the total sample size of 180 samples. Salmonella was isolated and identified following the International Organization for Standardization methods (ISO 6579:2002). All Salmonella isolates were subjected to antibiotic susceptibility testing (AST) following the procedures of the Clinical and Laboratory Standards Institute (CLSI) method.
Results: The overall prevalence of Salmonella in broiler chicken meat samples was 12.78% (95% CI, 10.98 – 14.58). The prevalence of Salmonella spp. was higher in farms of the Samphelling gewog compared to Darla gewog [14.81% (95% CI, 8.2.7 – 21.5) vs 9.72% (95% CI, 2.9 – 16.6) respectively]. Among 23 Salmonella isolates, the most prevalent serovar was Salmonella ser. Typhi (73.9%). The Salmonella isolates showed high sensitivity to gentamicin (73.9% of isolates) followed by streptomycin (56.5%) and ampicillin (47.8%). The highest proportion of resistance was noted to tetracycline (95.6%), trimethoprim (86.9%), amoxicillin (65.2%), and ampicillin (47.8%). Among 23 Salmonella isolates, 60.87% (n=14) were considered multidrug resistant and 7 patterns of multidrug resistance were discovered.
Conclusion: The estimates of Salmonella prevalence and multidrug resistance in nationally produced commercial broiler chicken carcasses from the two main broiler meat producing areas in Bhutan, raises significant public health concerns highlighting the need for an integrated national Salmonella surveillance program across the poultry market chain.
Discovery and Activity Evaluation of the Inhibitory Effect of Four Kinds
of Traditional Chinese Medicine Extracts on the CYP3A4 Enzyme
Authors: Ai Chenyang , Miao Xinxin , Wang Lili , He Jun 
Published: September 2022

Background and Objective:
Traditional Chinese medicines that have inhibitory effects
on the CYP3A4 enzymes were screened and their inhibitory effects were verified with in vitro bioassay.

Methods:
The computer virtual screening methods, including the CYP3A4 enzyme pharmacophore
model and the molecular docking method, were used to rapidly screen the potential CYP3A4 inhibitors
in the Traditional Chinese Medicine Database (TCMD), and then in vitro experiments were
conducted to validate the computational data.

Results:
A total of 413 chemical components in TCMD that have potential inhibitory effects on the
CYP3A4 enzyme were screened, and four kinds of traditional Chinese medicines (Abrus precatorius,
Andrographis paniculata, Angelica pubescens f.biserrata and Lithospermum erythrorhizon) contained
the most potential CYP3A4 inhibitors; The results of the in vitro experiments showed that
these four traditional Chinese medicine extracts all had certain degrees of inhibition on the CYP3A4
enzyme, with IC50 values of 5.15, 14.97, 15.2, and 24.21 μg/ml, respectively.

Conclusion:
The extracts of Abrus precatorius, Andrographis paniculata, Angelica pubescens f.
biserrata and Lithospermum erythrorhizon had certain inhibitory effects on the CYP3A4 enzyme,
and attention should be paid to the possible adverse reactions when they were used in combination
with the CYP3A4 enzyme-substrate drugs. A combination of computational approaches might be a
useful tool to identify potential inhibitors of the CYP3A4 enzyme from traditional Chinese medicine.
Therapeutic Peptides: Unravelling Conformational Dynamics by Systematic Application of Biophysical Techniques
Authors: Prabhu Arati , Pise Nikita , Raheja Radhika , Dhala Illham 
Published: September 2022

Abstract:
Peptide therapeutics represents one of the fastest-growing sectors in the pharmaceutical
drugs pipeline, with an increasing number of regulatory approvals every year. Their pharmacological
diversity, biocompatibility, high degree of potency and selectivity make them an attractive choice in
several therapeutic areas, such as diabetes, cancer, immune, metabolic, cardiovascular and infectious
diseases. However, the development of peptides as drugs presents its own set of challenges, necessitating
extensive property optimization aimed at improving their drug-like properties and stability in biological
environments. The discovery and development of innovative peptide therapeutic platforms entail
the employment of several biophysical techniques, which monitor the structural as well as the functional
integrity of peptides. Small structural changes of the bioactive peptides in response to the presence
of various excipients can have a major impact on their pharmaceutical prowess, necessitating the
use of analytical techniques for efficient quality control during development. Here we present some
widely used methods, such as circular dichroism, fluorescence spectroscopy and multi-dimensional
homo and heteronuclear nuclear magnetic resonance spectroscopy that form an integral part of therapeutic
peptides development. The application of combination biophysical platforms ensures the
maintenance of the appropriate folded structure, which is a prerequisite for the safety and efficacy of
peptide pharmaceuticals.
Gut Microbiome Alterations in Men Who Have Sex with Men-A Preliminary
Report
Authors: Zhang Zhihua , Lu Xiaoyan , Zhang Kexin , Wang Tianli , Zhang Xueqing , Zhang Jianghui , Wei Hongyuan , Gao Pan , Wang Jun , Zhang Hongbo 
Published: September 2022

