bluuebunny/crossref_metadata_2025_split huggingface dataset:
Random-Forest-Algorithm-Based Applications of the Basic Characteristics
and Serum and Imaging Biomarkers to Diagnose Mild Cognitive Impairment
Authors: Yang Juan , Sui Haijing , Jiao Ronghong , Zhang Min , Zhao Xiaohui , Wang Lingling , Deng Wenping , Liu Xueyuan 
Published: January 2022

Background:
Mild cognitive impairment (MCI) is considered a s the early stage of Alzheimer's Disease (AD). The purpose of our study was to analyze the basic characteristics andserum and imaging biomarkers for the diagnosis of MCI patients as a more objective and accurate approach.

Methods:
The Montreal Cognitive Test was used to test 119 patients aged ≥65. Such serum bio-markers were detected as preprandial blood glucose, triglyceride, total cholesterol, Aβ1-40, Aβ1-42, and P-tau. All the subjects were scanned with 1.5T MRI (GE Healthcare, WI, USA) to obtain DWI, DTI, and ASL images. DTI was used to calculate the anisotropy fraction (FA), DWI was used to calculate the apparent diffusion coefficient (ADC), and ASL was used to calculate the cerebral blood flow (CBF). All the images were then registered to the SPACE of the Montreal Neurological Institute (MNI). In 116 brain regions, the medians of FA, ADC, and CBF were extracted by automatic anatomical labeling. The basic characteristics included gender, education level, and previous disease history of hypertension, diabetes, and coronary heart disease. The data were randomly divided into training sets and test ones. The recursive random forest algorithm was applied to the diagnosis of MCI patients, and the recursive feature elimination (RFE) method was used to screen the significant basic features and serum and imaging biomarkers. The overall accuracy, sensitivity, and specificity were calculated, respectively, and so were the ROC curve and the area under the curve (AUC) of the test set.

Results:
When the variable of the MCI diagnostic model was an imaging biomarker, the training accuracy of the random forest was 100%, the correct rate of the test was 86.23%, the sensitivity was 78.26%, and the specificity was 100%. When combining the basic characteristics, the serum and imaging biomarkers as variables of the MCI diagnostic model, the training accuracy of the random forest was found to be 100%; the test accuracy was 97.23%, the sensitivity was 94.44%, and the specificity was 100%. RFE analysis showed that age, Aβ1-40, and cerebellum_4_6 were the most important basic feature, serum biomarker, imaging biomarker, respectively.

Conclusion:
Imaging biomarkers can effectively diagnose MCI. The diagnostic capacity of the basic trait biomarkers or serum biomarkers for MCI is limited, but their combination with imaging biomarkers can improve the diagnostic capacity, as indicated by the sensitivity of 94.44% and the specificity of 100% in our model. As a machine learning method, a random forest can help diagnose MCI effectively while screening important influencing factors.
Preparation of Modified Chitosan-based Nanoparticles for Efficient
Delivery of Doxorubicin and/or Cisplatin to Breast Cancer Cells
Authors: Matalqah Sina M. , Aiedeh Khalid , Mhaidat Nizar M. , Alzoubi Karem H. , AL-Husein Belal A. 
Published: January 2022

Purpose:
The aim is to develop a novel pH-responsive modified chitosan-based nanoparticles
system for active loading of doxorubicin (DOX) and triggered intracellular release.

Methods:
Nanoparticles were formed in an aqueous medium via ionic interaction between negatively
charged chitosan derivative and positively charged DOX at neutral pH and then transformed in situ
into cisplatin (CIS) cross-linked nanoparticles through cross-linking the formed micelles via chelation
interaction between the negatively charged polymeric carrier and cisplatin. Nanoparticles were characterized
in terms of particle size and zeta potential using DLS and TEM. Drug loading efficiency and
encapsulation efficiency were determined based on the physio-chemical proprieties of the polymer and
the amount of the cross-linking agent. In vitro release studies were performed using the dialysis method
at different pHs. Finally, the cytotoxic effects of these nanoparticles were performed against the
MCF-7 BrCA cell line under different pHs.

