bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the clinical efficacy of therapies in patients with symptoms of gastroesophageal reflux disease after phenotyping based on 24-h pH-impedance monitoring
Authors: Maev I. V. , Ovsepian M. A. , Andreev D. N. , Barkalova E. V. , Shaburov R. I. , Tararina L. A.
Published: October 2024

Introduction. The inefficiency of proton pump inhibitors (PPIs) in patients with symptoms of gastroesophageal reflux disease (GERD) may be caused by functional esophageal diseases, which should be diagnosed by using pH-impedance monitoring.

Aim. To evaluate the clinical efficacy of therapies in patients with symptoms of gastroesophageal reflux disease after phenotyping based on 24-h pH-impedance monitoring.

Materials and methods. A total of 61 patients with GERD symptoms were observed in a prospective study. The patients were categorized into 3 phenotypes based on the Lyon Consensus 2.0 and Rome criteria IV: nonerosive reflux disease (NERD), hypersensitive esophagus (HSE), functional heartburn (FH). The 5-point Likert scale was used to measure the severity of symptoms. NERD patients received PPI (omeprazole 20 mg twice daily), HSE patients received PPI (omeprazole 20 mg twice daily) and a selective serotonin reuptake inhibitor (SSRI) (citalopram 20 mg daily), FH patients received tricyclic antidepressant (TCA) (amitriptyline ¼ tablet at the bedtime). The entire length of treatment in all groups was 4 weeks.

Results. The severity of heartburn in patients with NERD, HSE and FH before treatment averaged 3.23 (95% CI 3.02–3.43) points on the Likert scale (strong). Due to therapy, the average score in the NERD group decreased from 3.48 (95% CI 3.23–3.74) to 0.77 (95% CI 0.53–1.01), in the HSE group from 2.92 (95% CI 2.41–3.42) to 0.83 (95% CI 0.30–1.36), and in the FH group from 2.86 (95% CI 2.41–3.30) to 0.86 (95% CI 0.41–1.30). The efficacy of therapy in NERD patients was 85%. The efficacy of PPI + SSRI and TCA in patients with HSE and FH was 83% and 79%, respectively.

Conclusion. A differentiated approach to the treatment of patients with heartburn symptoms based on phenotyping using 24-h impedance-pH findings can help optimize the therapy and improve its efficiency.
Irritable bowel syndrome: different approaches to therapy
Authors: Minushkin O. N.
Published: October 2024

This article provides present-date knowledge on irritable bowel syndrome (IBS) and different approaches to therapy. The method of presenting the materials is based on a specific clinical case, which includes the diagnostic algorithm, a list of modern medicines, defines pharmacological targets and, based on them, describes an approach to the selection of an adequate pharmaceutical drug. In the presented case, patient S. (37 years old) had a functional bowel disorder (stool disorder) for seven years, and short-term pharmacotherapy courses did not produce a lasting effect. The course of the disease had become more alarming over time. The medical examination confirmed irritable bowel syndrome (IBS) in the patient – a mixed variant with pain syndrome during exacerbations. The drug of choice was otilonium bromide, an intestinal antispasmodic, which differed from other intestinal antispasmodics in its complex mechanism of action and practically zero absorption (3%). It allowed for a long-term therapy reducing a risk of side effects. The duration of treatment was 15 weeks (40 mg 3 times a day), of which the last three weeks were regarded as the maintenance therapy at a dose of 40 mg once a day. Pain and dysbiosis were completely relieved at 4 weeks of treatment. Motility and stool were restored, which resulted in the improvement of the quality of life and the symptoms of anxiety were resolved almost completely after 12 weeks of treatment. Thus, otilonium bromide had an effect on all pharmacological targets that were established before treatment.
Gastrointestinal symptoms in children with mastocytosis
Authors: Kasikhina E. I. , Nada A. Ya. , Zhukova O. V. , Ostretsova M. N.
Published: October 2024

Introduction. Mastocytosis is a heterogeneous group of diseases characterized by the abnormal accumulation of clonal mast cells (MCs) in various tissues and organs, including skin, bone marrow, liver, spleen and lymph nodes. The clinical picture of cutaneous and indolent systemic mastocytosis is formed by a wide range of symptoms associated with activation of mast cells. Single European studies have demonstrated wide variability in the frequency of gastrointestinal symptoms (GI-symptoms)) in children with mastocytosis (from 15 to 50%).

Aim. To analyze the frequency of mediator-related GI-symptoms in children with different subtypes and clinical forms of mastocytosis.

Materials and methods. A prospective observational study included data from 289 children aged 3 to 17 years who were under observation at the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology. Symptoms were assessed using the Pediatric grade scale of symptoms of mastocytosis. Clinical manifestations of reactions caused by mast cell degranulation were compared with data from clinical and laboratory studies. The concentrations of tryptase and histamine in the blood serum of patients were determined. The incidence of organomegaly and mesenteric lymphadenitis in children with mediating symptoms and without symptoms was determined using ultrasound.

