bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic Review Protocol: Determining Factors Affecting Workforce Retention in Dentistry
Authors: Dorji Tenzin
Published: August 2024

BackgroundWorkforce retention is a critical and urgent problem in healthcare, significantly affecting service delivery, patient care, and organisational efficiency. In dentistry, the stability of the workforce is not just important; it is essential for maintaining access to and the quality of oral health services. Despite its urgency and importance, a comprehensive synthesis of the factors influencing retention in the dental sector is lacking. This systematic review seeks to fill this gap by evaluating the current literature and identifying critical determinants of dental workforce retention.Aim:The primary objective of this systematic review is to identify and analyse the factors that influence workforce retention globally, specifically in healthcare and dentistry. The review aims to inform effective retention strategies and policymakers in dental public health.Methods: This review will employ a systematic methodology to search, select, and synthesise relevant literature. Multiple databases including PubMed, Cochrane Library, Embase (Ovid), Medline (Ovid), and PsycINFO (Ovid) were searched using a combination of keywords related to "dentistry," "workforce retention," and "employment factors." The selection process involved rigorous screening of titles, abstracts, and full texts, adhering to predefined inclusion and exclusion criteria focusing primarily on observational studies, cross-sectional surveys, and qualitative research. Data extraction was standardized, and quality was assessed using established bias assessment tools. The synthesis was either thematic or meta-synthetic depending on the homogeneity of the data collected. The review is expected to identify a range of intrinsic and extrinsic factors, further classified as macro, meso, and micro factors, that significantly impact retention among dental health professionals. These may include but are not limited to job satisfaction, compensation, work environment, professional development opportunities, and organisational support. The findings will provide a basis for recommendations on how health policymakers and administrators in dental care institutions can improve workforce retention strategies and workforce stability, paramount for effective public health responses and sustainable healthcare delivery in dentistry.
Resolving of Inverse Problem Based on the One Component Linear Diffusion Model of Water Vapor Into Cellular Concrete Sample
Authors: Holubets Taras
Published: August 2024

In this paper the applying of inverse problem for calculation of diffusion coefficient distribution into porous cylindrical sample into one-dimensinal case is demonstrated. The main purpose of work is concentrated for adaptation of well know diffusion equation with boundary conditions to experimentally obtained humidity profiles into porous sample. Empirical equations for diffusion coefficients according to obained humidity distribution are also reviewed. The proper physical interpretation of water vapor diffusion coefficient for coordinate and time dependencies is proposed. For this purpose the averaged quantities are introduced
A chromosome-scale genome of the Korean cultivar Sesamum indicumvar. Goenbaek provides insight into its oil-seed quality and health-promoting gene repertoire
Authors: Zoclanclounon Yedomon Ange Bovys , Thamilarasan Senthil Kumar , Mo Youngjun , Ahn Byoung-Ohg , Kim Jeong-Gu , Lee Keunpyo
Published: August 2024

Sesamum indicum seeds are omnipresent in Korean dietary habits as food decorations, and the oil is used in traditional medicine due to its natural antioxidant content. Although genomic resources are available mainly from Chinese and Indian genotypes, the lack of Korean genomic resources hampers the design of novel genotypes with valuable agronomic importance as well as food and health-enhancing properties. This study aimed to generate a high-quality chromosome-level genome of the Korean cultivar Goenbaek, which is rich in oil, sesamin, and sesamolin. The combination of short- and long-reads and chromosome conformation capture data helped to assemble the genome into 13 chromosomes spanning 262.5 Mbp with an N50 value of 19.9 Mbp. A total of 23,539 protein-coding genes were predicted. Phylogenetic analysis placed Goenbaek on a distinct branch, suggesting geographical or adaptive patterns leading to genetic diversity. Goenbaek exhibited a set of 1,171 species-specific gene families enriched in lipid metabolism and biosynthesis, fatty acid metabolism, and phenylpropanoid biosynthesis, which confirmed its rich oil content. In addition, health-beneficial genes related to sphingolipid and selenocompound metabolism were also identified. The new reference-grade genome will serve as a reference for the Korean genomics-assisted sesame breeding program for the improvement of agronomic traits and for the investigation of oil and specialized metabolites.
Charlotte Houtermans, 1899–1993
Authors: Kremmel Stefanie
Published: August 2024

Die Wissenschaftlerin Charlotte Houtermans übersetzte Anfang der 1930er Jahre in Berlin und dann auch in ihrem amerikanischen Exil hoch spezialisierte Texte aus ihrem eigenen Fach, der Physik, sowohl aus dem Englischen ins Deutsche wie auch umgekehrt aus dem Deutschen ins Englische.
Towards a data-driven model of hadronization using normalizing flows
Authors: Bierlich Christian , Ilten Philip , Menzo Tony , Mrenna Stephen , Szewc Manuel , Wilkinson Michael K. , Youssef Ahmed , Zupan Jure
Published: August 2024

We introduce a model of hadronization based on invertible neural networks that faithfully reproduces a simplified version of the Lund string model for meson hadronization. Additionally, we introduce a new training method for normalizing flows, termed MAGIC, that improves the agreement between simulated and experimental distributions of high-level (macroscopic) observables by adjusting single-emission (microscopic) dynamics. Our results constitute an important step toward realizing a machine-learning based model of hadronization that utilizes experimental data during training. Finally, we demonstrate how a Bayesian extension to this normalizing-flow architecture can be used to provide analysis of statistical and modeling uncertainties on the generated observable distributions.
CURTAINs flows for flows: Constructing unobserved regions with maximum likelihood estimation
Authors: Sengupta Debajyoti , Klein Sam , Raine John Andrew , Golling Tobias
Published: August 2024