Results:
The average particle size of polymer alone and DOX nanoparticles was 277.401 ± 13.50 nm
and 290.20 ± 17.43 nm, respectively. The zeta potential was -14.6 ± 1.02 mV and -13.2 ± 0.55 mV,
respectively, with a low polydispersity index. Drug loading and encapsulation deficiencies were determined,
dependent on the amount of the cross-linking agent. In vitro release studies showed that the
release of DOX from these nanoparticles was pH-dependent. Moreover, results showed that the cytotoxicity
magnitude of DOX-loaded nanoparticles against MCF-7 BrCA cells was higher compared
with free DOX.

Conclusion:
These novel pH-sensitive nanoparticles proved to be a promising Nano-drug delivery for
tumor-targeted delivery of DOX.
Protein Tyrosine Phosphatase 1B (PTP1B): Insights into its New Implications
in Tumorigenesis
Authors: Chen Pei-Jie , Zhang Yun-Tian 
Published: January 2022

Abstract:
In vivo, tyrosine phosphorylation is a reversible and dynamic process governed by the opposing
activities of protein tyrosine kinases and phosphatases. Defective or inappropriate operation
of these proteins leads to aberrant tyrosine phosphorylation, which contributes to the development of
many human diseases, including cancers. PTP1B, a non-transmembrane phosphatase, is generally
considered a negative regulator of the metabolic signaling pathways and a promising drug target for
type II diabetes and obesity. Recently, PTP1B is gaining considerable interest due to its important
function and therapeutic potential in other diseases. An increasing number of studies have indicated
that PTP1B plays a vital role in the initiation and progression of cancers and could be a target for
new cancer therapies. Following recent advances in the aspects mentioned above, this review is focused
on the major functions of PTP1B in different types of cancer and the underlying mechanisms
behind these functions, as well as the potential pharmacological effects of PTP1B inhibitors in cancer
therapy.
Multi-target Approaches of Epigallocatechin-3-O-gallate (EGCG) and its
Derivatives against Influenza Viruses
Authors: da Silva-Júnior Edeildo Ferreira , Silva Leandro Rocha 
Published: January 2022

Abstract:
Influenza viruses (INFV), the Orthomyxoviridae family, are mainly transmitted among
humans via aerosols or droplets from the respiratory secretions. However, fomites could be a potential
transmission pathway. Annually, seasonal INFV infections account for 290-650 thousand
deaths worldwide. Currently, there are two classes of approved drugs to treat INFV infections, being
neuraminidase (NA) inhibitors and blockers of matrix-2 (M2) ion channel. However, cases of
resistance have been observed for both chemical classes, reducing the efficacy of treatment. The
emergence of influenza outbreaks and pandemics calls for new antiviral molecules that are more effective,
and that could overcome the current resistance to anti-influenza drugs. In this context, polyphenolic
compounds are found in various plants, and these have displayed different multi-target
approaches against diverse pathogens. Among these, green tea (Camellia sinensis) catechins, in special
epigallocatechin-3-O-gallate (EGCG), have demonstrated significant activities against the two
most relevant human INFV, subtypes A and lineages B. In this sense, EGCG has been found to be
a promising multi-target agent against INFV since it can act inhibiting NA, hemagglutination
(HA), RNA-dependent RNA polymerase (RdRp), and viral entry/adsorption. In general, the lack of
knowledge about potential multi-target natural products prevents an adequate exploration of them,
increasing the time for developing multi-target drugs. Then, this review aimed to compile most relevant
studies showing the anti-INFV effects of EGCG and its derivatives, which could become antiviral
drug prototypes in the future.
Computational Screening for Finding New Potent COX-2 Inhibitors as
Anticancer Agents
Authors: Verma Saurabh , Sahu Ankita , Pradhan Dibyabhaba , Raza Khalid , Qazi Sahar , Jain Arun Kumar 
Published: January 2022

Background:
Breast cancer ranks first in women and the second most common type of cancer overall. It is the most important barrier to the rise of life expectancy, globally affecting disease modalities. Cyclooxygenase-2 (COX-2) has become a prominent hallmark as inhibition target for breast cancer, and this therapeutic target for anti-inflammatory drugs regulates cell proliferation, angiogenesis, tumor growth and apoptosis. There is a need to explore new anti-cancerous drugs for searching the best possible hit candidates for cancer treatment. The computer-aided drug design approach was conducted to discover the new alternative COX-2 inhibitors.