Results. 67 (23.2%) patients had GI symptoms. More than half of the patients (51.6%) indicated abdominal pain, 32.3% reported diarrhea. The severity of pain symptoms correlated with the level of serum tryptase (ρ = 0.564, p < 0.01). The incidence of hepatomegaly and mesadenitis in children with GI- symptoms was 19.4% and 25.4%, respectively. In a comparative analysis in groups of children with and without GI symptoms, the differences in the number of identified cases of organomegaly and mesadenitis were statistically significant (p < 0.001). An increase in histamine levels in the blood was detected in half of the patients with complaints of heartburn and nausea.

Conclusion. Our results demonstrated that a study of the level of serum tryptase, ultrasound of the abdominal organs and lymph nodes should be carried out in all children with mediator-related GI-symptoms regardless of the clinical form of mastocytosis.
Desenvolvimento de modelo multicritério construtivista para gestão do desempenho: Estudo de caso na COAUD/MP/SC
Authors: Petri Sérgio Murilo , Lisboa Felipe Veck
Published: October 2024

Objetivo da pesquisa construir um modelo multicritério construtivista de avaliação de desempenho para apoiar a gestão da COAUD/MPSC. Utilizou-se como instrumento de intervenção, a Metodologia Multicritério de Apoio à Decisão-Construtivista (MCDA-C). Após a realização de entrevistas semiestruturadas com os servidores da coordenadoria, foram identificados 80 Elementos Primários de Avaliação, os quais serviram de base para a construção de 136 conceitos. Os conceitos foram agrupados em 7 áreas de preocupação. Com o intuito de expandir o conhecimento do decisor, foram elaborados os mapas cognitivos de cada área. Foram construídos 70 descritores, com a definição do nível bom e neutro. Com a estruturação do modelo finalizada, foi realizada avaliação do desempenho da Coordenadoria, a partir da construção das funções de valor e da identificação das taxas de compensação. Verificou-se que o desempenho da COAUD foi de 17 pontos. Com o intuito de aprimorar a gestão, foram elaboradas cinco sugestões de melhorias, que, se aplicadas, permitiriam que o perfil de desempenho da COAUD fosse elevado para 37 pontos. Por fim foi realizado o cotejamento dos indicadores construídos neste estudo com os encontrados em outras pesquisas. Verificou-se reduzida similaridades entre os indicadores utilizados na literatura com os elaborados nessa pesquisa. Espera-se que com o a implementação do modelo a COAUD aprimore a sua gestão, aumentando o rol de atividades desempenhadas, priorizando aquelas consideradas essenciais e que não estão nos níveis de performance esperadas pelo decisor e auxiliando as demais áreas da Instituição nas suas atividades e, deste modo, torne a gestão do órgão mais eficiente.
A második karriert kezdő tanárok identitáskonstrukciós dilemmái és támogatásának lehetőségei
Authors: Rapos Nóra , Nagy Krisztina , Takácsné Kárász Judit , Péter Petra , Szilvási Csenge
Published: October 2024

A tanárhiány nemcsak hazánkban, hanem Európa számos országában komoly problémát jelent, amelyre az egyes régiók eltérő megoldási utakat dolgoztak ki. Ilyen alternatív út a más szakmában munkatapasztalattal rendelkező, felnőtt tanulók tanári pályára állásának támogatása. Kritikai, feltáró, narratív irodalmi áttekintésű (N=97) tanulmányunkban értelmezzük és elemezzük a második karriert kezdő tanárok (second career teacher (SCT)) szakmai tanulását és identitáskonstrukcióját és az azokat meghatározó személyes tényezőket, annak érdekében, hogy azonosíthassuk a tipikus feszültségeket ebben a komplex, dinamikus folyamatban. A feszültségek – melyek támogatják vagy gátolják az identitásalakulást – Kaplan és Garner (2017) szerepidentitás modellje alapján kerülnek elemzésre. Ezek az önészlelés és az önmeghatározás, az ontológiai és az episztemológiai elképzelések, a tervek és az elképzelések, valamint az észlelt cselekvési lehetőségek. Megállapítottuk többek között azt, hogy a tanításról vallott tanárfókuszú gondolkodás gyakorta okozhat feszültséget az SCT-k esetében, illetve hogy az erős belső elkötelezettség, valamint a tanítás valós világával való szembesülés gyakran válik feszültség forrásává. A SCT-k lemorzsolódásának megelőzése indokolttá teszi a képzés, valamint a tanulási környezet optimális jellemzőinek azonosítását. Az elemzett írások alapján ezek a következők: a hallgatói sajátosságok értelmezésére épülő tervezés, a rugalmasság és a felnőttkori szakmatanulás sajátosságainak tudatos kezelése.
Synthesis, Antileishmanial Activity, and in silico Study of 2-Hydroxy-3-(1,2,3-triazolyl)propyl Vanillin Derivatives
Authors: S. Santiago Samira , S. Freitas Camila , V. Costa Adilson , B. de Oliveira Mariana , F. C. Faria Aidene , S. Belarmino William , F. Moura Gisely , A. dos Santos Nayara , Romão Wanderson , Lacerda Júnior Valdemar , M. de Oliveira Fabrício , V. Oliveira Osmair , A. F. Coelho Eduardo , R. Teixeira Róbson
Published: October 2024