Model independent techniques for constructing background data templates using generative models have shown great promise for use in searches for new physics processes at the LHC. We introduce , a major improvement to the CURTAINs method by training the conditional normalizing flow between two side-band regions using maximum likelihood estimation instead of an optimal transport loss. The new training objective improves the robustness and fidelity of the transformed data and is much faster and easier to train. We compare the performance against the previous approach and the current state of the art using the LHC Olympics anomaly detection dataset, where we see a significant improvement in sensitivity over the original CURTAINs method. Furthermore, CURTAINsF4F requires substantially less computational resources to cover a large number of signal regions than other fully data driven approaches. When using an efficient configuration, an order of magnitude more models can be trained in the same time required for ten signal regions, without a significant drop in performance.
Non-chiral vertex operator algebra associated to Lorentzian lattices and Narain CFTs
Authors: Singh Ranveer Kumar , Sinha Madhav
Published: August 2024

Frenkel, Lepowsky, and Meurman constructed a vertex operator algebra (VOA) associated to any even, integral, Euclidean lattice. In the language of physics, these are examples of chiral conformal field theories (CFT). In this paper, we define non-chiral vertex operator algebra and some associated notions. We then give a construction of a non-chiral VOA associated to an even, integral, Lorentzian lattice and construct their irreducible modules. We obtain the moduli space of such modular invariant non-chiral CFTs based on even, self-dual Lorentzian lattices of signature (m,n)(m,n) assuming the validity of a technical result about automorphisms of the lattice. We finally show that Narain conformal field theories in physics are examples of non-chiral VOA. Our formalism helps us to identify the chiral algebra of Narain CFTs in terms of a particular sublattice and give us the decomposition of its partition function into sum of characters.
Periodic Determination of Physical and Physiological Responses to High Temperature Stress in cv. Narince Grapes
Authors: Altıncı N. Topcu , Cangi R.
Published: August 2024

Stress is a condition that affects or even inhibits growth, development and metabolism in plants. The type of stress, duration of application and severity also affect plants significantly. In this study, the weekly responses of Narince, a wine grape variety, to high temperature stress (HTS) in in vitro conditions were followed and stress was applied in two different periods, for 12 and 18 hours at 40°C. Some growth development (viability, fresh shoot weight, dry shoot weight, number of leaves, shoot length), physiological (ion flow and relative water content (RWC)) and biochemical (malondialdehyde (MDA)) analyses were done, with weekly follow-ups after the applications. In addition, the damage was graded visually. At the end of the application of both stresses, the percentage viability rate started to decrease. This rate decreased more slowly during HTS for 12 hours, while a faster decrease was observed in HTS for 18 hours. The number of healthy plants to be evaluated could not be reached after the fourth week. Growth and development parameters – fresh shoot weight (g), dry shoot weight (g) and shoot length (mm) – decreased after both stress applications, and these values were found to be statistically significant. After 12 hours of HTS application, the highest MDA value was determined at 0.274 nmol in the sixth week, while the lowest MDA value was determined in the first week, at 0.137 nmol. After 18 hours of HTS application, the highest MDA value was determined in the fourth week, at 0.263 nmol, while the lowest MDA value of 0.103 nmol was determined in the first week.
Long-term Effects of Irrigation with Treated Municipal Wastewater on Soil Chemical and Physical Responses in Commercial Vineyards in the Coastal Region of South Africa
Authors: Hoogendijk K. , Myburgh P.A. , Howell C.L. , Lategan E.L. , Hoffman J.E.
Published: August 2024

The prolonged drought in the Western Cape province of South Africa in recent years has been particularly detrimental to the wine industry. Water restrictions imposed by authorities and the limited supply of fresh water that can be stored, have emphasisedthe need for alternative water sources for vineyard irrigation. Treated municipal wastewater has been used successfully as an alternative source of irrigation water in other countries. A long-term trial was conducted in commercial vineyards in the Coastal region of South Africa to assess the impact of treated municipal wastewater irrigation on vineyards. Cabernet Sauvignon and Sauvignon blanc grapevines were irrigated using treated municipal wastewater from the Potsdam wastewater treatment works for 11 years. Grapevines were either rainfed (RF), irrigated with treated municipal wastewater via a single dripper line (SLD), or received twice the volume of wastewater via a double dripper line (DLD). Irrigation using treated municipal wastewater increased soil pH(KCl), the electrical conductivity of the saturated extract (ECe) and Cl-. Substantial amounts of Na+ and K+ accumulated in the topsoil due to irrigation with treated municipal wastewater. These soil K+ increases could have a negative effect on wine colour stability should the levels of soil K+ be such that they are absorbed excessively by grapevines. The near-saturation hydraulic conductivity (Kns) at the surface of the soil could be related to the ECe in the topsoil. The results represent specific in-field situations in three commercial vineyards under one set of climatic conditions.
Factors Affecting the Liquidity Risk of Commercial Banks in Nepal
Authors: Niroula Ballav , Gnawali Bindu
Published: August 2024

