bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of the bitter taste genes TAS2R38 and CA6 and breast cancer risk; a case-control study of Polish women in Poland and Polish immigrants in USA
Authors: Łukasiewicz-Śmietańska Dorota , Godlewski Dariusz , Nowakowska Elżbieta , Szpak Andrzej , Chabros Elżbieta , Juszczyk Grzegorz , Charzewska Jadwiga , Rybaczyk-Pathak Dorothy
Published: April 2024

It is known that the perception of bitterness is mediated by type 2 bitter taste receptors (TAS2Rs). However, recent reports have suggested that the carbonic anhydrase 6 (CA6) gene may also influence bitterness sensing. Genetic variants in these genes could influence dietary intake of brassica vegetables, whose increased consumption has been observed in the literature, though inconsistently, to decrease breast cancer (BC) risk. We hypothesized that the estimated odds ratios (ORs) for the association between BC and taster diplotype (PAV/PAV) and/or genotype A/A, will be in the direction of increased BC risk, potentially due to reduced consumption of brassica vegetables. Using a case-control study of BC in Polish women in Poland (210 cases and 262 controls) and Polish immigrant women to USA (78 cases and 170 controls) we evaluated the association of the taster diplotypes in TAS2R38 gene and genotypes in the CA6 gene and BC risk in these two populations individually and jointly. No significant increase in risk was observed for the TAS2R38 PAV/PAV diplotype (tasters) in each population individually or in the joint population. For the CA6 gene, in the joint population, we observed an increased BC risk for the combined G/A and G/G genotypes (non-tasters) vs A/A (tasters), OR = 1.41 (95% CI 1.04–1.90, p = 0.026) which after adjustment for False Discovery Rate (FDR), was not significant at p≤0.05 level. However, for the joint population and for the combined genotype of the two genes AVI/AVI+G* (non-tasters) vs. PAV/*+A/A (tasters), we observed a significant increase in BC risk, OR = 1.77 (95%CI 1.47–2.74, p = 0.01), for the non-tasters, which remained significant after FDR adjustment. In conclusion for the joint population and the joint effect for the two bitter sensing genes, we observed an increase in BC risk for the bitterness non-tasters, association which is in the opposite direction to our original hypothesis.
Host influence on the eukaryotic virome of sympatric mosquitoes and abundance of diverse viruses with a broad host range
Authors: Morel Côme , Gil Patricia , Exbrayat Antoni , Loire Etienne , Charriat Florian , Prepoint Baptiste , Condachou Celine , Gimonneau Geoffrey , Fall Assane Gueye , Biteye Biram , Seck Momar Talla , Eloit Marc , Gutierrez Serafin
Published: April 2024

Mosquitoes harbor a large diversity of eukaryotic viruses. Those viromes probably influence mosquito physiology and the transmission of human pathogens. Nevertheless, their ecology remains largely unstudied. Here, we address two key questions in virome ecology. First, we assessed the influence of mosquito species on virome taxonomic diversity and relative abundance. Contrary to most previous studies, the potential effect of the habitat was explicitly included. Thousands of individuals of Culex poicilipes and Culex tritaeniorhynchus, two vectors of viral diseases, were concomitantly sampled in three habitats over two years. A total of 95 viral taxa from 25 families were identified with meta-transcriptomics, with 75% of taxa shared by both mosquitoes. Viromes significantly differed by mosquito species but not by habitat. Differences were largely due to changes in relative abundance of shared taxa. Then, we studied the diversity of viruses with a broad host range. We searched for viral taxa shared by the two Culex species and Aedes vexans, another disease vector, present in one of the habitats. Twenty-six out of the 163 viral taxa were found in the three mosquitoes. These taxa encompassed 14 families. A database analysis supported broad host ranges for many of those viruses, as well as a widespread geographical distribution. Thus, the viromes of mosquitoes from the same genera mainly differed in the relative abundance of shared taxa, whereas differences in viral diversity dominated between mosquito genera. Whether this new model of virome diversity and structure applies to other mosquito communities remains to be determined.
Validity and reliability of the Thai version of the ASCRS SPEED II preoperative OSD questionnaire in Thai cataract surgery candidates
Authors: Lekhanont Kaevalin , Ariyanonthacha Paphada , Wongrathanandha Chathaya , Phimpho Prae , Cheewaruangroj Nontawat
Published: April 2024