This study details the preparation, antileishmanial assay, and in silico analysis of twenty 2-hydroxy-3-(1,2,3-triazolyl)propyl vanillin derivatives. These compounds were synthesized in three steps and evaluated against Leishmania infantum, Leishmania amazonensis, and Leishmania braziliensis promastigotes. Compounds 3s and 3t were the most effective, showing good activity against all Leishmania species tested. Molecular docking indicated that all compounds bind favorably to the sterol 14α-demethylase (CYP51) enzyme from L. infantum. ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis indicated good oral bioavailability, non-blood-brain barrier penetration, and high gastrointestinal absorption. Posaconazole and compounds 3e, 3s, and 3t remained stable in the CYP51 binding region during 100 ns molecular dynamics (MD) simulations. Root mean square deviation (RMSD) and root mean square fluctuations (RMSF) analyses from the MD trajectory revealed significant conformational fluctuations of the CYP51 N-terminal, suggesting occasional expulsion of 3e, potentially explaining its higher IC50 (half-maximal inhibitory concentration) values. Pairwise decomposition analyses from molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations highlighted the importance of hydrophobic residues in interacting with the synthesized derivatives.
Seismic resistance analysis and optimization of gymnasium truss structure
Authors: Wang Chunxiang , Li Wencheng , Zhao Yue
Published: October 2024

The gymnasium is mainly composed of truss structure, with a large span, and requires high seismic performance. To ensure greater stability of the truss structure, modal analysis was conducted on the mechanical model, yielding the natural frequencies and modal shapes. In order to improve the seismic performance, BRB rods were added to the support points, and the frame structure was reinforced with diagonal braces. Through modal verification, it can be seen that the stiffness of the truss structure was significantly improved. The internal forces of the truss were simulated under the El Centro and Taft seismic wave conditions. The results show that the optimized structure can significantly reduce the internal forces and improve the overall seismic performance. The fundamental natural period of the reinforced structure is less than that of the unreinforced structure, and the stiffness of the reinforced steel structure increases, making it more sensitive to vertical seismic motion.
Design of monitoring system for material vibration screening equipment
Authors: Wang Juan , Sun Hao
Published: October 2024

In order to effectively reduce the failure rate of vibrating screens, a vibration monitoring system design was proposed based on the structure and working principle. The system should be able to monitor the operating state of the vibrating screen in real time, including vibration amplitude, frequency, axial displacement, etc., and be able to detect abnormal conditions in time and give warning prompts. The key hardware of the monitoring system was designed, including acceleration sensor, power module, signal filtering circuit, etc. The sensitivity of the acceleration sensor was measured using comparative method and accurately completed parameter calibration. The eccentric block was used to simulate different deviation of excitation force for system vibration signal test and calibration. The results show that under normal operating conditions, the amplitude of each frequency of the vibrating screen is less than 0.04 g. Under the condition of excitation force deviation, the amplitude of 16 Hz is obviously lower than that of other frequencies, which means that the vibrating screen is currently experiencing lateral oscillation.
Analysis and optimization of abnormal noise in lubricating oil circuit of diesel engine
Authors: Tang Yongwei , Wu Lianmao , Gong Xiaoping , Chen Jingchang , Chen Zhao , Su Hongjian , Ren Lei , Zhang Tao
Published: October 2024

Engine abnormal noise is one of the common engine faults, which will affect the comfort, power and safety of the automobile at the same time. In order to study the abnormal noise existing in the test process of diesel engine lubricating oil circuit system, 1D numerical simulation analysis of its flow field is carried out by using simulation software GT-power to verify the boundary conditions of the model and analyze the fluctuation of pressure at different speeds and temperatures. Through numerical analysis, it is found that there is almost no pressure fluctuation in the lubrication system before the pressure limiting valve is opened, but after the pressure limiting valve is opened, pressure fluctuation occurs in the pipeline, and the pressure fluctuation is different at different positions. Finally, the lubrication pipeline is simulated and analyzed by Pumplinx software, and the pressure fluctuation in the lubrication pipeline of diesel engine is reduced by optimizing the diameter of the oil pipeline and increasing the cavity structure.
Seismic isolation design of high-rise shear wall structures in high-intensity areas
Authors: Li Shufeng , Du Shuting , Zhang Zhihui , Zhu Weijie
Published: October 2024

Taking a shear wall structure in a high-intensity area of 20 floors as an example, the seismic reduction scheme of the structure was determined, and the Etabs software was used to conduct time history analysis on the seismic and non-seismic structures. The floor shear force, overturning moment, and short-term surface pressure of the isolation support were obtained. The results showed that under frequent earthquake action, the average maximum floor shear force in the X direction of the isolated upper structure was only about 28 % of that of the non-isolated structure. The maximum inter story shear ratio was 0.34, and the maximum floor shear force in the Y direction was only about 25 % of that of the non-isolated structure. The maximum inter story shear ratio was 0.31. The average maximum overturning moment of the upper structure in the X direction after isolation is about 30 % of that of the non-isolated structure. The maximum overturning moment ratio is 0.36, and the average overturning moment of the maximum floor in the Y direction is about 22 % of that of the non-isolated structure. The maximum overturning moment ratio is 0.26. Under rare earthquake action, the maximum inter story displacement angles in the X and Y directions of each floor of the seismic isolation structure are 1/302 and 1/446, respectively. The maximum surface pressure value of the isolation bearing under rare earthquake is 28.9 MPa, the minimum surface pressure value is 5.58 MPa, and the maximum displacement is 579 mm, which meets the requirements of the specifications. Overall, the seismic performance of the seismic isolation structure is good, and the isolation scheme is feasible.
Modal analysis of key components of crusher based on digital simulation technology
Authors: Yao Yanna , Li Yaqing
Published: October 2024