Level liquidity is an important factor that helps the growth and survival of commercial banks.  This research aims to show the factor affecting the liquidity risk of commercial banks in Nepal. The panel data were used to analyze and find the results from the period 2017 to 2021. Secondary data are collected from the annual report of commercial banks. Banks’ internal factors bank size, capital adequacy ratios, non-performing loans, return on assets, return on equity, and external factor gross domestic product was used as independent variables. The dependent variable of the research is the liquidity ratio. A descriptive research design has been used to explain the data. A convenient sampling technique was used to select the 16 commercial banks as a sample from the population of 26 banks. Various statistical methods are used to describe the data and to find the result from the 80 observations. The result shows that there is a significant and negative relationship between bank size and non – performing loans with the liquidity of commercial banks in Nepal, but GDP, ROA, and ROE have significant positive effects on liquidity. To maintain the liquidity level commercial banks, need to minimize the non – performing loans. It is crucial to take into account the size of the bank, the nature of the crisis, the regulatory environment, the interconnection of the financial sector, market perception, and contagion risk when large banks have a negative impact on liquidity. Knowing these elements will make it easier to find suitable answers to the liquidity issue and lessen the effects it has on the larger financial system.
Strategi Bauran Pemasaran Ayam Zata Tahun 2023-2025
Authors: Ramadhan Muhammad Taqiyyuddin , Widjaja Andrianto
Published: August 2024

Penelitian ini merupakan penelitian terapan yang ditujukan untuk mengetahui masalah pemasaran yang dihadapi Ayam Zata dan menyusun strategi pemasaran baru yang tepat dan efektif sesuai dengan target pasar Ayam Zata. Penelitian ini menggunakan pendekatan kualitatif dan kuantitatif. Penelitian ini sendiri dilakukan pada gerai Ayam Zata cabang Cipinang Muara dan observasi yang dilakukan disekitar gerai sejauh 200 meter. Berdasarkan hasil penelitian, pelanggan telah memberikan persepsi bahwa Ayam Zata merupakan gerai aneka olahan ayam. Sambal bawang yang dimiliki Ayam Zata cukup disukai konsumen. Strategi pemasaran yang dilakukan Ayam Zata belum optimal karena masih sederhana. Promosi yang dilakukan sebatas melalui banner.
Examining the Locus of Control, Auditor Experience, Self-Efficacy and Task Complexity for Audit Judgment
Authors: Sabilillah Rhalia , Hardi Hardi , Safitri Devi
Published: August 2024

This research goals to specify The Influence of Locus of Control, Auditor Experience, Self-efficacy and Task Complexity on Audit judgment (Empirical study at KAP in Pekanbaru and Padang). This research method use quantitative research method. The occupant in this research are auditors in the Pekanbaru and Padang areas. The sample in this study was 39. Data analysis was brought out use classic contention tests and hypothesis examine using the lots of regression method. The difference between this study and the reference journal (Yowanda et al. 2019) is the location of the study, the variables used and the year of the study. Based on the research yields, it shows that The Auditor's Experience, Self-efficacy and Task Complexity have an influence on Audit judgment in the Pekanbaru and Padang areas, while the Locus of Control variable hasn’t clout on Audit judgment in the Pekanbaru and Padang areas.
Gender and age-related peculiarities in manifestation of different aggression types in older adolescents
Authors:   Moscow Pedagogical State University, Egorova Anna , Rean Artur ,   Federal Scientific Center of Psychological and Multidisciplinary Research, Tikhomandritskaya Olga ,   Lomonosov Moscow State University
Published: August 2024

This article is dedicated to the study of gender and age-related peculiarities in manifesting different aggression types in older adolescents. A theoretical literature review on the problem is presented with a particular emphasis on the dynamics in various aggressive manifestations in adolescents, age and gender related peculiarities in these manifestations, and the analysis of factors that may determine the differences in manifestation of aggression in boys and girls of different age groups. The results of an empirical study conducted on a large-scale sample of adolescents (N = 10 980) aged 15 to 18 years are presented. The data analysis shows that physical aggression is more pronounced in male respondents, while hostility and displays of anger are more pronounced among the female respondents. One-factor analysis of variance demonstrates a statistically significant influence of gender on the expression of all the aggression types. The largest effect size is observed in relation to anger, and the smallest — in expressions of hostility. We have also established the age-related differences in aggressive manifestations within the different aggression types in older adolescents. It was shown that physical aggression decreases significantly between the ages of 15 and 18, while anger and hostility manifestations remain stable after the age of 15. The effect of age on the expression of aggression was also statistically significant within all the aggression types. The largest effect size was observed for physical aggression, the smallest — for anger. The obtained results confirm the need to consider the age and gender characteristics when creating anger management and aggression prevention programs and to expand the research base of gender and age characteristics in adolescent aggression. Also, these results can be used for developing educational and preventive technologies for working with adolescent aggression.
Age-related changes in autism spectrum disorder symptoms among children 3-9 years old
Authors:   St. Petersburg State University, Pakhomova Yekaterina , Nasledov Andrey ,   St. Petersburg State University, Tkacheva Lubov O. ,   St. Petersburg State University
Published: August 2024

The study focuses on examining of age-related changes in ASD symptoms among children 3-10 years old. Sample consisted of 70 children, of which 21 were children without ASD, but with autistic traits. 881 children from the previous studies were included. The following symptom groups were investigated: 1) “Communication impairments”, 2) “Emotional disturbances”; 3) “Sensory disintegration”; “Disinhibition”; 5) Overall symptoms. Assumptions of this study: 1) there are age-related differences in ASD symptoms among children aged 3-10 years. Results found that overall symptoms statistically significant decreased for ASD children, as well as communication impairments, emotional disturbances, sensory disintegration. Additionally, for children without ASD decreasing is not registered.
Structural and Communicative Models with Target Semantics in a Complex Sentence in the Practice of Teaching Russian as a Foreign Language
Authors:   Lomonosov Moscow State University, Odintsova Irina V.
Published: August 2024