Objectives

To develop a Thai version of the American Society of Cataract and Refractive Surgery (ASCRS)-modified Standard Patient Evaluation of Eye Dryness (SPEED) II© preoperative ocular surface disease (OSD) questionnaire (ASCRS SPEED II-Thai) and evaluate its validity and reliability in Thai cataract surgery candidates.

Methods

The original English version of the questionnaire was translated and adapted cross-culturally to Thai language. The ASCRS SPEED II-Thai was evaluated for content validity, internal consistency, and test-retest reliability. Five experts in the ocular surface field critically reviewed the ASCRS SPEED II-Thai to measure the content validity indexes (CVI). A total of 105 cataract surgery candidates were recruited from an ophthalmology clinic to complete the questionnaire. Cronbach’s alpha and intraclass correlation coefficient (ICC) were calculated to assess internal consistency and test–retest reliability, respectively.

Results

During the translation and cross-cultural adaptation processes, only two minor modifications were made to the original version for clarification without changing their meaning. All items in the ASCRS SPEED II-Thai had an item-level CVI of 1.00, representing complete agreement among content experts. The scale-level CVI was 1.00, indicating excellent content validity of the questionnaire. The participants found no difficulty in understanding each question in the pilot test. Cronbach’s alpha for the ASCRS SPEED II-Thai was 0.82, indicating good internal consistency. The test-retest reliability was good to excellent, with ICC values ranging from 0.83 to 1.00 (P < 0.001).

Conclusions

The ASCRS SPEED II-Thai is a valid clinical tool with adequate reliability for preoperative OSD screening among Thai cataract surgery candidates.
Trend change analysis in the assessment of body balance during posture adjustment in reaction to anterior-posterior ground perturbation
Authors: Wodarski Piotr , Chmura Marta , Szlęzak Michał , Bajor Grzegorz , Gzik Marek , Jurkojć Jacek
Published: April 2024

Postural adjustments (PA) occur to counteract predictable perturbations and can be impaired as a result of musculoskeletal and neurological dysfunctions. The most common way to detect PA is through electromyography measurements or center of pressure (COP) position measurements, where analysis in time domain and frequency domain are the most common. Aim of the research was to determine whether a new method of analyzing stabilographic measurements—the COP trend change analysis (TCI) of temporary posture corrections- can expand understanding of changes in balance strategy connected with PA. The study group involved 38 individuals (27women, 11men) aged 23±2.6 years. Measurements were performed using a stabilographic platform placed on a perturbation platform. The tests involved three measurements with forward and backward momentary movements of the platform. Participants were tested in three conditions–knowing the nature, time and direction of perturbation (Tr3), knowing only the nature of perturbation (Tr2) and without any information about the perturbation (Tr1). Statistically significant differences were revealed in the last second of Tr3 for the mean velocity of COP (p<0.05) and for two TCI parameters–TCI_dV (p<0.05) and TCI_dS (p<0.01). The increase in TCI_dV was related to the increase in the mean distance between trend changes (TCI_dS) and constant value of the mean time between trend changes (TCI_dT). The increase of the mean value of TCI_dS was the result of smaller number of posture corrections with the distance 0–2 mm and lager number with the distance 4–6 mm. Obtained results proved that the TCI analysis is a method enabling an extended analysis of PA, indicating the nature of changes occurring in posture corrections–longer momentary jumps of COP–related to a change in the strategy of maintaining balance before a known disorder, which has not been analyzed in this type of research so far.
Diagnostic accuracy of the Enferplex Bovine TB antibody test using individual milk samples from cattle
Authors: O’Brien Amanda , Hayton Alastair , Cutler Keith , Adler Andy , Shaw Darren J. , Clarke John , Watt Neil , Harkiss Gordon D.
Published: April 2024