The modal characteristics of the crusher rotor and shell constitute the crucial factors influencing vibration and noise. Based on the principle of simplification, the rotor component model was established. Through mesh optimization, the model accuracy and calculation efficiency can be ensured, and the calculation of natural frequency and modal shapes was completed based on ANSYS. To verify the accuracy of the finite element model, the modal test was carried out by the hammering method. Sensors were set in three different directions to obtain the frequency response function and the modal assurance criterion matrix mode confidence criterion. Using the same research method, the modal characteristics of the shell model were simulated and analyzed. The research results show that the modal parameters identified by the modal test are basically consistent with the simulation model. The natural frequencies of the rotor and the shell are quite different from the excitation frequency of the motor, and resonance problems will not occur when the crusher is proper functioning.
Groundwater potential zone mapping of Llandrindod Wells, Wales, UK using GIS, remote sensing, and analytic hierarchy process
Authors: Kareem Hayder H.
Published: October 2024

Groundwater is crucial for urban and rural water systems, especially as demand increases from climate change and population growth. This study addresses a gap in previous research on Groundwater Potential Zones (GWPZ). Drainage density, rainfall, slope, land use/land cover (LULC), soil, and geology, along with elevation were analyzed using ArcGIS and Remote Sensing with a weighted overlay method. GWPZs for Liandrindod Wells Watershed, Wales, UK is mapped using Multi-Criteria Analysis and Analytical Hierarchical Processing. Rainfall amounts range from very low (70–92 mm to very high (127–141 mm). The slope ranges from 0 to 195 degrees, with low slopes indicating high groundwater potential and high slopes indicating low potential. The LULC forming the region were water land, built-up area, cropland, rangeland, and treeland. The sub-basin soil falls into four distinct types: loam, sandy loam, sandy clay loam, and clay loam. The majority of the sub-basin is covered by rocks from the Silurian and Devonian periods. The following five zones make up the GWPZ map: Very High (147.7 km2) (2.9%), High (1943.4 km2) (38.3%), Moderate (2318.7 km2) (45.7%), Low (662.2 km2) (13%), and Very Low (4 km2) (0.08%). Groundwater-rich regions comprise about 87% of the study area.
Integrative Analysis Reveals Differential Characteristics of DDR1 Mutant and Wild-type Gastric Cancers and Constructs their Prediction Models
Authors: Tian Yonggang , Xie Yunqian , Yi Guirong , Yu FuBing , Bai Feihu , Wang Jun , Zhang Dekui
Published: October 2024

Introduction:

The molecular typing of gastric cancer by TCGA is significant
for the precision treatment of gastric cancer. However, the molecular typing of gastric
cancer by TCGA lacks the typing of the rare gene DDR1. Therefore, this study aimed to
integrate the analysis to reveal the differential features of DDR1 mutant and wild-type
gastric cancers and construct their prediction models.

Methods:

RNAseq data from 375 gastric cancer patients were downloaded from the TCGA
database to comprehensively compare the differences between mutant DDR1 and
wild-type DDR1 gastric cancers and construct a prognostic model for wild-type DDR1
gastric cancer.

Results:

First, the mutation rate of DDR1 in gastric cancer was 3.23%. Second, the upregulated
genes of mutant DDR1 gastric cancer were different from those of wild-type
DDR1 gastric cancer in terms of KEGG and GO enrichment. Next, both mutant DDR1
gastric cancers and wild-type DDR1 gastric cancers were associated with EPIC scores
and tumour stemness in macrophages. In addition, mutant DDR1 gastric cancers were associated
with the iron death-related genes RPL8, CS, and FANCD2 and the m6A-related
gene RBM15, compared with wild-type DDR1 gastric cancers. Finally, the established
LASSO regression model confirmed that the survival rate of the high-risk group of wild--
type DDR1 gastric cancer would be lower than that of the low-risk group.

Conclusion:

This study may provide a new molecular typing method for gastric cancer
by comparing the differences between mutant DDR1 and wild-type DDR1 gastric cancer.
Exploring the Dual Role of MALAT1 in Thyroid Tumorigenesis: Oncogenic or Tumor Suppressor?
Authors: Anbiyaee Omid , Ghaedrahmati Farhoodeh , Mousavi Salehi Abdolah , Khodadadi Ali , Kempisty Bartosz , Farzaneh Maryam , Dari Mahrokh Abouali Gale
Published: October 2024

