bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglia PTK2B/Pyk2 in the Pathogenesis of Alzheimer’s Disease
Authors: Guo Yun , Sun Cheng-Kun , Tang Lian , Tan Meng-Shan 
Published: February 2024

Abstract:
Alzheimer's disease (AD) is a highly hereditary disease with complex genetic susceptibility
factors. Extensive genome-wide association studies have established a distinct susceptibility
link between the protein tyrosine kinase 2β (PTK2B) gene and late-onset Alzheimer’s disease
(LOAD), but the specific pathogenic mechanisms remain incompletely understood. PTK2B is
known to be expressed in neurons, and recent research has revealed its more important significance
in microglia. Elucidating the role of PTK2B high expression in microglia in AD's progression
is crucial for uncovering novel pathogenic mechanisms of the disease. Our review of existing
studies suggests a close relationship between PTK2B/proline-rich tyrosine kinase 2 (Pyk2) and tau
pathology, and this process might be β-amyloid (Aβ) dependence. Pyk2 is hypothesized as a pivotal
target linking Aβ and tau pathologies. Concurrently, Aβ-activated Pyk2 participates in the regulation
of microglial activation and its proinflammatory functions. Consequently, it is reasonable to
presume that Pyk2 in microglia contributes to amyloid-induced tau pathology in AD via a neuroinflammatory
pathway. Furthermore, many things remain unclear, such as identifying the specific
pathways that lead to the release of downstream inflammatory factors due to PTK2B phosphorylation
and whether all types of inflammatory factors can activate neuronal kinase pathways. Additionally,
further in vivo experiments are essential to validate this hypothesized pathway. Considering
PTK2B/Pyk2's potential role in AD pathogenesis, targeting this pathway may offer innovative and
promising therapeutic approaches for AD.
Hybrid Nanoparticle for Co-delivering Paclitaxel and Dihydroartemisinin to Exhibit Synergic Anticancer Therapeutics
Authors: Tran Bao Ngoc , Ninh Thu Thi Kim , Do Thao Thi , Do Phuong Thi , Nguyen Chien Ngoc 
Published: February 2024

Aim:
Anticancer treatment is required to provide effective and safe patient medicines.
This research aided in developing and applying nanoparticles (NPs) for cancer treatment.

Background:
The poor solubility of paclitaxel (PTX) restricts its therapeutic efficacy because of
allergic side effects caused by formulation excipients. To overcome this, PTX was coupled with
artemisinin derivatives and loaded into an NP drug delivery system to enhance its effects while
addressing its low solubility.

Objectives:
This study prepared and characterized a hybrid PLGA-lecithin NP containing dihydroartemisinin
(DHA) and PTX for synergic anticancer therapy. A lyophilization study improved
the stability of the NP drug formulations.

Methods:
Dual PTX- and DHA-loaded PLGA- and lecithin-based NPs were prepared using a
single-step solvent evaporation method. The NP suspensions were lyophilized, and the types and
ratios of cryoprotectants were investigated. The physicochemical properties of NPs and lyophilized
cakes (Lyo-NPs) were characterized. The stability of the Lyo-NPs was investigated at 2-8°C
and room conditions. The anticancer effects of the drug combination, NP suspension, and lyophilized
powder were analyzed using an in vitro cytotoxicity assay and an in vivo model.

Results:
The optimal PTX-DHA loaded PLGA-lecithin-NP was formulated (200 nm, PDI: 0.248
± 0.003, Zeta potential: -33.60 ± 3.39 mV). Mannitol was selected for lyophilization. Lyo-NPs
improved the stability of the NPs (1 year), wherein the physicochemical properties of the NPs
were maintained (RDI was close to 1.0). An in-vitro cytotoxicity assay of PTX combined with
DHA showed a synergistic anticancer effect (CI <1.0). The suppressive effects of Lyo-NPs on
tumor growth in vivo were dose-dependent. While the cocktail of free drugs showed high toxicity
(7.5 mg PTX-15 mg DHA/kg) in-vivo, Lyo-NPs showed no statistical differences in hematological
and biochemical parameters compared to the control.

