bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dihydrofolate Reductase (DHFR) Inhibitors: A Comprehensive
Review
Authors: Sehrawat Renu , Rathee Priyanka , Khatkar Sarita , Akkol EsraKüpeli , Khayatkashani Maryam , Nabavi Seyed Mohammad , Khatkar Anurag 
Published: March 2023

Background:
Dihydrofolate reductase (DHFR) is an indispensable enzyme required
for the survival of most prokaryotic and eukaryotic cells as it is involved in the biosynthesis
of essential cellular components. DHFR has attracted a lot of attention as a molecular
target for various diseases like cancer, bacterial infection, malaria, tuberculosis, dental caries,
trypanosomiasis, leishmaniasis, fungal infection, influenza, Buruli ulcer, and respiratory illness.
Various teams of researchers have reported different DHFR inhibitors to explore their
therapeutic efficacy. Despite all the progress made, there is a strong need to find more novel
leading structures, which may be used as better and safe DHFR inhibitors, especially against
the microorganisms which are resistant to the developed drug candidates.

Objective:
This review aims to pay attention to recent development, particularly made in the
past two decades and published in this field, and pay particular attention to promising DHFR
inhibitors. Hence, an attempt has been made in this article to highlight the structure of dihydrofolate
reductase, the mechanism of action of DHFR inhibitors, most recently reported DHFR
inhibitors, diverse pharmacological applications of DHFR inhibitors, reported in-silico
study data and recent patents based on DHFR inhibitors to comprehensively portray the current
scenery for researchers interested in designing novel DHFR inhibitors.

Conclusion:
A critical review of recent studies revealed that most novel DHFR inhibitor compounds
either synthetically or naturally derived are characterized by the presence of heterocyclic
moieties in their structure. Non-classical antifolates like trimethoprim, pyrimethamine,
and proguanil are considered excellent templates to design novel DHFR inhibitors, and most
of them have substituted 2,4-diamino pyrimidine motifs. Targeting DHFR has massive potential
to be investigated for newer therapeutic possibilities to treat various diseases of clinical
importance.
Effectiveness of Aspartame on Insulin, Triglycerides, and Blood Glucose Concentration in Adult Type 2 Diabetic Patients
Authors: Ali Deeb Ammar Salim , Al-Qudah Maisa Muhammad Amin , Abu-Harirah Hashem Ahmad , El-Qudah Jafar Muhammad. , Abdelrahim Dana , Altaleb Hala Mashhour , Shoubaki Lana Salman 
Published: March 2023

Background:
Human beings have an attraction to sweet items: desserts, fruits, honey,
etc., which stimulate the sense of taste. However, sweet things tend to have many calories, thus
contributing to issues with obesity. Moreover, those with diabetes must strictly limit their consumption
of sugar to maintain their blood glucose levels within acceptable limits. Artificial
sweeteners contain substances from several distinct chemical classes. The effects of artificial
sweeteners on clinically relevant outcomes such as insulin, blood glucose, and lipids have been
incompletely studied.

Objective:
This study aims to assess the effects of artificial sweeteners on blood glucose, triglycerides,
and insulin in healthy, non-diabetic, and diabetic type 2 patients.

Methods:
Levels of glucose, triglycerides, and insulin in serum samples from 25 patients with
confirmed Diabetic type 2 disease and 30 normal controls were determined at 30, and 60 after the
ingestion of the drinks.

Results:
Levels of glucose, triglycerides, and insulin were notably higher in patients with diabetic
Mellitus compared with the normal group. Both triglycerides and insulin (60 min) were elevated
significantly above baseline after the intake of the artificial sweeteners in diabetic patients;
however, values for all other conditions across time were very stable.

Conclusion:
There is no reason to suppose that a higher consumption would result in an elevation
in these measures. Any noted insulin resistance linked to a high intake of artificial sweeteners
is likely a function of the excess calories and processed ingredients often included within artificially
sweetened food and beverage products.
Coexistence of Large Meningioma and Arteriovenous Malformation: A Case
Report and Literature Review
Authors: Wang Xue , Liu Yang , Tang Rong-Wu , Tao Zhu Ye 
Published: March 2023

Introduction:
The simultaneous presence of a giant intracranial meningioma and an arteriovenous malformation(AVM)in the same cerebral hemisphere is extremely rare. The treatment should be individualized depending on the case.

Case Presentation:
A 49-year-old man presented with hemiparesis. Preoperative neuroimaging revealed a giant lesion and an AVM on the left hemisphere of the brain. Craniotomy and tumour resection were performed. The AVM was not treated and needed to be followed up. The histological diagnosis was meningioma (World Health Organization grade I). The patient was in good neurological condition postoperatively.