Thyroid cancer is the most prevalent form of endocrine cancer. Therefore,
the administration of new therapeutic agents for thyroid cancer patients is necessary.
One of the recent successes in thyroid cancer research is the identification of the role
of signaling pathways in the pathogenesis of the disease. Emerging evidence reveals
that long non-coding RNAs (lncRNAs) can serve as novel therapeutic approaches for
the diagnosis and treatment of thyroid cancer. The lncRNA metastasis-associated lung
adenocarcinoma transcript-1 (MALAT1) plays key roles in gene expression, RNA
processing, and epigenetic regulation. It is believed that MALAT1 can regulate several
cancer-related processes, including tumour cell growth, proliferation, and metastasis.
MALAT1 is involved in the pathogenesis of thzroid cancers by targeting multiple
downstream targets and miRNA/mRNA axes. Here, we summarize the emerging roles
of MALAT1 in this cancer.
Prevalence and Associated Factors of Central Sensitization in Patients with Chronic Inflammatory Rheumatic Disease
Authors: Berrichi Imane , Taik Fatima Zahrae , Haddani Fouzia , Soba Nabil , Fourtassi Maryam , Abourazzak Fatima Ezzahra
Published: October 2024

Objective:

Despite advances in the treatment of Chronic Inflammatory Rheumatic Disease
(CIRD), pain remains a significant burden for patients and doctors. This study explored the
prevalence and associated factors of central sensitization (CS) in patients with CIRD.

Methods:

This is a cross-sectional study that included patients with CIRD followed at the University
Hospital Center in Tangier. Sociodemographic and clinical data were collected. Nociceptive
pain was assessed by the Visual Analogue Scale (VAS), disease activity by DAS-28 and ASDAS,
and CS by the validated Moroccan version of the Central Sensitization Inventory part A (CSI-A).
The Pain Catastrophizing Scale (PCS) was used to assess pain-related catastrophic thoughts, and
the PHQ-9 (Pain Health Questionnaire) was used to determine the severity of depressive symptoms.

Results:

We included 189 patients; 107 (56.61%) had rheumatoid arthritis. The median duration
of evolution of CIRD was 8 years, and the mean age was 47.49 ± 13.70 years, and 75.7% were women.
The mean pain VAS was 4.77+-2.76, and 37.6% of patients were in remission. The mean
central sensitization score was 37.42+- 16.75, with 44.9% having a CSI score≥40. In univariate
and multivariate analysis, our study showed that central sensitization is associated with pain severity
(β = 1.945(0.050-1.916), p = 0.039) and depression (β = 1.790(1.221-2.154), p ≤0.001)(8). A
statistically significant correlation was found between the CSI-A score and pain VAS (r = 0.32, p
<0.001).

Conclusion:

Our study showed that almost half of our patients with CIRD had CS. The main factors
associated with CS in our patients were pain severity and depression. We also found a significant
correlation between pain VAS and CSI.
Berberine Ameliorates High-fat-induced Insulin Resistance in HepG2 Cells by Modulating PPARs Signaling Pathway
Authors: Zhang Lingxiao , Yang Chenghao , Ding Xinyue , Zhang Hui , Luan Yuling , Tang Yueer , Liu Zongjun
Published: October 2024

Background:

Berberine (BBR), also known as berberine hydrochloride, was isolated
from the rhizomes of the Coptis chinensis. Studies have reported that BBR plays an important role
in glycolipid metabolism, including insulin (IR). The targets, and molecular mechanisms of BBR
against hyperlipid-induced IR is worthy to be further studied.

Material and Methods:

The related targets of BBR were identified via Pharmmapper database
and relevant targets of diabetes were obtained through GeneCards and Online Mendelian Inheritance
in Man (OMIM) database. The common targets were employed with the STRING database
and visualized with the protein-protein interactions (PPI) network. Gene Ontology (GO) and Kyoto
Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to explore
the biological progress and pathways. In vitro, human hepatocellular carcinomas (HepG2) cell
was used as experimental cell line, and an insulin resistant HepG2 cell model (IR-HepG2) was
constructed using free fatty acid induction. After intervention with BBR, glucose consumption
and uptake in HepG2 cells were observed. Molecular docking was used to test the interaction between
BBR and key targets, and real-time fluorescence quantitative PCR was used to detect the
regulatory effect of BBR on related targets.

Results:

262 overlapped targets were extracted from BBR and diabetes. In the KEGG enrichment
analysis, the peroxisome proliferator activated receptor (PPAR) signaling pathway was included.
In vitro experiments, BBR can significantly increase sugar consumption and uptake in IR HepG2
cells, while PPAR inhibitors can weaken the effect of BBR on IR-HepG2.

Conclusion:

The PPAR signaling pathway is one of the important pathways for BBR to improve
high-fat-induced insulin resistance in HepG2 cells.

conclusion:

The PPAR signaling pathway is one of the important pathways for BBR to improve high-fat induced insulin resistance in HepG2 cells.
Novel Pharmaceutical Interventions for Drug Targeting in Parkinson’s Disease
Authors: Chaurasia Simran , Dogra Sakshi Sharma , Hussain Md Sadique , Kumar Rajesh , Khurana Navneet
Published: October 2024