The article deals with complex sentences of the goal from the point of view of their teaching in a foreign audience. The use of complex target sentences is one of the most difficult topics in the practice of teaching Russian as a foreign language. In linguistic literature, the expression of target relations by a complex sentence does not find an unambiguous interpretation: there is a wide and narrow understanding of these sentences. Appeal in the practice of teaching Russian as a foreign language to the concept of a structural-communicative model allows us to limit the use of target sentences to cases of expressing self- and non-self-target relations. Such a division of syntactic relations expressed in a sentence is extremely relevant in Russian as a foreign language, since it reflects, firstly, the dynamics of the presentation of grammatical material depending on the level of foreign students’ language proficiency, and secondly, determines the volume of this material. Self-goal relations, expressed by means of a complex sentence, constitute the core as the most stable part of the functional-semantic field. These relations convey the meaning of the goal — the expression of the desired result as a purposeful action of the subject — in the most general form. In non-target sentences, goal relations are transformed into “purpose” relations, and the subject, represented explicitly or implicitly, is conceived as an indirectly subjective deagent carrier of the attribute. The main means of expressing proper and non-propertarget relations is the union to or its modifications: in order to, in order to, then in order to, in order to, in order to.
Long-term performance of wastewater gardens: follow-up on the status of the wastewater garden in Temacine – Algeria
Authors: Rokbane Abdelmadjid , Zorai Ameur , Ouakouak Abdelkader
Published: August 2024

This work investigated the long-term performance of a small wastewater garden (WWG) system for treating municipal wastewater, which has been operating continuously since 2007. The studied system consisted of a horizontal subsurface flow (HFCW) and treated a flow rate of 15 m3/day. Results from 15 years of operation showed that the system has an average removal efficiency of 90.76, 85.12, 89.43, 66.87, 94.74, and 94.74% for total suspended solids (TSS), chemical oxygen demand (COD), biochemical oxygen demand (BOD5), nitrites (NO2–), nitrates (NO3–), and orthophosphates (PO43−), respectively. The high efficiency of the WWG plant was achieved during 2018–2022 compared to the two first years of operation (apart from the TSS). It was noted that the removal of BOD5, NO2–, NO3–, and PO43− has been improved in the last years of operation. The elimination COD remained relatively consistent between the initial and present period of operation. The finding confirms the high efficiency in the long-term operation of municipal wastewater treatment. Thus, it can serve as a suitable solution for small communities, especially in arid climate areas.
IMPORTANCIA CULTURAL DE LAS PLANTAS MEDICINALES EN EL DISTRITO DE QUINUA (AYACUCHO, PERÚ)
Authors: Hurtado-Huarcaya Jose
Published: August 2024

Desde tiempos remotos las plantas medicinales han constituido un recurso muy importante en la vida diaria del poblador peruano, por ello la importancia de estudios relacionados a este recurso. La presente investigación tuvo como objetivo realizar un estudio etnobotánico y determinar la importancia cultural de las plantas medicinales del distrito de Quinua (Huamanga, Ayacucho). Se recolectaron especímenes de la flora medicinal silvestre y se formularon entrevistas abiertas y semiestructuradas a los pobladores del lugar. Se reportan 115 especies medicinales agrupadas en 90 géneros y 44 familias con mayor representación de especies en Asteraceae (33 spp.), Fabaceae (10 spp.), Lamiaceae (siete spp.) y Solanaceae (cinco spp.). Se registran 17 subcategorías de dolencias y/o enfermedades, siendo los trastornos del sistema digestivo, sistema genitourinario, inflamaciones, sistema músculo esquelético, sistema respiratorio y síndromes culturales los que mayor número de especies presentaron con 101, 76, 76, 64, 59 y 50 especies, respectivamente. Las plantas medicinales de mayor importancia cultural son Urtica urens, Equisetum bogotense, Plantago major, Oenothera rosea, Tara spinosa, Ambrosia arborescens, Clinopodium brevicalyx, Lupinus ballianus, Schinus molle y Clinopodium breviflorum. Finalmente, los pobladores del distrito de Quinua poseen un gran conocimiento sobre las plantas medicinales y aún las siguen utilizando dentro de la medicina tradicional.
New Horizons in Antiretroviral Drug Delivery Systems for HIV Management
Authors: Almeida dos Santos Kayque , Maria Coelho de Carvalho Moreira Lívia , Lamartine Soares-Sobrinho José , Felts de La Roca Soares Mônica
Published: August 2024