Background:
Studies have found that HIV is mainly transmitted through the mucosal
surface, and the entrance of early progression of the disease is the rectal and colonic mucosa. So,
this paper aimed to explore and analyze the structural differences of gut microbiome between men
who have sex with men (MSM) and those who don’t have sex with men (Non-MSM), expecting to
find novel biological factors that potentially impact transmission and/or disease in MSM population.

Methods:
We collected a total of 33 stool samples, 16 were MSM and 17 were Non-MSM. The 16S
rRNA gene amplification sequencing was used to detect the alteration and structure of the gut microbiome
community in two groups.

Results:
The difference in β diversity of gut microbiome of two groups of subjects was statistically
significant (P<0.001), indicating that the difference in the structure of the gut microbiome of two
groups was statistically significant. Compared with the phylum and genus level of Non-MSM
group, the relative abundances of Actinobacteria, Proteobacteria, genera Collinsella, Prevotella,
Bifidobacterium and Ralstonia in MSM group were higher (P<0.001, P<0.05, LDA score
(log10)>2), and the relative abundance of Bacteroidetes, genera Erysipelotrichaceae incertae sedis,
Bilophila, Holdemania, Clostridium XIVb and Bacteroidaceae in MSM group were lower (P<0.01,
LDA score (log10)>2).

Conclusions:
There are some differences in the structure of gut microbiome between MSM group
and Non-MSM group. It indicates the differences in behavior and characteristics between MSM and
Non-MSM populations may be related to the difference in the structure of gut microbiome.
The Nonlinear Optical Properties of Ferrocene-containing Metalloporphyrins
Toward the Pico-second Laser
Authors: Guo Fengqi , Wang Yue , Huang Xuewei , Qian Xiaodie , Lu Yinjie , Chen Zongwei 
Published: September 2022

Background:
The nonlinear optical properties of ferrocene-containing metalloporphyrins
toward pico-second laser were studied using calculational and experimental methods, and the relationship
between their structures and nonlinear absorption properties were discussed.

Aims:
The metal ions introduced into the porphyrin rings intensively affect the nonlinear optical properties.

Methods:
The nonlinear optical properties and the relationship between the property and the structure
of the synthesized ferrocene-containing metalloporphyrins are studied using the calculational method
and the open-aperture Z-scan technology for pico-second laser.

Results:
The Z-scan results show that Co-P-Fc, Zn-P-Fc and Pd-P-Fc exhibit reverse saturable absorption
characteristics toward the laser with 532 nm wavelength and 21 ps pulse width, and the nonlinear
absorption coefficients (β) of them were 4.1, 3.2 and 1.3 cm/GW, respectively, when the incident laser
fluency at the focal point of the lens is 29 mJ/cm2. In addition, the values of β decrease with the increase
of the incident laser fluency. These results indicate that the nonlinear absorption characteristics
of Co-P-Fc, Zn-P-Fc and Pd-P-Fc are ascribed to the excited state absorption (ESA). However, Cu-PFc,
Ni-P-Fc and P-Fc show saturated absorption characteristics toward the ps laser pulse.

Conclusion:
To elucidate the intrinsic factors that influence the nonlinear optical properties, the electronic
distribution, flow of charge density during the transition from the ground state to the excited
state, and the first-order hyperpolarizability values (β) are calculated using the time-dependent density
functional theory (TD-DFT). The calculated results show that the molecular polarity and the change of
the molecular polarity before and after the transition from HOMO to LUMO, which is dominated by
the redox potentials of the introduced metal ions, are the most important factors that affect the nonlinear
optical properties of the title compounds.
Synthesis, Characterization and Biological Activity of Benzimidazoleacrylonitrile
Derivatives
Authors: Parveen Mehtab , Azeem Mohammad , Aslam Afroz , Haris Mohammad , Khan Amir , Alam Mahboob 
Published: September 2022

Background:
Benzimidazoles have a wide range of synthetic applications in medicinal
chemistry and biological activities like anti-tumor/anti-proliferative activities etc. Moreover, different
heterocyclic moieties attached to the benzimidazole ring improved anticancer activities.