Bovine tuberculosis is usually diagnosed using tuberculin skin tests or at post-mortem. Recently, we have developed a serological test for bovine tuberculosis in cattle which shows a high degree of accuracy using serum samples. Here, we have assessed the performance of the test using individual bovine milk samples. The diagnostic specificity estimate using the high sensitivity setting of the test was 99.7% (95% CI: 99.2–99.9). This estimate was not altered significantly by tuberculin boosting. The relative sensitivity estimates of the test using the high sensitivity setting in milk samples from comparative skin test positive animals was 90.8% (95% CI: 87.1–93.6) with boosting. In animals with lesions, the relative sensitivity was 96.0% (95% CI: 89.6–98.7). Analysis of paired serum and milk samples from skin test positive animals showed correlation coefficients ranging from 0.756–0.955 for individual antigens used in the test. Kappa analysis indicated almost perfect agreement between serum and milk results, while McNemar marginal homogeneity analysis showed no statistically significant differences between the two media. The positive and negative likelihood ratio were 347.8 (95% CI: 112.3–1077.5) and 0.092 (95% CI: 0.07–0.13) respectively for boosted samples from skin test positive animals. The results show that the test has high sensitivity and specificity in individual milk samples and thus milk samples could be used for the diagnosis of bovine tuberculosis.
Nurturing an organizational context that supports team-based primary mental health care: A grounded theory study
Authors: Ashcroft Rachelle , Menear Matthew , Dahrouge Simone , Silveira Jose , Emode Monica , Booton Jocelyn , Bahniwal Ravninder , Sheffield Peter , McKenzie Kwame
Published: April 2024

Background

The expansion of the Patient-Centred Medical Home model presents a valuable opportunity to enhance the integration of team-based mental health services in primary care settings, thereby meeting the growing demand for such services. Understanding the organizational context of a Patient-Centred Medical Home is crucial for identifying the facilitators and barriers to integrating mental health care within primary care. The main objective of this paper is to present the findings related to the following research question: "What organizational features shape Family Health Teams’ capacity to provide mental health services for depression and anxiety across Ontario, Canada?"

Methods

Adopting a constructivist grounded theory approach, we conducted interviews with various mental health care providers, and administrators within Ontario’s Family Health Teams, in addition to engaging provincial policy informants and community stakeholders. Data analysis involved a team-based approach, including code comparison and labelling, with a dedicated data analysis subcommittee convening monthly to explore coded concepts influencing contextual factors.

Results

From the 96 interviews conducted, involving 82 participants, key insights emerged on the organizational contextual features considered vital in facilitating team-based mental health care in primary care settings. Five prominent themes were identified: i) mental health explicit in the organizational vision, ii) leadership driving mental health care, iii) developing a mature and stable team, iv) adequate physical space that facilitates team interaction, and v) electronic medical records to facilitate team communication.

Conclusions

This study underscores the often-neglected organizational elements that influence primary care teams’ capacity to deliver quality mental health care services. It highlights the significance of strong leadership complemented by effective communication and collaboration within teams to enhance their ability to provide mental health care. Strengthening relationships within primary care teams lies at the core of effective healthcare delivery and should be leveraged to improve the integration of mental health care.
Does small talk with a medical provider affect ChatGPT’s medical counsel? Performance of ChatGPT on USMLE with and without distractions
Authors: Safrai Myriam , Azaria Amos
Published: April 2024