Introduction: Human Immunodeficiency Virus (HIV) infection is still a major global problem, whose drug treatment consists of prophylactic prevention and antiretroviral combination therapy for better pharmacological efficacy and control of circulating virus. However, there are still pharmacological problems that need to be overcome, such as low aqueous solubility of drugs, toxicity, and low patient adherence. Drug delivery technologies can be used to overcome these barriers.
Objective: This review summarized the latest drug delivery systems for HIV treatment. Initially, an overview of the current therapy was presented along with the problems it presents. Then, the latest drug delivery systems used to overcome the challenges imposed in conventional HIV therapy were discussed.
Conclusion: Articles published in the last 10 years were reviewed to obtain information on the innovations brought to HIV treatment. Delivery systems can improve the physicochemical properties of antiretroviral drugs, causing greater aqueous solubility, stability, and cellular and membrane permeability, which was reflected in the greater bioavailability of these drugs. However, more stability studies and techniques development are still needed to allow industrial scaling for large-scale production of drugs that use these technologies.
Jingzhi Niuhuangjiedu Tablet Ameliorates Oral Mucositis via the AKT/NFκB/NLRP3 Signaling Pathway: A Network Pharmacology and Experimental Validation
Authors: Fan Chunlan , Wang Hongping , Yin Qiong , Li Pin , Ma Quantao , Lin Zhaozhou , Zhao Chen , Peng Ping , Wang Zijian , Lv Yingnan , Wang Zhibin
Published: August 2024

Background:

Oral Mucositis (OM) is a common and highly symptomatic complication
of cancer therapy that affects patient function and quality of life. Jingzhi Niuhuangjiedu Tablet
(JNT) is derived from the famous Chinese herbal formulas Huanglian Jiedu and Fangfeng
Tongsheng decoctions, which have been widely used to treat heat toxin syndrome diseases, such as
acute pharyngitis, periodontitis, oral ulcers, and oral mucositis (OM), but the underlying mechanism
remains unclear.

Objectives:

This study validated the efficacy and explored the potential mechanisms of JNT in the
treatment of OM by integrating network pharmacological analyses and experimental verification.

Methods:

Network pharmacology and molecular docking techniques were used to predict the active
components, key targets, and potential mechanisms of action of JNT against OM.
The rat OM model was established by administering 5-Fluorouracil (5-FU) and acetic acid to the
rat oral mucosa. Lipopolysaccharide (LPS)-treated human gingival fibroblasts (HGFs) were used
as an inflammatory cell model. The GFP-NFκB HEK293T cell line was transfected to evaluate the
anti-NFκB activity of JNT.

Results:

A total of 236 Chinese herbal components and 201 corresponding targets were predicted
for OM treatment using JNT. Bicuculine, luteolin, wogonin, and naringenin were identified as the
important active compounds, while AKT1, ALB, IL6, MAPK3, and VEGFA were considered to be
the major targets. Molecular docking revealed that these active compounds exhibited strong binding
interactions with their targets. In vivo and in vitro experiments demonstrated that the anti-OM
effect of JNT might be closely related to AKT1, NFκB, caspase-1, and NLRP3, as well as biological
processes, such as inflammatory response and oxidative stress.

Conclusion:

Network pharmacological and experimental evidence indicates that JNT has a potential
therapeutic effect on OM by regulating the Akt/NFκB/NLRP3 pathway.
Caffeic Acid Reduces Ferroptosis to Dampen Inflammation of Keratinocytes in Psoriasis by Inhibiting EGR1-induced Transcription Activation of CHAC1
Authors: Li Yadi , Zhou Xiaoqian , Yang Zhusheng , Zhang Lichao , Yang Xiumin , Wei Aihua
Published: August 2024

Background:

Ferroptosis of keratinocytes is closely associated with
amplification of skin inflammation in psoriasis. This study focuses on unlocking the role
of caffeic acid (CA), a polyphenol compound, in keratinocyte ferroptosis and
understanding the underlying mechanistic basis.

Methods:

The interaction between early growth response protein 1 (EGR1) and chac
glutathione specific γ‑glutamylcyclotransferase 1 (CHAC1) was predicted by
bioinformatics and validated via chromatin immunoprecipitation and dual-luciferase
reported assays. Their expressions in primary human epidermal keratinocytes were
altered by transfection of EGR1/CHAC1 overexpression or knockdown plasmids, and
then keratinocytes were followed by CA treatment and Erastin (ferroptosis inducer).
Keratinocyte viability was determined by CCK-8 assay, and the ferroptotic effect was
evaluated using colorimetric assay and flow cytometry. Proinflammatory cytokine
secretion by keratinocytes was detected via ELISA. Expressions of EGR1 and CHAC1
in keratinocytes were analyzed by qRT-PCR or Western blot.

Results:

Increased expressions of EGR1 and CHAC1 were detected in keratinocytes
with Erastin treatment. CA (100 μM) antagonized Erastin (10 μM)-induced decrease in
viability, increases in EGR1 and CHAC1 expressions, upregulation of MDA, ROS, and
Fe2+, downregulation of GSH and SOD, and secretion of proinflammatory cytokines
from keratinocytes. EGR1 overexpression potentiated Erastin-induced effects.
Moreover, EGR1 overexpression and CA mutually counteracted their effects on
Erastin-induced keratinocytes. EGR1 transcriptionally activated and positively
regulated CHAC1. The above Erastin-induced effects were neutralized by EGR1
knockdown but potentiated by CHAC1 overexpression. Moreover, EGR1 knockdown
and CHAC1 overexpression reversed each other's effects.