Methods:
All the chemicals were purchased from Aldrich Chemical Company, are of AR grade
and used as received. Microanalytical data (C, H, and N) were analyzed on a Carlo Erba model
1108 analyzer. Melting points were measured by the Kofler apparatus and were uncorrected. Spectroscopic
data were obtained using the following instruments: Fourier transform infrared spectra
(KBr discs, 4000-400 cm-1) by Shimadzu IR-408 Perkin Elmer 1800 instrument; 1H NMR and 13C
NMR spectra by JEOL Resonance Inc. Tokyo, Japan, JNM-ECZ400S/L1 using DMSO-d6 as a
solvent containing TMS as the internal standard. Chemical shifts (δ) are reported in parts per million
(ppm), and coupling constants (J) are reported in Hertz (Hz).

Results:
We chose sulfosalicylic acid as a promoter for forming benzimidazole-acrylonitrile derivatives,
which is an eco-friendly reaction, and we applied a series of synthesized compounds 3a-g
in nematicidal activity. The results indicate that the concentrations of all treatments significantly
kill M. incognita.

Conclusion:
This model reaction procedure provides a better method for preparing benzimidazoleacrylonitrile,
which is superior to other methods. This protocol simplifies handling model reactions
with mild reaction conditions, a short time period, a simple set-up, a fast reaction rate, and so on.
Quantum Mechanics Modeling of Oxetanes as Epoxide Hydrolase Substrates
Authors: Di Li , Tu Meihua , Ngo Jackson 
Published: September 2022

Background:
Epoxide hydrolases comprise an important class of enzymes that have critical functions in the detoxification of xenobiotics and regulation of signaling molecules. In addition to epoxides, oxetanes have recently been identified as novel substrates of microsomal epoxide hydrolase (mEH). Oxetanes are common scaffolds used in medicinal chemistry design to improve potency and drug-like properties. Metabolism of oxetanes by mEH can result in high uncertainties in the prediction of human clearance due to extrahepatic contribution and large interindividual variability. Therefore, reducing mEH-mediated oxetane metabolism is highly desirable to minimize its contribution to clearance.

Objective:
The aim of the study is to evaluate whether quantum mechanical parameters are able to predict the hydrolytic rate of mEH-mediated oxetane metabolism in order to guide medicinal chemistry design in order to minimize mEH contribution to clearance.

Methods:
Quantum mechanics modeling was used to evaluate the hydrolytic rate of twenty-three oxetanes by mEH. All modeling studies were performed with the Maestro software package.

Results:
The results show that LUMO energy is highly correlated with the diol formation rate of oxetane hydrolysis by mEH for compounds that are structurally similar, while other quantum mechanical parameters are less predictive. The data suggest that the intrinsic reactivity determines the hydrolytic rate of oxetanes. This occurs when the orientations of the molecules in the mEH active site are similar. Predictions of mEH substrate metabolic rates using LUMO are most accurate when comparing subtle structural changes without drastic changes in MW and chemotype.

Conclusion:
The study suggests that LUMO energy can be used to rank-order oxetanes for their hydrolytic rate by mEH for structurally similar compounds. This finding enables the medicinal chemistry design to reduce mEH-mediated oxetane metabolism based on the calculated LUMO energy.
Trifluoromethylated Aryl Sulfonamides as Novel CETP Inhibitors:
Synthesis, Induced Fit Docking, Pharmacophore Mapping and Subsequent
In vitro Validation
Authors: Khalaf Reema Abu , Shaiah Hamza Al , Sabbah Dima 
Published: September 2022

Background:
Cardiovascular disease is one of the leading causes of death. Atherosclerosis
causes arterial constriction or obstruction, resulting in acute cardiovascular illness. Cholesteryl ester
transfer protein (CETP) facilitates reverse cholesterol transport. It supports the transfer of cholesteryl
ester from HDL to LDL and VLDL. Inhibition of CETP by drugs limits cardiovascular disease by
decreasing LDL and increasing HDL.

Objectives:
In this study, fourteen trifluoromethyl substituted benzene sulfonamides 6a-6g and 7a-7g
were prepared.

Methods:
The synthesized molecules were characterized using 1H-NMR, 13C-NMR, IR and HR-MS.
They were in vitro tested to estimate their CETP inhibitory activity.

Results:
In vitro biological evaluation showed that compounds 7d-7f had the highest inhibitory activity
with 100% inhibition, while the inhibition observed by compounds 6a-6g, 7a-7c and 7g ranged
from 2%-72% at 10 μM concentration. It was found that the addition of a fourth aromatic ring
significantly improved the activity, which may be due to the hydrophobic nature of CETP. Also, the
presence of ortho-chloro, meta-chloro and para-methyl substituents results in high inhibitory activity.