Conclusion:
This case adds to the growing literature suggesting that the association between the two lesions is complex. Besides, treatment depends on the risk of neurologic function damage and hemorrhagic stroke of meningiomas and AVMs.
In silico Analysis of Natural Inhibitors against HPV E6 Protein
Authors: Vani Vemula , Venkateshappa Snehalatha , Nishitha Rachel , Shashidhar Hima , Hegde Arpitha B. , Alagumuthu Manikandan 
Published: March 2023

Background:
Drug re-purposing is one of the cost-effective methods to establish novel therapeutics against many diseases. Established natural products are collected from databases and used to potentially screen them against HPV E6 protein, a critical viral protein.

Objective:
This study aims to design potential small molecule inhibitors against HPV E6 protein
using structure-based approaches. Ten natural anti-cancerous compounds (Apigenin, Baicalein,
Baicalin, Ponicidin, Oridonin, Lovastatin, Triterpenoid, Narirutin, Rosmarinic Acid, and Xanthone)
were selected by review of the literature.

Methods:
These compounds were screened using Lipinski Rule of Five. Out of ten compounds,
seven were found to satisfy Rule of five. Docking of these seven compounds was carried out using
AutoDock software and corresponding Molecular Dynamics Simulations were performed by
GROMACS.

Results:
Among the seven compounds docked with the E6 target protein, six compounds showed
lesser binding energy than the reference compound, Luteolin. The three-dimensional structures
of E6 protein and the corresponding ligand complexes were visualised and analysed using PyMOL
whereas the two-dimensional images of protein-ligand interactions were obtained by LigPlot+
software to study the specific interactions. ADME analysis using SwissADME software revealed
that all the compounds except Rosmarinic acid have good gastrointestinal absorption
and solubility characteristics while Xanthone and Lovastatin showed blood brain barrier
penetration properties. Considering the binding energy and ADME analysis, Apigenin and
Ponicidin are found to be most suitable for de novo designing of potential inhibitors against the
HPV16 E6 protein.

Conclusion:
Further, synthesis and characterization of these potential HPV16 E6 inhibitors will
be carried out and their functional evaluation using cell culture-based assays will be undertaken.
Role of Supplements in the Management of COVID-19 - A Comprehensive
Review
Authors: Balasubramanian Rajkapoor , Maideen Naina Mohamed Pakkir , Muthusamy Sudha , Ramanathan Sambathkumar , Jahir Hussain Mohamed Harsath 
Published: March 2023

Abstract:
Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome
coronavirus-2 (SARS CoV-2) and patients with COVID-19 may be treated primarily with SARS CoV-
2-targeting drugs and the therapeutic agents assisting in the management of COVID-19 complications.
This review focuses on the supplements like vitamins, minerals, herbal constituents, and others that
help prevent or manage negative outcomes among COVID-19 patients. The literature was searched in
databases such as Medline/PubMed Central/PubMed, Google Scholar, Science Direct, EBSCO, Scopus,
EMBASE, the Directory of Open Access Journals (DOAJ), and reference lists to identify relevant
articles. The vitamins, including vitamin C, and vitamin D, minerals such as zinc, selenium, and copper,
herbal constituents like thymoquinone, curcumin, naringenin, quercetin, and glycyrrhizin, and
other supplements, including N-acetylcysteine and melatonin. Melatonin have been identified as having
the potential to manage patients with COVID-19 along with standard care. Some of the ongoing
clinical trials are investigating the effectiveness of different supplements among COVID-19 patients.
Developing an Inpatient Electronic Medical Record Phenotype for Hospital-Acquired Pressure Injuries: Case Study Using Natural Language Processing Models
Authors: Nurmambetova Elvira , Pan Jie , Zhang Zilong , Wu Guosong , Lee Seungwon , Southern Danielle A , Martin Elliot A , Ho Chester , Xu Yuan , Eastwood Cathy A 
Published: March 2023

Background
Surveillance of hospital-acquired pressure injuries (HAPI) is often suboptimal when relying on administrative health data, as International Classification of Diseases (ICD) codes are known to have long delays and are undercoded. We leveraged natural language processing (NLP) applications on free-text notes, particularly the inpatient nursing notes, from electronic medical records (EMRs), to more accurately and timely identify HAPIs.

Objective
This study aimed to show that EMR-based phenotyping algorithms are more fitted to detect HAPIs than ICD-10-CA algorithms alone, while the clinical logs are recorded with higher accuracy via NLP using nursing notes.