Parkinson's Disease (PD) presents as a neurodegenerative disorder characterized by a gradual
decline in brain function, typically advancing slowly over time in most individuals. However, as
the disease evolves and impacts the Gastrointestinal Tract (GIT), the window for effective treatment
response often becomes narrower for many patients. Recent advancements in medical science have
spurred improvements in drug delivery, primarily through the development of enhanced oral formulations
or the exploration of alternative administration routes, such as intestinal infusion, transcutaneous
delivery, and inhaled levodopa. Among the recent oral formulation breakthroughs is IPX066,
a novel formulation combining immediate and extended-release Carbidopa-Levodopa (CD/LD). Another
notable example is levodopa-carbidopa intestinal gel, an authorized treatment involving the
direct infusion of LD/CD suspension into the brain. Concurrent investigations are assessing the effectiveness
of the 'accordion pill' (AP09004), an Extended-release (ER) LD/CD mixture designed to
retain within the GIT for an extended period. Additionally, other formulations in various stages of
clinical trials include ND0612, a proprietary liquid formulation intended for the purpose of subcutaneous
delivery using a compact patch-pump apparatus, and CVT-301, a levodopa aerosol solution
distinguished by its prompt initiation of therapeutic effects. However, several other promising formulations,
such as DM-1992 and XP21279, have been terminated. This study aimed to thoroughly
examine the pharmacokinetics, clinical effectiveness, and possible adverse reactions linked to innovative
medication formulations that are now accessible or being developed for treating PD.
Reducing Stoichiometric Excess of Base to Catalytic Amount: Revisiting Staudinger Reaction for -lactam Synthesis
Authors: Yadav Sonu , Ray Devalina , Banik Bimal Krishna
Published: October 2024

Background:

-lactams have been primarily utilized as a leading class of effective antibiotics.
They have been found to show activity against various diseases, prompting the scientific
community to prioritise innovative protocols for their synthesis. The general and well-known synthetic
strategy involves the classical Staudinger reaction exhibiting [2+2] cycloaddition reaction.
However, the protocol utilizes stoichiometric excess of base for efficient product formation.

Objective:

A smarter and more acceptable approach for the synthesis of -lactams would be to
reduce the excess base to a catalytic amount, furnishing a catalytic version of the Staudinger reaction.
The modified version can eliminate the hazards arising out of excess use of the base, ultimately
promoting the environmentally benign approach.

Methods:

With this hypothesis, a base-catalyzed approach in dimethyl formamide (DMF) towards
the synthesis of -lactam via Staudinger reaction has been endorsed under moderate reaction conditions.

Results:

The scope of the substrates was explored with both electron-withdrawing and electronreleasing
substitutions in the formation of -lactam. The reduction of the base amount from stoichiometric
to catalytic amount was justified by the involvement of DMF in generating the basic
condition for the reaction.

Conclusion:

It was hypothesized that the decomposition of DMF under the base-catalysed reaction
condition can generate dimethylamine, which produces the required basic environment.

conclusion:

A base-catalysed approach in dimethyl formamide (DMF) towards the synthesis of β-lactam via Staudinger reaction has been endorsed under moderate reaction conditions. The substrates scope was explored with both electron withdrawing and electron releasing substitutions in the formation of β-lactam. The reduction of base amount from stoichiometric to catalytic was justified by the involvement of DMF in generating the basic condition for the reaction. It was hypothesized that the decomposition of DMF under the base catalysed reaction condition can generate dimethylamine which produces the required basic environment.
Current Progress in Visible Light-induced Synthesis and Functionalization of N- and S-Heterocycles: A Sustainable Perspective
Authors: Saha Debasree , Ranu Brindaban C.
Published: October 2024

Heterocycles are of much importance as the majority of the existing drugs contain one or
more heterocyclic units in their structures. Among all the heterocycles, nitrogen, and sulphurcontaining
ones occupy major space, and they have special properties which make them suitable for
the textile, cosmetic, and paint industries other than pharmaceutical. Recently, visible light has
emerged as a powerful tool for performing various reactions at ambient temperatures and mild
conditions and thus it has been used for the key step in the synthesis of many molecules. In addition,
visible light assisted methods are usually cost and time effective. Thus, this review highlighted the
recent developments in visible light induced methods for the synthesis of some selected biologically
active N- and S- containing heterocycles such as benzothiazoles, indoles and triazoles and their
functionalization. The advantages, green aspects and limitations of these methods have also been
discussed.
Recent Advancements of Graphene and Some Selected Graphene-Based Electrode Materials for Lithium-Ion Battery
Authors: Fayesa Tilahun Yai
Published: October 2024

Graphene is a two-dimensional monolayer of carbon atoms arranged in a hexagonal lattice
consisting of sp2 hybridized conjugated carbon atoms and serves as a promising electrode material
for lithium-ion batteries (LIBs) owing to its superior properties, including a high specific surface
area (2630 m2g-1), a high theoretical capacity (744 mAhg-1), excellent electrical conductivity,
and a wide electrochemical potential window. Despite having these superior properties, the restacking
as well as the van der Waals forces of attraction among the graphene layers and the long
path for Li-ion diffusion are factors that reduce the specific surface area and active site for Li-ion
storage, which in turn influence the electrochemical performance of LIBs. The functionalization
of graphene to porous graphene, graphene quantum dots, and graphene oxides, as well as the integration
of graphene with other foreign materials such as transitional metal oxides, various heteroatoms
(boron, nitrogen, sulfur, etc.), and covalent organic frameworks (COF), are the two main
strategies that have been widely applied to improve the properties of graphene for Li-ion battery
applications. In this review, recent works regarding the performance of graphene and graphenebased
electrode materials for LIBs applications were reviewed and presented in detail. Moreover,
various graphene fabrication techniques in terms of quality and quantity of graphene produced as
well as the future overview of graphene and some selected graphene-based materials for LIBs applications
have been assessed and summarized.
Review of Lipid Nanoparticles for Breast Cancer Management: Targeting Strategies and Clinical Perspective
Authors: Almurisi Samah Hamed , En Goo Wei , Hafiq Muhamad Zakwan , Sheng Leong Khai , Sri Prasanthi , Mazlan Nadiatul Azra Binti Ahmad , Bhatnagar Payal , Madheswaran Thiagarajan
Published: October 2024