Conclusion:
The induced fit docking studies revealed that hydrophobic interaction guided ligand/
CETP binding interaction in addition to H-bond formation with Q199, R201, and H232. Furthermore,
pharmacophore mapping demonstrated that this series satisfies the functionalities of the current
CETP inhibitors.
Computational Evidence Based Perspective on the Plausible Repositioning
of Fluoroquinolones for COVID-19 Treatment
Authors: Yadav Vikas 
Published: September 2022

Abstract:
The coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a serious global healthcare crisis, so there is an emergence of identifying efficacious therapeutic options. In a setting where there is an unavailability of definitive medication along with the constant eruption of vaccine-related controversies, the drug-repositioning approach seems to be an ideal step for the management of COVID-19 patients. Fluoroquinolones (FQs) are commonly prescribed antibiotics for the treatment of genitourinary tract and upper respiratory tract infections, including severe community-acquired pneumonia. Research over the years has postulated multifaceted implications of FQs in various pathological conditions. Previously, it has been reported that few, but not all FQs, possess strong antiviral activity with an unknown mechanism of action. Herein, an interesting perspective is discussed on repositioning possibilities of FQs for the SARS-CoV-2 infections based on the recent in silico evidential support. Noteworthy, FQs possess immunomodulatory and bactericidal activity which could be valuable for patients dealing with COVID-19 related complications. Conclusively, the current perspective could pave the way to initiate pre-clinical testing of FQs against several strains of SARS-CoV-2.
Insulin Resistance and Diabetes Mellitus in Patients with Systemic Lupus
Erythematosus
Authors: García-Carrasco Mario , Mendoza-Pinto Claudia , Munguía-Realpozo Pamela , Etchegaray-Morales Ivet , Vélez-Pelcastre Sandra Karina , Méndez-Martínez Socorro , Zamora-Ginez Irma , de Lara Luis Guillermo Vázquez , Gálvez-Romero José Luis , Escamilla-Márquez Marco 
Published: September 2022

Abstract:
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized
by damage to multiple systems and a higher risk of cardiovascular disease. In addition,
several studies have found that insulin resistance (IR) is more prevalent in SLE patients
than controls, increasing the risk of prediabetes, type 2 diabetes mellitus (T2DM) and
morbidity. The objective of this review was to summarize the most relevant evidence
about the relationship among IR, T2DM and SLE, including the effects of pro-inflammatory
states, acute-phase proteins, pro-inflammatory cytokines, and pharmacological SLE
treatment. A better understanding of the mechanisms involved in these comorbidities will
allow better treatment strategies.
An Economic Impact Model for Estimating the Value to Health Systems of a Digital Intervention for Diabetes Primary Care: Development and Usefulness Study
Authors: Powers Brenton , Bucher Amy 
Published: September 2022

Background
Diabetes is associated with significant long-term costs for both patients and health systems. Regular primary care visits aligned with American Diabetes Association guidelines could help mitigate those costs while generating near-term revenue for health systems. Digital interventions prompting primary care visits among unengaged patients could provide significant economic value back to the health system as well as individual patients, but only few economic models have been put forth to understand this value.

Objective
Our objective is to establish a data-based method to estimate the economic impact to a health system of interventions promoting primary care visits for people with diabetes who have been historically unengaged with their care. The model was built with a focus on a specific digital health intervention, Precision Nudging, but can be used to quantify the value of other interventions driving primary care usage among patients with diabetes.

Methods
We developed an economic model to estimate the financial value of a primary care visit of a patient with diabetes to the health system. This model requires segmenting patients with diabetes according to their level of blood sugar control as measured by their most recent hemoglobin A1c value to understand how frequently they should be visiting a primary care provider. The model also accounts for the payer mix among the population with diabetes, documenting the percentage of insurance coverage through a commercial plan, Medicare, or Medicaid, as these influence the reimbursement rates for the services. Then, the model takes into consideration the population base rates of comorbid conditions for patients with diabetes and the associated current procedural terminology codes to understand what a provider can bill as well as the expected inpatient revenue from a subset of patients likely to require hospitalization based on the national hospitalization rates for people with diabetes. Physician reimbursement is subtracted from the total. Finally, the model also accounts for the level of patient engagement with the intervention to ensure a realistic estimate of the impact.

Results
We present a model to prospectively estimate the economic impact of a digital health intervention to encourage patients with documented diabetes diagnoses to attend primary care visits. The model leverages both publicly available and health system data to calculate the per appointment value (revenue) to the health system. The model offers a method to understand and test the financial impact of Precision Nudging or other primary care–focused diabetes interventions inclusive of costs driven by comorbid conditions.

Conclusions
The proposed economic model can help health systems understand and evaluate the estimated economic benefits of interventions focused on primary care and prevention for patients with diabetes as well as help intervention developers determine pricing for their product.