Conclusion:
Dual-drug-loaded hybrid PLGA-lecithin NP is a potential system to minimize severe
side effects while enhancing antitumor efficacy, in which lyophilization is a key process to
increase stability.
Nitrosamine Impurities in Pharmaceuticals: An Empirical Review of their
Detection, Mechanisms, and Regulatory Approaches
Authors: Bhirud Darshan , Agrawal Gyan , Shah Harshil , Patel Artiben , Palkar Mahesh B. , Bhattacharya Sankha , Prajapati Bhupendra G. 
Published: February 2024

Abstract:
Since their discovery in valsartan-containing drugs, nitrosamine impurities have
emerged as a significant safety problem in pharmaceutical products, prompting extensive recalls
and suspensions. Valsartan, candesartan, irbesartan, olmesartan, and other sartans have been discovered
to have additional nitrosamine impurities, such as N-nitroso-N-methyl-4-aminobutyric
acid (NMBA), N-nitroso-Di-isopropyl amine (NDIPA), N-nitroso-Ethyl-Isopropyl amine (NEIPA),
and N-nitroso-Diethyl amine (NDEA). Concerns about drug safety have grown in response
to reports of nitrosamine contamination in pharmaceuticals, such as pioglitazone, rifampin, rifapentine,
and varenicline. This review investigates the occurrence and impact of nitrosamine impurities
in sartans and pharmaceutical goods, as well as their underlying causes. The discussion
emphasizes the significance of comprehensive risk assessment and mitigation approaches at various
phases of medication development and manufacturing. The link between amines and nitrosamine
impurities is also investigated, with an emphasis on pH levels and the behaviour of primary,
secondary, tertiary, and quaternary amines. Regulations defining standards for nitrosamine
assessment and management, such as ICH Q3A-Q3E and ICH M7, are critical in resolving impurity
issues. Furthermore, the Global Substance Registration System (GSRS) is underlined as being
critical for information sharing and product safety in the pharmaceutical industry. The review specifically
focuses on the relationship between ranitidine and N-nitroso dimethyl amine (NDMA) in
the context of the implications of nitrosamine contamination on patient safety and medicine supply.
The importance of regulatory authorities in discovering and correcting nitrosamine impurities
is highlighted in order to improve patient safety, product quality, and life expectancy. Furthermore,
the significance of ongoing study and attention to nitrosamine-related repercussions for increasing
pharmaceutical safety and overall public health is emphasized.
Enhancing Drug-Target Binding Affinity Prediction through Deep Learning and Protein Secondary Structure Integration
Authors: Zhang Runhua , Zhu Baozhong , Jiang Tengsheng , Cui Zhiming , Wu Hongjie 
Published: February 2024

Background:
Conventional approaches to drug discovery are often characterized by
lengthy and costly processes. To expedite the discovery of new drugs, the integration of artificial
intelligence (AI) in predicting drug-target binding affinity (DTA) has emerged as a crucial approach. Despite the proliferation of deep learning methods for DTA prediction, many of these
methods primarily concentrate on the amino acid sequence of proteins. Yet, the interactions between drug compounds and targets occur within distinct segments within the protein structures,
whereas the primary sequence primarily captures global protein features. Consequently, it falls short
of fully elucidating the intricate relationship between drugs and their respective targets.

Objective:
This study aims to employ advanced deep-learning techniques to forecast DTA while incorporating information about the secondary structure of proteins.

Methods:
In our research, both the primary sequence of protein and the secondary structure of protein were leveraged for protein representation. While the primary sequence played the role of the
overarching feature, the secondary structure was employed as the localized feature. Convolutional
neural networks and graph neural networks were utilized to independently model the intricate features of target proteins and drug compounds. This approach enhanced our ability to capture drugtarget interactions more effectively

Results:
We have introduced a novel method for predicting DTA. In comparison to DeepDTA, our
approach demonstrates significant enhancements, achieving a 3.9% increase in the Concordance Index (CI) and a remarkable 34% reduction in Mean Squared Error (MSE) when evaluated on the KIBA dataset.