Methods
Patients with HAPIs were identified from head-to-toe skin assessments in a local tertiary acute care hospital during a clinical trial that took place from 2015 to 2018 in Calgary, Alberta, Canada. Clinical notes documented during the trial were extracted from the EMR database after the linkage with the discharge abstract database. Different combinations of several types of clinical notes were processed by sequential forward selection during the model development. Text classification algorithms for HAPI detection were developed using random forest (RF), extreme gradient boosting (XGBoost), and deep learning models. The classification threshold was tuned to enable the model to achieve similar specificity to an ICD-based phenotyping study. Each model’s performance was assessed, and comparisons were made between the metrics, including sensitivity, positive predictive value, negative predictive value, and F1-score.

Results
Data from 280 eligible patients were used in this study, among whom 97 patients had HAPIs during the trial. RF was the optimal performing model with a sensitivity of 0.464 (95% CI 0.365-0.563), specificity of 0.984 (95% CI 0.965-1.000), and F1-score of 0.612 (95% CI of 0.473-0.751). The machine learning (ML) model reached higher sensitivity without sacrificing much specificity compared to the previously reported performance of ICD-based algorithms.

Conclusions
The EMR-based NLP phenotyping algorithms demonstrated improved performance in HAPI case detection over ICD-10-CA codes alone. Daily generated nursing notes in EMRs are a valuable data resource for ML models to accurately detect adverse events. The study contributes to enhancing automated health care quality and safety surveillance.
Utilization and Effectiveness of a Message-Based Tobacco Cessation Program (mCessation) in the Chinese General Population: Longitudinal, Real-world Study
Authors: Su Zheng , Wei Xiaowen , Cheng Anqi , Zhou Xinmei , Li Jinxuan , Qin Rui , Liu Yi , Xia Xin , Song Qingqing , Liu Zhao , Zhao Liang , Xiao Dan , Wang Chen 
Published: March 2023

Background
Randomized controlled trials on text message interventions for smoking cessation have shown they are effective and recommended for tobacco control. However, the effectiveness in real-world settings is largely unknown, especially in low- and middle-income countries.

Objective
This study aimed to provide real-world evidence about the utilization and effectiveness of a message-based tobacco cessation program (mCessation) in China.

Methods
From May 2021 to September 2022, 16,746 people from the general population participated in the mCessation program provided by the World Health Organization. All participants received text messages on smoking cessation via instant messaging for 6 months, and they were also required to report smoking status. We randomly selected 2500 participants and interviewed them by telephone to determine the 7-day point prevalence abstinence rate at 6 months. Descriptive statistics were used to analyze population characteristics and abstinence rate. Logistic regression analysis was performed to explore risk factors for the abstinence rate.

Results
Among the 2500 participants, the mean age was 35 years, and most (2407/2500, 96.20%) were male. The prevalence of tobacco dependence and light degree of tobacco dependence were 85.70% (2142/2500) and 89.10% (2228/2500), respectively. For respondents (953/2500, 38.10%), the 7-day point prevalence abstinence rate at 6 months was 21.90% (209/953). Participants older than 40 years or with tobacco dependence had significantly higher abstinence rates than those who were younger than 30 years old (odds ratio [OR] 1.77, 95% CI 1.06-3.29) or without dependence (OR 1.64, 95% CI 1.08-2.51), respectively. However, married people or heavily dependent smokers tended to find it more difficult to successfully quit smoking compared with unmarried people (OR 0.57, 95% CI 0.34-0.93) or lightly dependent smokers (OR 0.16, 95% CI 0.02-0.98), respectively.

Conclusions
In a real-world setting, mCessation China was generally acceptable to men and lightly dependent smokers, and it could help 1 in 5 smokers aged 18 years to 67 years quit smoking. However, strategies to increase awareness of young and married adults may improve implementation and abstinence rates.
Digital Interventions for Treating Post-COVID or Long-COVID Symptoms: Scoping Review
Authors: Rinn Robin , Gao Lingling , Schoeneich Sarah , Dahmen Alina , Anand Kumar Vinayak , Becker Petra , Lippke Sonia 
Published: March 2023

Background
Patients with post-COVID/long-COVID symptoms need support, and health care professionals need to be able to provide evidence-based patient care. Digital interventions can meet these requirements, especially if personal contact is limited.

Objective
We reviewed evidence-based digital interventions that are currently available to help manage physical and mental health in patients with post-COVID/long-COVID symptoms.