Conclusion:

CA reduces ferroptosis by inhibiting EGR1-induced activation of CHAC1
to dampen inflammation of keratinocytes in psoriasis. This study providing new
compounds and candidate targets for the clinical treatment of psoriasis.
Synthesis of Isatin-derived Heterocycles with Promising Anticancer Activities
Authors: Banerjee Bubun , Sharma Aditi , Singh Arvind , Kaur Manmeet , Priya Anu
Published: August 2024

Isatin or 1H-indole-2,3-dione skeleton has been playing a significant role in drug design
and development. Isatin itself and many of its derivatives are widely distributed in naturally
occurring bioactive compounds. Various synthetic isatin derivatives were found to possess a
broad range of significant pharmacological efficacies especially anti-cancer activity against a
wide variety of cancer cell lines. Interestingly, on a few occasions, some isatin-derived scaffolds
were reported as more potent than the tested reputed drug molecules. As a result, isatin-derived
compounds have been gaining significant attention in cancer-based drug developments. In this review,
we have summarized literature reported during the last two decades related to the synthesis
of structurally diverse isatin-derived scaffolds with promising anti-cancer activities.
Frequency of Human Leukocyte Antigen-B*57:01 Allele Carriers in People Living with HIV/AIDS in Türkiye
Authors: Yılmaz Erkan , Kurt Ahmet Furkan , Dogruel Mehtap , Sevgi Dilek Yıldız , Karaosmanoglu Hayat Kumbasar , Zerdali Esra , Meric Koc Meliha , Mete Bilgul , Tabak Fehmi
Published: August 2024

Introduction:

Abacavir is among the first-line initial antiretroviral regimens for most
patients living with HIV/AIDS (PLWHA). Although well tolerated, it is associated with hypersensitivity
reaction (HSR), which is treatment-limiting and potentially life-threatening. HSR was
shown to be associated with the class I MHC allele, HLA-B*57:01. In this study, we aimed to
evaluate the prevalence of HLA-B*57:01 in PLWHA in Istanbul, Türkiye.

Material and Methods:

Five HIV treatment centers in Istanbul included all sequential treatment--
naïve, ≥ 18 years adult PLWHA, between December 2017- December 2021. Demographic, clinical,
and laboratory data were collected at baseline and during treatment. HLA-B* 57:01 genotyping
was determined with PCR-SSP.

Results:

Eight hundred sixty-seven PLWHA were included (male:91%, mean age 39.6±11.1
years). 1.6% of patients were found to be HLA-B*57:01 positive. Among HLA-B*57:01 positive
patients, 4 were initially given abacavir-containing treatment; they were switched to non-abacavir
treatment upon the allele found to be positive.

Conclusion:

Although previous studies reported the HLA-B*57:01 prevalence of PLWHA in
Türkiye as 3-3.6%, we have found the prevalence to be 1.6%. The current study includes higher
numbers of patients than the previous studies. Furthermore, patients from all over the country apply
to the centers in Istanbul; compared to the other studies, which involve patients limited to the
relevant regions, it can be assumed that the number in our cohort is more representative of the
country. In conclusion, the prevalence of the HLA-B*57:01 allele in PLWHA in this study is relatively
low. With evident benefit in preventing abacavir HSR, HLA-B*57:01 should be screened in
planning antiretroviral therapy.
Molecular Docking and Modelling Studies for Identifying Novel Oxadiazole Derivatives to Inhibit COX-2 Enzyme as an Anti-Inflammatory Treatment
Authors: Chaudhary Tarun , Upadhyay Prabhat Kumar , Kataria Ritu
Published: August 2024

The objective of the study was to develop new Oxadiazole compounds using docking
simulation studies for inhibitory action against the Cycloxoygenase-2(COX-2) enzyme. The study
aimed at the development and identification of novel and potent derivatives of 1,3,4-oxadiazole for
targeting anti-inflammatory disease by screening their inhibitory action against COX-2 enzyme with
schrodinger molecular docking software and molecular simulation by GROMACS 2022. A library of
375 novel compounds of 1,3,4-oxadiazoles derivatives was designed and proposed for docking
against cyclooxygenase-2 enzyme (COX-2)PDB ID: 6BL4, which was downloaded from protein
data bank site https://www.rcsb.org/. MD simulations for three models were performed, namely,
compound A-Cox-2, E-Cox-2, and G-Cox-2, for 100 ns. Out of 375 proposed compounds, the top 16
compounds with good docking scores and binding energy were selected for further ADME profile
studies in which all compounds showed good results as compared to Standard drugs. RMSD values
of 0.2 nm showed that all ligand-Cox-2 complexes were stable during simulation. Compound G was
the most efficient in decent interactions with the residues ARG120 and TYR355 of cyclooxygenase-
2, which were stable for 29.32, 21.52, and 12.00% duration of simulation along with comparatively
better h-bond contacts. All potential inhibitors met Lipinski's rule of five, indicating oral availability.
The potential compounds may be further evaluated for pharmacological activities using different in
vitro and in vivo evaluations.
Integration of Diabetes Mellitus and Hypertension on Major Cardiovascular Events: An Experience From a 15-year Follow-up Cohort Study in EMR
Authors: Sadeghi Masoumeh , Teimouri-Jervekani Zahra , Roohafza Hamidreza , Talaei Mohammad , Paknahad Mohammad Hossein , Dianatkhah Minoo , Boshtam Mansoureh , Sarrafzadegan Nizal
Published: August 2024

Introduction:

Patients with hypertension and diabetes are more susceptible to cardiovascular
diseases (CVD) and mortality. This study aimed to evaluate the individual and combined
effects of hypertension and diabetes on cardiovascular events and mortality in a Middle
Eastern population-based cohort.