Efforts are being made to improve the time effectiveness of healthcare providers. Artificial intelligence tools can help transcript and summarize physician-patient encounters and produce medical notes and medical recommendations. However, in addition to medical information, discussion between healthcare and patients includes small talk and other information irrelevant to medical concerns. As Large Language Models (LLMs) are predictive models building their response based on the words in the prompts, there is a risk that small talk and irrelevant information may alter the response and the suggestion given. Therefore, this study aims to investigate the impact of medical data mixed with small talk on the accuracy of medical advice provided by ChatGPT. USMLE step 3 questions were used as a model for relevant medical data. We use both multiple-choice and open-ended questions. First, we gathered small talk sentences from human participants using the Mechanical Turk platform. Second, both sets of USLME questions were arranged in a pattern where each sentence from the original questions was followed by a small talk sentence. ChatGPT 3.5 and 4 were asked to answer both sets of questions with and without the small talk sentences. Finally, a board-certified physician analyzed the answers by ChatGPT and compared them to the formal correct answer. The analysis results demonstrate that the ability of ChatGPT-3.5 to answer correctly was impaired when small talk was added to medical data (66.8% vs. 56.6%; p = 0.025). Specifically, for multiple-choice questions (72.1% vs. 68.9%; p = 0.67) and for the open questions (61.5% vs. 44.3%; p = 0.01), respectively. In contrast, small talk phrases did not impair ChatGPT-4 ability in both types of questions (83.6% and 66.2%, respectively). According to these results, ChatGPT-4 seems more accurate than the earlier 3.5 version, and it appears that small talk does not impair its capability to provide medical recommendations. Our results are an important first step in understanding the potential and limitations of utilizing ChatGPT and other LLMs for physician-patient interactions, which include casual conversations.
Identification and classification of surface defects for digital twin models of the workpiece
Authors: Qu Ligang , Huang Xuesong , Zhang Danya , Chen Zeng
Published: April 2024

Workpiece surface defect detection is an indispensable part of intelligent production. The surface information obtained by traditional 2D image detection has some limitations due to the influence of environmental light factors and part complexity. However, the digital twin model has the characteristics of high fidelity and scalability, and the digital twin surface can be obtained by a device with a scanning accuracy of 0.02mm to achieve the representation of the real surface of the workpiece. The surface defect detection system for digital twin models is proposed based on the improved YOLOv5 model in this paper. Firstly, the digital twin model of the workpiece is reconstructed by the point cloud data obtained by the scanning device, and the surface features with defects are captured. Subsequently, the training dataset is calibrated based on the defect surface, where the defect types include Inclusion, Perforation, pitting surface and Rolled-in scale. Finally, the improved YOLOv5 model with CBAM mechanism and BiFPN module was used to identify the surface defects of the digital twin model and compare it with the original YOLOv5 model and other common models. The results show that the improved YOLOv5 model can realize the identification and classification of surface defects. Compared with the original YOLOv5 model, the mAP value of the improved YOLOv5 model has increased by 0.2%, and the model has high precision. On the basis of the same data set, the improved YOLOv5 model has higher recognition accuracy than other models, improving 11.7%, 3.4%, 6.2%, 33.5%, respectively. As a result, this study provides a practical and systematic detection method for digital twin model surface during the intelligent production process, and realizes the rapid screening of the workpiece with defects.
Effect of adding Schroth physiotherapeutic scoliosis specific exercises to standard care in adolescents with idiopathic scoliosis on posture assessed using surface topography: A secondary analysis of a Randomized Controlled Trial (RCT)
Authors: Mohamed Nada , Acharya Vivechana , Schreiber Sanja , Parent Eric C. , Westover Lindsey
Published: April 2024

Background

Adolescent idiopathic scoliosis (AIS) is a three-dimensional structural asymmetry of the spine and trunk affecting 2–4% of adolescents. Standard treatment is observation, bracing, and surgery for small, moderate, and large curves, respectively. Schroth exercises aim to correct posture and reduce curve progression.

Purpose

This study aimed to determine the effect of Schroth exercises added to the standard care compared to standard care alone on torso asymmetry in AIS.

Methods

In a randomized controlled trial (NCT01610908), 124 participants with AIS (age: 10–18, Cobb: 10°-45°, Risser: ≤3) were randomly assigned to the control (Standard care only) or Schroth (Standard care + Schroth treatment) group. Schroth treatment consisted of 1-hour weekly supervised sessions and 30–45 minutes of daily home exercises for six months. The control group received Schroth exercises in the last six months of the 1-year monitoring period. Markerless 3D surface topography assessed torso asymmetry measured by maximum deviation (MaxDev) and root mean square (RMS). Intention to treat linear mixed effects model analysis was compared to the per protocol analysis.