Methods
A scoping review was carried out summarizing novel digital health interventions for treating post-COVID/long-COVID patients. Using the PICO (population, intervention, comparison, outcome) scheme, original studies were summarized, in which patients with post-COVID/long-COVID symptoms used digital interventions to help aid recovery.

Results
From all scanned articles, 8 original studies matched the inclusion criteria. Of the 8 studies, 3 were “pretest” studies, 3 described the implementation of a telerehabilitation program, 1 was a post-COVID/long-COVID program, and 1 described the results of qualitative interviews with patients who used an online peer-support group. Following the PICO scheme, we summarized previous studies. Studies varied in terms of participants (P), ranging from adults in different countries, such as former hospitalized patients with COVID-19, to individuals in disadvantaged communities in the United Kingdom, as well as health care workers. In addition, the studies included patients who had previously been infected with COVID-19 and who had ongoing symptoms. Some studies focused on individuals with specific symptoms, including those with either post–COVID-19 or long-term symptoms, while other studies included patients based on participation in online peer-support groups. The interventions (I) also varied. Most interventions used a combination of psychological and physical exercises, but they varied in duration, frequency, and social dimensions. The reviewed studies investigated the physical and mental health conditions of patients with post-COVID/long-COVID symptoms. Most studies had no control (C) group, and most studies reported outcomes (O) or improvements in physiological health perception, some physical conditions, fatigue, and some psychological aspects such as depression. However, some studies found no improvements in bowel or bladder problems, concentration, short-term memory, unpleasant dreams, physical ailments, perceived bodily pain, emotional ailments, and perceived mental health.

Conclusions
More systematic research with larger sample sizes is required to overcome sampling bias and include health care professionals’ perspectives, as well as help patients mobilize support from health care professionals and social network partners. The evidence so far suggests that patients should be provided with digital interventions to manage symptoms and reintegrate into everyday life, including work.
Diagnóstico al comportamiento tributario de los comerciantes de la ciudad de Ocaña
Authors: Ibañez Rueda Carmen Amanda 
Published: March 2023

Teniendo en cuenta las investigaciones propuestas por el Área de Investigación del El Centro de Investigación Desarrollo y Fomento Empresarial (CIDFE) adscrito a la Facultad de Ciencias Administrativas y Económicas (FCAE) de la Universidad Francisco de Paula Santander Ocaña (UFPSO), se realizó un diagnóstico al comportamiento tributario de los comerciantes de la ciudad de Ocaña, Norte de Santander, esto con el fin de identificar todos aquellos comerciantes que no pagan impuestos, o que desconocen de la obligatoriedad que tienen Estos en el cumplimiento del pago de los tributos.
Igualmente la investigación busca identificar las necesidades de capacitación que tienen los comerciantes de la ciudad de Ocaña en lo relacionado con las Leyes tributarias de nuestro país.
A su vez, para dar cumplimiento a los objetivos propuestos en la presente investigación, se conocerá sobre los aspectos metodológicos, usándose técnicas e instrumentos de investigación que permitan medir la cantidad de comerciantes de la ciudad de Ocaña que desconocen del pago de los impuestos o que evaden dicha obligación.
Responsabilidad social empresarial: ¿oportunidad o sofisma?
Authors: Pérez Suescún Leonardo Fabio 
Published: March 2023

En este artículo se presenta un análisis de la responsabilidad social empresarial como una oportunidad de materializar los postulados éticos que orientan el actuar organizacional, se fundamentó en los postulados teóricos de Argandoña. (2009), Bédard. (2003) Gómez. (2014), Holliday. (2010), Ruiz-Navarro. (2012) entre otros autores, se enmarca en una metodología documental y analítica. Se delibera sobre la importancia de la RSE como un valioso instrumento para la gestión integral de las organizaciones, adoptando principios que permitan abordar de manera integral el rol de la compañía dentro de la sociedad, dimensionando los aspectos económicos inherentes a la organización, pero también los sociales y ambientales propios del contexto donde desarrolla su actividad.
INVESTASI BODONG DENGAN SISTEM SKEMA PONZI: KAJIAN HUKUM PIDANA
Authors: Lorien Natalia , Tantimin Tantimin 
Published: March 2023