Methods:

Fifteen-year follow-up data were collected for 6323 adults aged 35 years and older
who were free from CVD at baseline. The subjects were categorized into different groups according
to hypertension and diabetes at baseline. Cox proportional hazards regression was implemented
to estimate hazard ratios (HRs) of hypertension and diabetes for cardiovascular events
(CVE), CVD mortality, and all-cause mortality. Population-attributable hazard fraction (PAHF)
was used to assess the proportion of hazards of CVE and mortality attributable to hypertension or
diabetes.

Results:

The incidence rates (95% CI) of CVE, CVE mortality, and all-cause mortality in the total
population were 13.77(12.84-14.77), 3.01(2.59-3.49), and 9.92(9.15-10.77) per 1000 persons
per year respectively. The HR of hypertension for CVE in the diabetic population was 1.98
(1.47-2.66) with a PAHF of 27.65(15.49-39.3). When the HRs and PAHF of diabetes were evaluated
in hypertensive patients, they were statistically significant for CVE, CVE mortality, and
all-cause mortality.

Conclusion:

Our study indicated that the joint effect of diabetes and hypertension is the dramatic
increased risk of CVE. A considerable fraction of the excess risk of CVE in patients with diabetes
was attributable to hypertension, on the other hand, diabetes was associated with a substantial
hazard fraction of CVE and mortality in hypertensive patients.
Synthesis and Evaluation of Antibacterial and Antifungal Activities In vitro and In silico of Novel Morpholinoalkoxychalcones
Authors: Phan Hoang Minh , Mai Tan Thanh , Don Thinh Nguyen Quang , Do Dat Thanh , Thai Khac Minh , Tran Thanh Dao , Truong Phuong , Huynh Phuong Nguyen Hoai
Published: August 2024

Introduction:

Chalcone compounds exhibit diverse bioactivities, attracting significant
interest. Morpholine is a heterocycle commonly used in medicinal chemistry. It could enhance the
potency, pharmacokinetics, and bioactivities of its compounds.

Methods:

Adding morpholine into the chalcone scaffold could help create new compounds with
favorable bioactivities. In this study, a new parallel synthesis procedure has been developed. Using
this procedure, 18 novel morpholinoalkoxychalcones have been successfully synthesized. They had
chains with morpholine appended on ring A or ring B. All the synthesized compounds were
evaluated for the antibacterial and antifungal activities by agar diffusion method on 5 bacteria and 2
fungi strains.

Results:

The compounds with good inhibition were determined with respect to the MIC values by
the agar dilution method. Among the tested compounds, B.21 was found to be the best against E.
faecalis, with an MIC value of 0.6 mM. B.43 with an MIC value of 2.04 mM has displayed its potential
in inhibiting A. niger and C. albicans the best among other compounds.

Conclusion:

The in silico study has revealed two targets to align with the in vitro results. Longer
alkyl chains have enhanced the activity, along with the presence of OH, NH2, and halogen groups
on both rings A and B.
Exploring Thiophene Derivatives: Synthesis Strategies and Biological Significance
Authors: Mishra Isha , Sharma Vikram , Kumar Nitin , Krishna Gaurav , Sethi Vandana Arora , Mittal Ravi , Dhakad Prashant K. , Mishra Raghav
Published: August 2024

Objectives:

Thiophene is one of the most important heterocyclic scaffolds with notable
pharmacological properties. Thiophene and its derivatives are of particular interest among sulphurcontaining
heterocycles because of their similarities to numerous natural and synthetic compounds
with identified potential. The purpose of this study is to extensively analyse the synthetic pathways
adopted for synthesising thiophene derivatives and investigate their various biological functions.

Methods:

A comprehensive review of the existing literature was conducted to collect data pertaining
to the methods that are employed for the synthesis of thiophene derivatives. A comprehensive
search was carried out through relevant databases, including work published in 2024. A variety of
synthesis procedures were identified and arranged, encompassing both traditional approaches like
the Gewald reaction and contemporary ones like microwave-assisted synthesis and green synthesis.
In addition, a comprehensive compilation of in vitro and in vivo studies was conducted to investigate
the biological effects of 50 distinct thiophene derivatives. The primary focus of the studies was
on various activities such as anti-cancer, anti-inflammatory, antiprotozoal, antibacterial, antioxidant,
and antiviral functions.

Results:

Diverse methodologies have been employed in the synthesis of thiophene derivatives,
encompassing both conventional and modern methods. Furthermore, the biological potential of
thiophene derivatives was investigated, demonstrating a broad range of actions. Key structural elements
necessary for biological activity were clarified by investigations of the structure-activity
relationship.

Conclusion:

The biological potential and flexible synthesis pathways of thiophene derivatives
make them attractive candidates for use in medicinal and pharmaceutical chemistry. Understanding
the different synthesis methods and biological actions of thiophene derivatives may assist rational
design and create novel treatments for a variety of conditions. The potential for these compounds to
be further explored and optimised is considerable for the next drug development initiatives.
Cyclanoline Reverses Cisplatin Resistance in Bladder Cancer Cells by Inhibiting the JAK2/STAT3 Pathway
Authors: Li Linjin , Li Chengpeng , Miao Feilong , Chen Wu , Kong Xianghui , Ye Ruxian , Wang Feng
Published: August 2024

Background:

Cisplatin is a key therapeutic agent for bladder cancer, yet the emergence of cisplatin
resistance presents a significant clinical challenge.

Objective:

This study aims to investigate the potential and mechanisms of cyclanoline (Cyc) in overcoming cisplatin
resistance.