Results

In the intention to treat analysis, the Schroth group (n = 63) had significantly larger decreased RMS (-1.2 mm, 95%CI [-1.5,-0.9]mm, p = 0.012) and MaxDev (-1.9mm, 95%CI [-2.4,-1.5]mm, p = 0.025) measurements compared to controls (n = 57) after six months of intervention. In the per protocol analysis (Schroth n = 39, control n = 36), the Schroth group also had a significantly larger decrease compared to the control in both the RMS (-1.0mm, 95%CI [-1.9, -0.2]mm, p = 0.013) and MaxDev measurements (-2.0mm, 95%CI [-3.3,-0.5]mm, p = 0.037). For the control group, both the intention to treat and per protocol analysis showed no difference in RMS and MaxDev in the last six months of Schroth intervention (p>0.5).

Conclusion

Schroth Exercise treatment added to standard care (observation or bracing) reduced asymmetry measurements in AIS. As expected, a greater effect was observed for participants who followed the prescribed exercise treatment per protocol.
Zhilong Huoxue Tongyu capsule improves myocardial ischemia/reperfusion injury via the PI3K/AKT/Nrf2 axis
Authors: Zhao Xiaoping , Yang Fang , Wu Hao , Fan Zhongcai , Wei Gang , Zou Yuan , Xue Jinyi , Liu Mengnan , Chen Gong
Published: April 2024

Introduction

Zhilong Huoxue Tongyu Capsule (ZL) is a Chinese medicine used for the treatment of cardio-cerebral diseases. However, the pharmacological mechanisms underlying its regulation of myocardial ischemia/reperfusion injury (MI/RI) remain unclear.

Purpose

This study aims to investigate the effects and mechanisms of ZL on MI/RI in mice.

Materials and methods

C57BL/6J mice were randomly assigned to four groups: Sham group, I/R group, ZL group, and ZLY group. The MI/RI mouse model was established by ligation of the left anterior descending coronary artery for 30 minutes, followed by reperfusion for 120 minutes to restore blood perfusion. Cardiac function was evaluated using cardiac ultrasound. Histopathological changes and myocardial infarction area were assessed using Hematoxylin and eosin (H&E) staining and triphenyltetrazolium chloride (TTC) staining. The changes in oxidative stress- and ferroptosis-related markers were detected. RT-qPCR, Western blot, and ELISA were conducted to further explore the mechanism of ZL in improving MI/RI.

Results

Our findings demonstrated that ZL exerted a protective effect against MI/RI by inhibiting ferroptosis, evidenced by the upregulation of antioxidant enzymes such as GSH and GPX4, coupled with the downregulation of ACSL4, a pro-ferroptosis factor. Furthermore, ZL positively impacted the PI3K/AKT/Nrf2 pathway by promoting ATPase activities and enhancing the relative protein expression of its components. Notably, the administration of a PI3K/AKT inhibitor reversed the antioxidant and anti-ferroptosis effects of ZL to some extent, suggesting a potential role for this pathway in mediating ZL’s protective effects.

Conclusions

ZL protects against MI/RI-induced ferroptosis by modulating the PI3K/AKT signaling pathway, leading to increased Nrf2 expression and activation of the HO-1/GPX4 pathway. These findings shed light on the potential therapeutic mechanisms of ZL in the context of cardiovascular diseases.
Individual and systemic variables associated with prolonged grief and other emotional distress in bereaved children
Authors: Boelen Paul A. , Spuij Mariken
Published: April 2024