Chemotherapy, a conventional breast cancer treatment, has limitations due to its nonspecific
mechanisms and undesirable side effects. Lipid-based nanoparticles (LNPs) have
emerged as a versatile and superior platform for targeted breast cancer treatment, offering several
distinct advantages over traditional therapies. This class of nanocarriers, which includes solid lipid
nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and liposomes, enhances the bioavailability
and stability of therapeutic agents while minimizing systemic toxicity. LNPs can be engineered
to precisely target breast cancer cells by exploiting tumor-specific markers, enabling selective
delivery of chemotherapeutic agents and reducing off-target effects. SLNs provide controlled
drug release and improved drug retention within the tumor, while NLCs offer higher drug-loading
capacities and better stability. Liposomes, with their flexible design, allow for the encapsulation
of both hydrophilic and hydrophobic drugs and can be modified for active targeting through surface
functionalization. These lipid-based carriers also address the challenges of multi-drug resistance
(MDR) by enhancing intracellular drug concentration and overcoming efflux mechanisms.
In this review, we focus on lipid-based nanoparticles- a subtype of nanoparticles, and their potential
advantages as drug delivery systems for breast cancer treatment. Results revealed that lipidbased
nanoparticles have shown potential in breast cancer management, these include improved
drug efficacy, enhanced ability to overcome cancer therapy resistance, and effective drug carrier
for co-loaded drugs.
De Lisboa a São Paulo: manuais cêntricos para uma língua intercultural
Authors: João Pires Manuel Duarte
Published: October 2024

A língua portuguesa é falada por milhões de pessoas que a utilizam e disseminam por todo o mundo. O ensino de Português Língua Estrangeira (PLE) deve promover uma cidadania intercultural que envolva conhecer, valorizar e respeitar a sua diversidade, reconhecendo que a língua é um veículo de diversas expressões culturais e identitárias. Este estudo desenvolve alguns pressupostos sobre o ensino de português para a interacção cultural iniciados no âmbito do trabalho realizado na tese de doutoramento (Pires, 2022b). O principal objetivo do presente artigo é analisar as perspetivas ou referências geográficas, sociais e interculturais presentes em quatro manuais para o ensino-aprendizagem de PLE, nomeadamente, Português XXI e Aprender Português, de Portugal, e, Falar... Ler... Escrever... Português e Muito Prazer, do Brasil. A meotodologia baseia-se numa pesquisa documental dos materiais sob uma abordagem analítica ou científica (Gil, 2008). Os resultados indicam que estes manuais não exprimem a diversidade e heterogeneidade da língua portuguesa. Nos manuais portugueses e brasileiros analisados, Lisboa e São Paulo, respetivamente, constituem referências recorrentes, cêntricas e hegemónicas em termos geográficos, sociais e culturais.
Choro N. 1, de Quincas Laranjeiras: manuscrito e critérios para uma nova edição
Authors: Amorim Humberto
Published: October 2024

Ancorado nos pressupostos teóricos de Figueiredo (2016) e coadunado com os esforços de resgatar o repertório pioneiro da guitarra no Brasil (Ávila et al., 2020; Habib, 2013, Lima 2023; Prando, 2022, 2023; Taborda, 2021), o artigo apresenta um manuscrito até então inédito do Choros N. 1, atribuído a um dos personagens antigos mais decisivos da guitarra carioca, Joaquim Francisco dos Santos, o Quincas Laranjeiras (1873–1935). O objetivo, de forma específica, é oferecer subsídios para uma edição moderna que colabore para a difusão da obra e, de forma geral, jogar luz tanto sobre a produção de Quincas recentemente redescoberta quanto sobre o significativo repertório do período que ainda precisa ser explorado.
Exploring STEM Learning Information Sources for Rural Children and Caregivers
Authors: Kim Soo Hyeon , Choi Gi Woong , Kang Ju Hui
Published: October 2024

An understanding of how people seek and use information is foundational to the development of public library services. This poster explores what information sources rural caregivers seek out to support children’s STEM learning in their everyday life and at public libraries, and the level of trust towards the information sources. We conducted a case study of 20 rural caregivers with children (5-11 years) from five different States. Online surveys were distributed, asking participants to rate the level of trustworthiness for each information source they seek out when they support children’s STEM learning. The survey also asked participants to share how they use the public library for STEM learning by sharing specific anecdotes and describe the reasons for using or not using the library for STEM learning. Preliminary findings provide insights into the relationship between the most frequently used and the least trusted information sources that rural caregivers seek out to support their children’s STEM learning. The findings further guide LIS researchers and practitioners in designing public library services and programming for rural communities with valid and reliable sources of information for STEM learning.
CYBERSECURITY IN IIOT AND IOMT NETWORKS USING MACHINE LEARNING ALGORITHMS - A SURVEY
Authors:   I.K. Gujral Punjab Technical University, India, Arora Pallavi , Kaur Baljeet ,   Guru Nanak Dev Engineering College, India, Teixeira Marcio Andrey ,   Federal Institute of Education, Science, and Technology of Sao Paulo, Brazil
Published: October 2024