Conclusion:
In conclusion, our results unequivocally demonstrate that augmenting DTA prediction
with the inclusion of the protein's secondary structure as a localized feature yields significantly improved accuracy compared to relying solely on the primary structure.
The Use of the Titanium Tetrachloride (TiCl4) Catalysts as a Reagent for Organic Synthesis
Authors: Hudda Sharwan , Wadhwa Pankaj , Gupta Mukta , Chaudhary Manish , Lakhujani Lakhan 
Published: February 2024

:
TiCl4 is a widely utilized reagent in organic synthesis, often functioning through Lewis’s
acid-promoted transformations. This review explores the potential for TiCl4 to catalyse various examples,
adhering to the classic catalyst definition and allowing for the use of sub-stoichiometric
quantities of the catalyst relative to the substrate. The use of metal catalysts in organic synthesis
has witnessed a surge in interest due to their ability to facilitate a wide range of chemical reactions.
This review article highlights the significance of titanium metal catalysts via comparison with other
metal catalysts like Pd (NO3)2, IrO4, Au/Fe2O3, SnCl2, and AlCl3. Among these catalysts, titanium
tetrachloride (TiCl4) has gained considerable popularity for its cost-effectiveness, eco-friendliness,
enhancing reaction efficiency, and ability to accelerate reactions while reducing reaction times. This
comparison helps in determining the most suitable catalyst for different chemical processes, considering
efficiency, safety, and economic factors. TiCl4 operates as a non-consumable catalyst, allowing
for the use of sub-stoichiometric quantities relative to the substrate.

:
This review discusses TiCl4's applications, efficiency, and mechanisms in organic synthesis. It
distinguishes itself by presenting new applications and comparative efficiencies of TiCl4, delving
into detailed reaction mechanisms, and discussing its environmental, economic, and safety aspects.
TiCl4's role in pivotal chemical reactions, such as Friedel-Crafts acylation and alkylation, epoxidation,
cyclization, Mannich reactions, Suzuki-Miyaura reactions, Pechmann condensation,
Knoevenagel condensation, anti-Markovnikov hydration, pinacol coupling, and Diels-Alder reactions.
These reactions have led to the synthesis of biologically active compounds like zolmitriptan,
ropinirole, risperidone, and rivastigmine. TiCl4-catalyzed reactions are characterized by their mild
conditions, high efficiency, and selectivity, making them an attractive choice for modern organic
cyclic, acyclic, and heterocyclic synthesis.
Women’s Participation in Training on The Processing of Economic Value Rubber Seeds and Local Wisdom Based in Curahtakir Village, Jember
Authors: NurSekti Marita , Sepiarti Serafin Wisni 
Published: February 2024

Curahtakir Village, located in Jember, is affiliated with PTPN XII and serves as a prominent rubber-producing community. A significant proportion of the village's population comprises women who are actively engaged in rubber-related labor. A significant quantity of rubber seeds is discarded and commercially traded at a price range of IDR 2000-3000 per kilogram. The absence of sufficient knowledge regarding the local potential necessitates the provision of training programs focused on the conversion of rubber seeds into high-value food products. The rubber seed chip products have the potential to enhance the local wisdom of Curahtakir Village. This research explains women's participation, empowerment through training for women, and training based on local wisdom. The study involved conducting interviews with female rubber workers, trainees, and members of the local community. The village chiefs serve as supplementary sources of information to obtain insights on the involvement of women in training programs. The findings indicated a significant level of active participation among women. During the pre-planning, the activities aimed at promoting women's participation persist in their planning and evaluation, despite encountering various obstacles, such as the challenges posed by their existing work commitments. The implementation continued to run well, the participants continued to follow the activity process to completion.
Status and Influencing Factors of Social Media Addiction in Chinese Workers: Cross-Sectional Survey Study
Authors: Kong Weitao , Li Yuanyuan , Luo Aijing , Xie Wenzhao 
Published: February 2024

Background
Social media addiction (SMA) caused by excessive dependence on social media is becoming a global problem. At present, most of the SMA studies recruit college students as research participants, with very few studies involving workers and other age groups, especially in China.

Objective
This study aims to investigate the current status of SMA among Chinese workers and analyze its influencing factors.