Most children confronted with the death of a loved one do not experience persisting psychological problems. However, for some, acute grief reactions develop into prolonged grief disorder (PGD) and other mental health problems. Research findings suggest that bereavement outcomes in children are associated with negative cognitions and avoidant coping and with different parenting behaviours. However, knowledge about factors influencing grief in children is still limited and few studies have examined the relative impact of psychological (individual-level) variables and systemic (family-level) variables in affecting their responses to loss. The aim of the current study was to examine the association of different bereavement outcomes in 8–18 year old children (including levels of self-rated PGD, depression, and posttraumatic stress (PTS)) with sociodemographic variables, individual-level variables (including negative cognitions and anxious and depressive avoidance), and family-level variables (including the severity of caregiver’s PGD, depression, and anxiety, and indices of parenting behaviours, rated both by children and by their caregivers). Questionnaire data were used from 159 children plus one of their caregivers, gathered as part of the pre-treatment assessment in a randomized controlled trial. Results showed that most of the children’s bereavement outcomes, including PGD severity and PTS severity, were associated with indices of negative cognitions and avoidance behaviours. Caregiver’s depression and anxiety showed a very small, yet significant, association with two children’s outcomes. Caregiver-rated reasoning/induction (one index of parenting behaviours) showed a small association with children’s PTS-related functional impairment. Exploratory analyses indicated that the linkage between parenting behaviour and children’s outcomes may be moderated by whether the behaviour comes from father or mother. This is one of the first studies examining how individual cognitive behavioural variables plus the mental health of caregivers and indices of parenting may affect PGD and other outcomes in bereaved children. The findings provide tentative indications that individual and family-level variables influence these outcomes, albeit that more research is urgently needed.
The barrier-protective effect of β-eudesmol against type 2-inflammatory cytokine-induced tight junction disassembly in airway epithelial cells
Authors: Tharabenjasin Phuntila , Moonwiriyakit Aekkacha , Sontikun Jenjira , Timpratueang Kanokphorn , Kuno Suhaibee , Aiebchun Thitinan , Jongkon Nathjanan , Mongkolrob Rungrawee , Pabalan Noel , Choowongkomon Kiattawee , Muanprasat Chatchai
Published: April 2024

Allergic inflammation, which is the pathogenesis of allergic rhinitis and asthma, is associated with disruption of the airway epithelial barrier due to the effects of type 2 inflammatory cytokines, i.e. interleukin-4 and interleukin-13 (IL-4/13). The anti-allergic inflammatory effect of β-eudesmol (BE) on the tight junction (TJ) of the airway epithelium has not previously been reported. Herein, the barrier protective effect of BE was determined by measurement of transepithelial electrical resistance and by paracellular permeability assay in an IL-4/13-treated 16HBE14o- monolayer. Pre-treatment of BE concentration- and time- dependently inhibited IL-4/13-induced TJ barrier disruption, with the most significant effect observed at 20 μM. Cytotoxicity analyses showed that BE, either alone or in combination with IL-4/13, had no effect on cell viability. Western blot and immunofluorescence analyses showed that BE inhibited IL-4/13-induced mislocalization of TJ components, including occludin and zonula occludens-1 (ZO-1), without affecting the expression of these two proteins. In addition, the mechanism of the TJ-protective effect of BE was mediated by inhibition of IL-4/13-induced STAT6 phosphorylation, in which BE might serve as an antagonist of cytokine receptors. In silico molecular docking analysis demonstrated that BE potentially interacted with the site I pocket of the type 2 IL-4 receptor, likely at Asn-126 and Tyr-127 amino acid residues. It can therefore be concluded that BE is able to prevent IL-4/13-induced TJ disassembly by interfering with cytokine-receptor interaction, leading to suppression of STAT6-induced mislocalization of occludin and ZO-1. BE is a promising candidate for a therapeutic intervention for inflammatory airway epithelial disorders driven by IL-4/13.
How to utilize natural regeneration of birch to establish mixed spruce-birch forests in Finland?
Authors:   Natural Resources Institute Finland (Luke), Natural resources, Latokartanonkaari 9, FI-00790 Helsinki, Finland, Männistö Lauri , Miina Jari , Huuskonen Saija
Published: April 2024