Rapid advancements in micro-computing, mini-hardware manufacturing, and machine-to-machine (M2M) communications have allowed for innovative Internet of Things (IoT) solutions to redefine numerous networking applications. With the emergence of IoT branches such as the Internet of Medical Things (IoMT) and the Industrial Internet of Things (IIoT), healthcare and industrial systems have been changed by IoT. This paper presents an overview of the technologies that are being used to secure IoMT as well as IIoT frameworks seen within the research articles.
Testing 3 Modalities (Voice Assistant, Chatbot, and Mobile App) to Assist Older African American and Black Adults in Seeking Information on Alzheimer Disease and Related Dementias: Wizard of Oz Usability Study
Authors: Bosco Cristina , Shojaei Fereshtehossadat , Theisz Alec Andrew , Osorio Torres John , Cureton Bianca , Himes Anna K , Jessup Nenette M , Barnes Priscilla A , Lu Yvonne , Hendrie Hugh C , Hill Carl V , Shih Patrick C
Published: October 2024

Background

Older African American and Black adults are twice as likely to develop Alzheimer disease and related dementias (ADRD) and have the lowest level of ADRD health literacy compared to any other ethnic group in the United States. Low health literacy concerning ADRD negatively impacts African American and Black people in accessing adequate health care.

Objective

This study explored how 3 technological modalities—voice assistants, chatbots, and mobile apps—can assist older African American and Black adults in accessing ADRD information to improve ADRD health literacy. By testing each modality independently, the focus could be kept on understanding the unique needs and challenges of this population concerning the use of each modality when accessing ADRD-related information.

Methods

Using the Wizard of Oz usability testing method, we assessed the 3 modalities with a sample of 15 older African American and Black adults aged >55 years. The 15 participants were asked to interact with the 3 modalities to search for information on local events happening in their geographical area and search for ADRD-related health information.

Results

Our findings revealed that, across the 3 modalities, the content should avoid convoluted and complex language and give the possibility to save, store, and share it to be fully accessible by this population. In addition, content should come from credible sources, including information tailored to the participants’ cultural values, as it has to be culturally relevant for African American and Black communities. Finally, the interaction with the tool must be time efficient, and it should be adapted to the user’s needs to foster a sense of control and representation.

Conclusions

We conclude that, when designing ADRD-related interventions for African American and Black older adults, it proves to be crucial to tailor the content provided by the technology to the community’s values and construct an interaction with the technology that is built on African American and Black communities’ needs and demands.
Enhancing Mixed Reality Simulation Training Technology with Real-Time Performance Visualization: Mixed Methods Study with Medical First Responders (Preprint)
Authors: Zechner Olivia , Schrom-Feiertag Helmut , Wespi Rafael , Pretolesi Daniele , Nguyen Quynh , Tscheligi Manfred
Published: October 2024

BACKGROUND

Mixed Reality (MR) simulation training is emerging in paramedical education for practicing stress-intensive scenarios like mass casualty incidents in a safe and controlled environment. Current training platforms, however, lack real-time stress and human performance monitoring tools.

OBJECTIVE

The study aims to enhance mixed reality training for medical first responders through real-time evaluation of performance and stress levels, leveraging bio-signal monitoring and advanced analytics to allow instructors to tailor feedback and maintain optimal challenge and safety levels.

METHODS

The study includes a structured, multi-phase approach including initial requirement gathering (structured interviews and co-creation workshops), an online design survey, iterative prototype development and a field trial (including training observations and interviews). Data was collected from five end-user consortium members across Europe. Quantitative data from checklists were analyzed using frequencies and percentages to understand feature usage and event occurrences. Qualitative data from semi-structured interviews and co-creation workshops were transcribed, coded and subjected to thematic analysis to identify patterns and insights into the usability and effectiveness of the enhanced features on the MR training.

RESULTS

The study identified a wide range of requirements Medical First Responders (MFRs) have towards a MR training system that go beyond currently available solutions. A total of 80 performance metrics were initially identified and refined to a set of 54, which were categorized into KPI groups such as scene safety, triage performance and communication. Requirements for smart wearables to monitor stress levels are provided and highlight the importance of a user-centered design process to provide users with effective tools that fit their needs. Stress visualization preferences are described in form of a dashboard as well as in virtual environments surrounding the avatar. Using an iterative design process and user feedback, a training system was developed, integrating real-time performance tracking and stress monitoring. The field trial provided insights into practical use of these features during a real training exercise, showed interaction preferences between trainer and trainees and highlighted further improvement opportunities.

CONCLUSIONS

This research enhances MR training for paramedics by integrating real-time performance metrics and stress indicators, based on a human-centered design approach that aligns with end-user needs, thereby setting a foundation for developing more effective and immersive training solutions for high-stress professions.

CLINICALTRIAL