Perkembangan investasi saat ini telah mengalami kemajuan yang begitu cepat dan pesat. Investasi sendiri dalam hal ini telah dapat digunakan oleh para investor dengan menggunakan media aplikasi seperti aplikasi ‘alimana’ yang memanfaatkan perkembangan teknologi untuk menjalankan kegiatannya. Dan aplikasi ‘alimana’ di Indonesia merupakan aplikasi investasi bodong dengan skema ponzi, yang mana timbul permasalahan bahwa di Indonesia belum memiliki pengaturan secara khusus terkait dengan tindakan investasi bodong skema ponzi. Penelitian ini bertujuan untuk mengetahui bagaimanakah peran penegakan hukum terhadap para pelaku investasi bodong yang menggunakan skema ponzi dan Bagaimana upaya perlindungan hukum yang diberikan kepada korban dari investasi bodong skema ponzi pada aplikasi ‘alimana’. Penelitian ini menggunakan metode penelitian hukum normatif. Dan diketahui bahwa pelaku investasi bodong skema ponzi di Indonesia dapat dijerat dengan Pasal 378 KUHP tentang Penipuan dan karena tidak memiliki izin maka investasi bodong dapat dikenakan Pasal 103 Undang-Undang Nomor 8 Tahun 1995 tentang Pasar Modal dan terkait dengan korban investasi bodong skema ponzi pada aplikasi ‘alimana’ karena menggunakan media elektronik maka dapat dikenakan Pasal 28 ayat 1 Undang-Undang Nomor 11 Tahun 2008 tentang Informasi dan Transaksi Elektronik yang telah dirubah oleh Undang-Undang Nomor 19 Tahun 2016 tentang Perubahan atas Undang-Undang Nomor 11 Tahun 2008 tentang Informasi dan Transaksi Elektronik
MODEL PARAREM DESA ADAT DALAM MENCIPTAKAN TATANAN KEHIDUPAN BARU DI DESA UMEANYAR, KECAMATAN SERIRIT, KABUPATEN BULELENG
Authors: Sudiatmaka Ketut , Hadi I Gusti Ayu Apsari 
Published: March 2023

Penelitian ini bertujuan untuk menganalisis sistematika dalam bentuk konstruksi hukum pararem yang ideal bagi Desa Adat sebagai upaya menciptakan tatanan kehidupan baru (new normal) dan sekaligus pengintegrasian maupun penegakan hukum yang berlaku di Desa Adat Umeanyar, Kecamatan Seririt, Kabupaten Buleleng. Metode penelitian yang digunakan adalah yuridis empiris dengan mengumpulkan data penelitian berupa wawancara yang melibatkan Bendesa Adat Desa Umeanyar sebagai informan dan studi dokumen. Hasil penelitian menunjukkan Pararem No. 060/DA.Um/PRRM/VI/2020 memiliki konstruksi yang telah sesuai sebagaimana ketentuan menurut Peraturan Gubernur Bali No. 4 Tahun 2020 bahwa pararem disusun dalam bahasa Bali dan Bahasa Indonesia serta harus disosialisasikan kepada masyarakat desa adat. Selain itu dalam rangka pengintegrasian dan penegakan hukum pararem ini juga memuat sanksi dengan tingkat pembinaan, peringatan, hingga pamidanda seperti sanksi akilo beras, dasa kilo beras hingga selae kilo beras. Upaya pengintegrasian pararem hendaknya melibatkan segenap pihak mulai dari Bendesa Adat, Perbekel, Satgas Covid di wewidangan desa adat setempat.
EXPLORING SYNTACTIC AND CULTURAL PROBLEMS FACED BY TRANSLATORS IN TRANSLATING THE QURANIC ARABIC HOPE WORD L-AMALU لَمَألْا IN SURAHS AL-HIJR AND AL-KAHF INTO ENGLISH
Authors: Alhaj Ali Albashir Mohammed 
Published: March 2023

The translation of the uniqueness of the Holy Quran into English can be addressed and discussed from various linguistic and stylistic lexical, syntactic, and cultural views and standpoints. The Quranic Arabic words/terms are vivid and magnificent with several nuances of meaning; a case which makes it difficult to be rendered accurately. This study made an effort to analyze syntactic and cultural problems faced by translators in translating the Quranic Arabic hope words l-amalu لَمَألْا in Surahs Al-Hijr and Al-Kahf into English. The findings of the study showed that the translators of the Holy Quran into English faced cultural problems because Quranic Arabic culture-specific terms have no counterpart in the English culture. Also, part of the difficulties and quandaries in rendering such terms exists in the fact that these words need an awareness of the Arabic-Islamic culture with all its religious values and mores. The findings of the study also brought to light that the Quranic Arabic hope words l-amalu لَمَألْا are culture-specific par excellent. They denote a type of translation inequivalent because they cannot be adequately rendered by offering their denotative meanings.