Objective:
The research framework of this study is to identify new potent inhibitors for the COX-2 using computer-aided drug design.

Methods:
In the present investigation, an in-silico approach was used to screen with the best established three biological databases (Zinc15, ChemSpider and BindingDB) and docked against the COX-2 protein structure (PDB ID: 5IKR). Molecular docking was carried out using the Schrodinger Maestro suite. The compounds were filtered out based on their physicochemical, ADMET, and other drug-like properties. Several computational approaches such as molecular docking, binding free energy calculation, ADMET analysis, protein-ligand interaction and MD simulation were performed to determine the suitability of correct ligands for selected COX-2 target.

Results:
The two ligands showed relatively better binding affinities (-10.028 kcal/mol for compound A and -10.007 kcal/mol for ZINC000048442590) than the standard (-9.751 kcal/mol). These compounds followed Lipinski’s rule and drug-likeness index, which exhibited a good predicted therapeutic druggability profile. The interaction of the protein-ligand complex correlates with the COX-2. The MD simulation of the protein-ligand complex showed good stability in the time period of 10ns.

Conclusion:
It is the first study in which two new compounds ZINC000048442590 and compound A were found to be highly promising and have active potential in inhibiting cyclooxygenase-2 enzyme and could be effective as the potential drug candidates for breast cancer against COX-2 protein. Hopefully, in the future, these compounds as anti-inflammatory drug molecules could be used as new templates for the development of anticancer agents.
Bioisosterism in Drug Discovery and Development - An Overview
Authors: Jayashree B.S. , Nikhil P. Sai , Paul Soumyajeet 
Published: January 2022

Abstract:
Bioisosterism is a unique approach used by medicinal chemists for the reasonable modification
of lead compounds into safer, more clinically effective, economical, and therapeutically attractive
drugs. It is one of the most crucial lead modification tools, widely applied in the field of rational
drug design to amplify the desired activity and eliminate undesirable properties, thus facilitating the
optimization of pharmacokinetic profile and achievement of target selectivity. This review demonstrates
the importance of bioisosterism in the process of drug discovery and development and highlights
its relevance in the molecular evolution of many classes of drugs such as antibacterial sulfonamides,
anticancer drugs, antivirals, antifungals, anthelmintics, local anesthetics, barbiturates, antidepressants,
antihistamines, proton pump inhibitors and work carried out by our team of researchers.
The role of bioisosterism as a strategy to achieve inhibition of enzymes such as thymidylate synthase,
DNA polymerase, reverse transcriptase and several others has also been pointed out. There are no
limits to the classes of drugs where bioisosterism has been successfully applied.
Platycodon D-induced A549 Cell Apoptosis through RRM1-Regulated p53/VEGF/
MMP2 Pathway
Authors: Li Jiurong , Ma Aiping , Lan Wenbin , Liu Qun 
Published: January 2022

Background:
Lung cancer is one of the leading causes of cancer-related deaths worldwide. Platycodin D
(PD), a major pharmacological constituent from the Chinese medicinal herb named Platycodonis Radix, has shown
potent anti-tumor activity. Also, it is reported that PD could inhibit cellular growth in the non-small-cell lung carcinoma
(NSCLC) A549 cell line. However, the underlying mechanism is not fully clarified.

Methods:
Cell proliferation was measured by MTT assay. Annexin V and propidium iodide (PI) assay were employed
to study the apoptosis effects of PD on A549 cells. Western blot analysis was used to evaluate protein expression.
Also, we used a siRNA against p53, as well as a plasmid-based RRM1 over-expression to investigate their functions.