Methods
From November 1, 2022, to January 30, 2023, we conducted an anonymous web-based questionnaire survey in mainland China, and a total of 5176 participants completed the questionnaire. The questionnaire included the Social Networking Service Addiction Scale, Maslach Burnout Inventory–General Survey scale, Mindful Attention Awareness Scale, as well as questionnaires regarding participants’ social media use habits and demographic information.

Results
Through strict screening, 3468 valid questionnaires were included in this study. The main findings of this study revealed the following: the average SMA score of workers was higher (mean 53.19, SD 12.04), and some of them (393/3468, 11.33%) relied heavily on social media; there were statistically significant differences in SMA scores among workers in different industries (F14,3453=3.98; P<.001); single workers (t3106=8.6; P<.001) and workers in a relationship (t2749=5.67; P<.001) had higher SMA scores than married workers, but some married workers (214/3468, 6.17%) were highly dependent on social media; the level of SMA among female workers was higher than that of male workers (t3466=3.65; P<.001), and the SMA score of workers negatively correlated with age (r=−0.22; P<.001) and positively correlated with education level (r=0.12; P<.001); the frequency of using social media for entertainment during work (r=0.33; P<.001) and the frequency of staying up late using social media (r=0.14; P<.001) were positively correlated with the level of SMA in workers; and the level of SMA in workers was significantly positively correlated with their level of burnout (r=0.35; P<.001), whereas it was significantly negatively correlated with their level of mindfulness (r=−0.55; P<.001).

Conclusions
The results of this study suggest that SMA among Chinese workers is relatively serious and that the SMA problem among workers requires more attention from society and academia. In particular, female workers, young workers, unmarried workers, highly educated workers, workers with bad social media habits, workers with high levels of job burnout, and workers with low levels of mindfulness were highly dependent on social media. In addition, occupation is an important influencing factor in SMA. Thus, the government should strengthen the supervision of social media companies. Medical institutions should provide health education on SMA and offer intervention programs for those addicted to social media. Workers should cultivate healthy habits while using social media.
Evaluación del desempeño docente en los cursos de especializaciones médicas de la Facultad de Medicina de la UNAM en el Hospital General “Dr. Manuel Gea González”
Authors: Martínez-González Adrián , Sierra-Martínez Octavio , García Durán Rocío , Salazar Valadez Alberto , Morales López Sara , Valenzuela Romero Rita , Sánchez Mendiola Melchor 
Published: February 2024

Introducción: Ser especialista clínico o investigador no garantiza ser un buen docente ya que además de ser experto en un campo disciplinario, se requieren otras funciones y actividades que pueden evaluarse y mostrar con ello los diferentes grados de desempeño para perfeccionar el proceso educativo.
Objetivo: Evaluar los diversos grados de desempeño docente según la opinión de los residentes en el Hospital “Dr. Manuel Gea González”.
Métodos: La población de estudio estuvo constituida por los profesores del mencionado hospital. Las variables consideradas fueron edad, género, año de residencia y especialidades clasificadas en Médicas y Quirúrgicas. El cuestionario anónimo de evaluación del desempeño docente por opinión del residente tiene evidencia de validez y confiabilidad; está integrado por 37 enunciados y cinco dimensiones con una escala de respuesta tipo Likert.
Resultados: Se evaluaron 25 profesores de 13 especialidades por parte de 281 residentes quienes opinaron que el desempeño docente es aceptable, con una media de 4.25 para las especialidades médicas y excelente con una media de 4.70 para las quirúrgicas. La dimensión mejor valorada fue conocimiento de la materia con una media de 4.32 en contraste con la dimensión de evaluación con 3.84. Cabe destacar que las puntuaciones de las especialidades quirúrgicas fueron mayores estadísticamente en cuatro de las cinco dimensiones en comparación con las médicas (ANOVA), con excepción de la dimensión I que hace referencia a la relación profesor-residente y motivación.
Conclusiones: La planta académica del hospital fue valorada por la opinión de los residentes como aceptable. Se encontraron diversos grados de desempeño docente que oscilaron entre suficiente y aceptable hasta excelente. Las especializaciones quirúrgicas fueron mejor valoradas en comparación con las médicas.
La eterna batalla contra la Ley de Murphy (y sus corolarios)
Authors: Sánchez-Mendiola Melchor 
Published: February 2024