Methods:

Cisplatin-resistant T24 and BIU-87 cell models (T24/DR and BIU-87/DR) were established by increasing
gradual concentration. Western Blot (WB) assessed the phosphorylation of STAT3, JAK2, and JAK3.
T24/DR and BIU-87/DR cell lines were treated with selective STAT3 phosphorylation modulators, and cell viability
was evaluated by CCK-8. Cells were subjected to cisplatin, Cyc, or their combination. Immunofluorescence
(IHC) examined p-STAT3 expression. Protein and mRNA levels of apoptosis-related and cell cycle-related factors
were measured. Changes in proliferation, invasion, migration, apoptosis, and cell cycle were monitored. In
vivo, subcutaneous tumor transplantation models in nude mice were established, assessing tumor volume and
weight. Changes in bladder cancer tissues were observed through HE staining, and the p-STAT3 was assessed via
WB and IHC.

Results:

Cisplatin-resistant cell lines were successfully established, demonstrating increased phosphorylation of
STAT3, JAK2, and JAK3. Cisplatin or Cyc treatment decreased p-STAT3, inhibited invasion and migration, and
induced apoptosis and cell cycle arrest in the G0/G1 phase in vitro. In vivo, tumor growth was significantly suppressed,
with extensive tumor cell death. IHC and WB consistently showed a substantial downregulation of
STAT3 phosphorylation. These changes were more pronounced when cisplatin and Cyc were administered in
combination.

Conclusion:

Cyc reverses cisplatin resistance via JAK/STAT3 inhibition in bladder cancer, offering a potential
clinical strategy to enhance cisplatin efficacy in treating bladder cancer.
A Novel Combinatorial Regimen Using Sorafenib and Uttroside B, A US FDA-designated ‘Orphan Drug’, for the Treatment of Hepatocellular Carcinoma
Authors: Keerthana Chenicheri Kizhakkeveettil , Aiswarya Sreekumar U. , Rayginia Tennyson P. , Vijayan Yadu , James Shirly , Shifana Sadiq C. , Sundaram Sankar , Induja D.K. , Lankalapalli Ravi S. , Harikumar Kuzhuvelil B. , Anto Ruby John
Published: August 2024

Introduction:

Sorafenib (Sor) is the first-line treatment option in clinics for treating advanced unresectable
hepatocellular carcinoma (HCC). However, acquired chemoresistance and adverse side effects associated
with Sor monotherapy limit its clinical benefits. We have previously reported the exceptional anti-HCC potential
of uttroside B (Utt-B), a furostanol saponin isolated in our lab from Solanum nigrum Linn. leaves. The current
study has evaluated the supremacy of a combinatorial regimen of Sor and Utt-B over Sor monotherapy.

Methods:

MTT assay was used for In vitro cytotoxicity studies. A clonogenic assay was conducted to assess the
anti-proliferative effect of the combination. Annexin V/PI staining, confocal microscopy, FACS cell cycle analysis,
and Western blotting experiments were performed to validate the pro-apoptotic potential of the combination
in HepG2 and Huh7 cell lines. Pharmacological safety evaluation was performed in Swiss albino mice.

Results:

Our results indicate that Utt-B augments Sor-induced cytotoxicity in HepG2 and Huh7 cells. The combination
inhibits the proliferation of liver cancer cells by inducing apoptosis through activation of the caspases 7
and 3, leading to PARP cleavage. Furthermore, the combination does not induce any acute toxicity in vivo, even
at a dose five times that of the effective therapeutic dose.

Conclusion:

Our results highlight the potential of Utt-B as an effective chemosensitizer, which can augment the
efficacy of Sor against HCC and circumvent Sor-induced toxic side effects. Moreover, this is the first and only
report to date on the chemosensitizing potential of Utt-B and the only report that demonstrates the therapeutic
efficacy and pharmacological safety of a novel combinatorial regimen involving Utt-B and Sor for combating
HCC.
Application of Nanoparticles in the Diagnosis and Treatment of Colorectal Cancer
Authors: Song Qiuyu , Zheng Yifeng , Zhong Guoqiang , Wang Shanping , He Chengcheng , Li Mingsong
Published: August 2024

:

Colorectal cancer is a common malignant tumor with high morbidity and mortality rates, imposing a
huge burden on both patients and the healthcare system. Traditional treatments such as surgery, chemotherapy
and radiotherapy have limitations, so finding more effective diagnostic and therapeutic tools is critical to improving
the survival and quality of life of colorectal cancer patients. While current tumor targeting research mainly
focuses on exploring the function and mechanism of molecular targets and screening for excellent drug targets, it
is crucial to test the efficacy and mechanism of tumor cell therapy that targets these molecular targets. Selecting
the appropriate drug carrier is a key step in effectively targeting tumor cells. In recent years, nanoparticles have
gained significant interest as gene carriers in the field of colorectal cancer diagnosis and treatment due to their
low toxicity and high protective properties. Nanoparticles, synthesized from natural or polymeric materials, are
NM-sized particles that offer advantages such as low toxicity, slow release, and protection of target genes during
delivery. By modifying nanoparticles, they can be targeted towards specific cells for efficient and safe targeting
of tumor cells. Numerous studies have demonstrated the safety, efficiency, and specificity of nanoparticles in targeting
tumor cells, making them a promising gene carrier for experimental and clinical studies. This paper aims to review
the current application of nanoparticles in colorectal cancer diagnosis and treatment to provide insights for
targeted therapy for colorectal cancer while also highlighting future prospects for nanoparticle development.