Results:
It is demonstrated that PD inhibited A549 cell proliferation in a dose- and time-dependent manner. Further
investigations showed that PD induced cell apoptosis, which was supported by dose-dependent and time-dependent
caspase-3 activation and p53/VEGF/MMP2 pathway regulation. Also, PD demonstrated the inhibition effect of ribonucleotide
reductase M1 (RRM1), whose role in various tumors is contradictory. Remarkably, in this work, RRM1 overexpression
in A549 cells could have a negative impact on the regulation of the p53/VEGF/MMP2 pathway induced by
PD treatment. Note that RRM1 overexpression also attenuated cell apoptosis and inhibition of cell proliferation of
A549 treated with PD.

Conclusion:
The results suggested that PD could inhibit A549 cell proliferation and induce cell apoptosis by regulating
p53/VEGF/MMP2 pathway, in which RRM1 plays an important role directly.
Designing a Sequence-Based Method for Identifying 14 High-Risk
Carcinogenic HPV Types in Multiple Infections
Authors: Alimardani Arezou , Dastmalchi Narges , Rahimi Hamzeh , Safaralizadeh Reza 
Published: January 2022

Background:
HPV tests have significant drawbacks in terms of detecting and differentiating
types of the virus. PCR techniques provide timely and necessary results for patient care with high quality,
sensitivity, and reasonable cost.

Methods:
The sensitivity of PCR depends on the primers. In this study, a method was designed that
exploited PCR with designed primers (ScTd) by changing the annealing temperature (Ta) along with
Sanger sequencing for pap smear samples. Sanger sequencing has confirmed that ScTd primers have a
relative differentiation power using PCR. The primers caused a relative differentiation by PCR. In the
pap smear sample 22 with contamination of types 16, 31, and 45, confirmed by dot blot hybridization,
type 16 was not amplified at the specific Ta. Moreover, the band was observed at low Ta.

Results:
Sanger sequencing showed that type 16 was detected instead of type 52. Sequencing the heterozygous
bands in multiple infections also led to the identification of different types. Moreover, with
a combination of 7 pairs of primers, HPV types can be detected in multiple infections by PCR.

Conclusions:
As compared with the clinical dot blot hybridization technique, the utilization of complementary
PCR and sequencing methods with designed primers can provide a higher positive predictive
value in the detection of high-risk types.
Влияние смещения периферического фрагмента пяточной кости при ее переломе на функцию трехглавой мышцы голени
Authors: Lazarev I.A. , Riabokon P.V. , Haller M. , Dendorfer S. 
Published: January 2022

В структуре повреждений опорно-двигательного аппарата переломы пяточной кости составляют до 4 % всех переломов скелета и до 60 % переломов заднего отдела стопы. Изучено влияние смещения периферического отломка пяточной кости на силы реакции мышц голени в момент принятия упрощенного положения приседа на корточки методом моделирования в программной среде AnyBody Modeling System 6.0. M.gastrocnemius (lateralis et medialis) в начальной фазе движения во всех вариантах смещения периферического фрагмента не развивала достаточных мышечных усилий по сравнению с интактной пяточной костью. M.soleus medialis et lateralis демонстрировала значительное повышение показателей мышечной активности в начальной фазе движения (41,87 ± 1,90 Н и 52,07 ± 2,10 Н) до достижения своих максимальных значений по сравнению с аналогичными показателями интактной пяточной кости. В конечной фазе движения, в момент достижения мышцей своей максимальной длины показатели мышечных сил m.soleus возвращались к исходным величинам или были значительно ниже этих значений. Снижение показателей мышечных сил происходило в связи с уменьшением плеча силы или мышечной экскурсии при сближении точек прикрепления мышцы. При смещении периферического фрагмента, за счет опускания пятки на поверхность опоры в условиях анатомического удлинения мышцы, ей требуется дополнительное усилие для достижения длины покоя и своего силового максимума. Во всех вариантах смещения периферического фрагмента нарушается функция трехглавой мышцы голени с вовлечением дополнительных мышечных усилий и энерготрат. Данный факт должен нацелить хирурга на необходимость точной репозиции отломков при переломе пяточной кости со смещением периферического фрагмента.
Нормативні показники якості та мінеральної щільності кісткової тканини на рівні поперекового відділу хребта в українських жінок різного віку
Authors: Povorozniuk V.V. , Dzerovych N.I. , Musiienko A.S. 
Published: January 2022