Ley de Murphy: Si algo puede salir mal, saldrá malDos corolarios de la Ley de Murphy:Nada es tan fácil como parece.
Todo lleva más tiempo del que usted piensa En este universo probabilístico, es prácticamente una certeza que todos nosotros en algún momento de nuestra vida hayamos sido víctimas de la Ley de Murphy, y que nos hayamos topado con alguno de sus corolarios. ¿Recuerda cuando se prometió a sí mismo, como uno de los propósitos de año nuevo, que terminaría de escribir el manuscrito para enviar a una revista antes de aceptar otro encargo académico?, ¿a cuántos de nosotros (me incluyo explícitamente) nos han ganado los múltiples compromisos, “emergencias” y “pendientes” (como los que ingeniosamente nos narran en los anuncios recientes del Instituto Federal Electoral), que forman parte de esa confabulación cósmica que evita que terminemos de escribir, revisar y enviar oportunamente a publicación los manuscritos que tenemos en el “tintero mental” de nuestras cabezas?
El aprendizaje complejo: Desafío a la educación superior
Authors: Castañeda-Figueiras Sandra , Peñalosa-Castro Eduardo , Austria-Corrales Fernando 
Published: February 2024

ResumenSe argumenta la necesidad de reformar estructuras y formas de organización en las universidades nacionales, para adecuarlas a los retos de un mundo cambiante donde el desarrollo en ciencia y tecnología, tanto como el acceso y distribución de la información vía Internet, impactan ya la formación del capital humano y exigen que la oferta universitaria sea de mano de obra, cada vez más calificada. A partir de la revisión del constructo “Aprendizaje Complejo”, se ofrece una perspectiva global sobre sus componentes principales y, a manera de ilustración, se presenta un trabajo empírico nacional que modeló estructuralmente mecanismos cognitivos (creencias y estrategias cognitivas) y autorregulatorios (atribucionales y motivacionales), de variables del aprendiz, del contenido y del contexto (presencia o virtual), que configuraron la formación psicológica teórica en estudio. Los resultados mostraron que el aprendizaje fue generado por complejas interacciones entre estas variables donde: la ejecución de los estudiantes no exitosos fue predicha por creencias epistemológicas ingenuas y estrategias cognitivo-autorregulatorias deficientes. en cambio, la de los estudiantes exitosos lo fue por estrategias autorregulatorias y cognitivas estratégicas, que le permiten al estudiante ser el “agente activo” de su propio conocimiento, así como por creencias epistemológicas reflexivas sobre el conocimiento y la manera como se está aprendiendo. En relación con contexto de entrega de la instrucción, se confirmó que el aprendizaje es influido más por el método instruccional utilizado, que por el contexto presencial o virtual utilizado. Los efectos de la interacción contenido-contexto mostraron más y mejor aprendizaje cuando los estudiantes usaron estrategias autorregulatorias referidas a la persona en el contexto presencial, y de autorregulación de materiales para el contexto virtual. Además, se identificó una tendencia en la que contenidos perceptuales fueron mejor aprendidos en línea. Con esta base, se discuten implicaciones de este tipo de investigación a otras disciplinas profesionales.
<p>LA REPRESENTACIÓN SOCIOLINGÜÍSTICA DE LOS ANDALUCES EN "ALLÍ ABAJO"</p>
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Authors: GÁLVEZ FORTE Carmen 
Published: February 2024

La ficción española ha llevado en variadas ocasiones a la pequeña y gran pantalla la figura del personaje andaluz. Sobre Andalucía y los andaluces a lo largo de los siglos se han vertido una serie de prejuicios por su modo de hablar y por su manera de vivir. Algunas veces, dichos prejuicios se han estereotipado, llegando a desprestigiar al andaluz.
En el presente trabajo se realizará un estudio sobre la variedad andaluza, las actitudes y creencias lingüísticas, además de examinar la figura del andaluz en el cine. A continuación, se realizará un análisis de cuatro escenas de la serie de Atresplayer, Allí abajo, donde se representan variados estereotipos que giran en torno a la figura del andaluz, además de los prejuicios que los vascos suelen tener sobre los andaluces.