Метою дослідження було оцінити показники якості трабекулярної кісткової тканини (TBS) і мінеральної щільності кісткової тканини (МЩКТ) на рівні поперекового відділу хребта в українських практично здорових жінок різного віку. На базі Українського науково-медичного центру проблем остеопорозу обстежено 497 практично здорових жінок віком від 20 до 89 років, які були розподілені на сім груп за десятиріччями. У дослідження не включали жінок із мінеральною щільністю кісткової тканини на рівні поперекового відділу хребта та шийки стегнової кістки зі значенням Z-критерія за межами ±2 SD, із ранньою менопаузою (до 45 років), із ожирінням (індекс маси тіла > 30 кг/м2), з наявністю захворювань, що впливають на метаболізм кісткової тканини. МЩКТ на рівні поперекового відділу хребта (L1–L4) оцінювали за допомогою приладу двохенергетичної рентгенівської денситометрії (Prodigy, GE Lunar, Мадісон, США). Показник TBS (L1–L4) визначали за допомогою методики TBS iNsight (Med-Imaps, Pessac, Франція). У результаті проведеного дослідження встановлено, що максимальні значення показника TBS (L1–L4) та МЩКТ на рівні поперекового відділу хребта (L1–L4) визначені у жінок вікової групи 30–39 років. Вірогідно нижчий показник TBS (L1–L4) порівняно з жінками вікової групи 30–39 років встановлено у вікових групах 50–59, 60–69, 70–79 та 80–89 років, МЩКТ на рівні поперекового відділу хребта (L1–L4) — у вікових групах 40–49, 50–59, 60–69, 70–79 та 80–89 років. Зниження показника TBS (L1–L4) вірогідно збільшувалось з віком — від –3,11 % у віковій групі 40–49 років до –18,68 % — у віковій групі 80–89 років. Найбільш низькі показники МЩКТ на рівні поперекового відділу хребта (L1–L4) спостерігались у віковій групі обстежених жінок 40–49 років — –16,97 %. При цьому у віковій групі 80–89 років показник МЩКТ становив –9,50 %. Виявлені зміни МЩКТ обумовлені розвитком дегенеративно-дистрофічних змін на рівні хребта з віком. Таким чином, вагомість детермінант, що визначають міцність кісткової тканини, є відмінною у різних вікових періодах. Отримані нами результати підтверджують незалежність показника TBS у визначенні структурно-функціонального стану кісткової тканини та ризику остеопоротичних переломів. Встановлено негативний регресійний зв’язок між тривалістю постменопаузального періоду жінки та показником TBS. При проведенні регресійного аналізу між показниками якості та мінеральної щільності кісткової тканини на рівні поперекового відділу хребта (L1–L4) у загальній групі виявлено вірогідний позитивний зв’язок (p = 0,0001). При вивченні регресійного зв’язку у різних вікових групах вірогідна залежність виявлена тільки в обстежених жінок вікової групи 30–39 років. Враховуючи отримані нами результати, вважаємо, що при оцінці структурно-функціонального стану кісткової тканини та визначенні ризику переломів у кожний віковий період має бути індивідуальний підхід до пацієнта.
Наш опыт оперативного лечения внутрисуставных компрессионных переломов пяточной кости
Authors: Kolesnikov A.M. 
Published: January 2022

Цель работы: оценить результаты оперативного лечения пострадавших с внутрисуставными компрессионными переломами пяточных костей.Материалы и методы. Был проведен анализ оперативного лечения 35 больных, которые находились под нашим наблюдением за период с 2008 по 2012 год.Результаты. Результаты оценивались по шкале Maryland Foot Score через 3, 6, 12 мес. Через 3 месяца у 30 (85,7 %) больных были достигнуты удовлетворительные результаты и у 5 (14,3 %) — хорошие; через 6 месяцев у всех пациентов достигнуты хорошие результаты, через 12 — хорошие результаты сохранялись у 19 (54,3 %) больных, отличные результаты получены у 16 (45,7 %).Выводы. Основной задачей оперативного лечения должно являться восстановление конгруэнтности суставных поверхностей в подтаранном суставе, для чего в большинстве случаев необходимо замещение дефекта губчатой ткани.