Mixed forests are known for their ability to provide a wide range of ecosystem services. Such forests have higher biodiversity compared to monocultures, are resilient against disturbances and may mitigate the effects of climate change. Despite well-known benefits, there is still little information on how these forests should be established and managed. The aim of this study was to describe the early growth dynamics of current boreal young mixed stands of planted Norway spruces (Picea abies (L.) Karst.) and naturally regenerated birches (Betula spp.). We collected data from 9 stands planted for spruce 8–14 years ago in Southern and Central Finland. Stem analysis was conducted to 144 spruces and to 144 birches to determine previous growth. We modelled the height and diameter development of individual trees in relation to tree age at stump height using non-linear mixed Chapman-Richards model. There were no significant differences between spruce and seed-origin birch in diameter growth at stump height, but the initial height increments of natural birches were larger than those of planted spruces. However, planted spruces were able to keep up with the height development of birches, if spruces received a head start over naturally regenerated seed-origin birch for two growing seasons. Thus, naturally regenerated birch admixture can be utilized to establish single-storied spruce-birch mixtures, and the admixture should be retained during the early cleaning of planted spruce stands.
1,2,3-Triazole Containing Hybrids as Potential Pharmacological Agents: A Review
Authors: Masood Mir Mohammad , Iqbal Arshid
Published: April 2024

1,2,3-Triazoles constitute a versatile class of nitrogen containing five-membered heterocycles, exhibiting wide range of pharmacological properties which include antibacterial, antifungal, anticancer, antimalarial, antidiabetic, anti-inflammatory, antihypertensive and antioxidant, among various others. Medicinal chemists have been interested in this aromatic ring as a framework since the inception of click chemistry as considered as the building block of contemporary organic chemistry. Extensive research into this framework’s linker characteristic has led to the synthesis and evaluation of numerous 1,2,3-triazole hybrids bearing a wide range of heterocyclic moieties as potential leads for various biological targets. This molecular hybridization has also added advantage of the improved pharmacological activity overcoming the problem of multiple drug resistance and reduced toxicity. This review summarizes the pharmacological activities of various 1,2,3-triazole containing hybrids and conjugates, covering articles published in past decade (2013 till date) and will be of great assistance to medicinal chemistry researchers in providing a useful direction for the future drug discovery.
A Catalytic Reduction of 4-Nitrophenol Utilizing Bimetallic CuO-Co3O4 Nanoparticles Synthesized via Wrightia tinctoria Extract: A Green Approach
Authors: Jeevarathinam M. , Halder Abhishikta , Manoj Archana , Asharani I.V.
Published: April 2024

In this investigation, copper oxide (CuO), cobalt oxide (Co3O4) and bimetallic copper oxide-cobalt oxide (CuO-Co3O4) nanoparticles were synthesized using an aqueous extract of Wrightia tinctoria leaves and characterized through UV-Vis, FT-IR, XRD, TEM and zeta potential analyses. The FT-IR analysis identified that specific phytoconstituents are responsible for the reduction and capping agents in nanoparticle synthesis. TEM analysis determined size and shape and zeta potential analysis assessed stability. The CuO and Co3O4 NPs, synthesized through an eco-friendly approach, were employed for 4-nitrophenol reduction with sodium borohydride. The reaction rate, was computed at 1 × 10-4 s-1, which indicated the pseudo-first-order kinetics. The synthesis of 4-aminophenol was also successfully acheived demonstrated that the excellent catalytic activity of CuO, Co3O4 and CuO-Co3O4 nanoparticles as catalysts.
Multicenter, Prospective Trial of Nonendoscopic Biomarker-Driven Detection of Barrett's Esophagus and Esophageal Adenocarcinoma
Authors: Moinova Helen R. , Verma Suman , Dumot John , Faulx Ashley , Iyer Prasad G. , Canto Marcia Irene , Wang Jean S. , Shaheen Nicholas J. , Thota Prashanthi N. , Aklog Lishan , Willis Joseph E. , Markowitz Sanford D. , Chak Amitabh
Published: April 2024

INTRODUCTION:

Preliminary data suggest that an encapsulated balloon (EsoCheck), coupled with a 2 methylated DNA biomarker panel (EsoGuard), detects Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) with high accuracy. The initial assay requires sample freezing upon collection. The purpose of this study was to assess a next-generation EsoCheck sampling device and EsoGuard assay in a much-enlarged multicenter study clinically enhanced by using a Clinical Laboratory Improvement Amendments of 1988-compliant assay and samples maintained at room temperature.

METHODS:

Cases with nondysplastic BE (NDBE), dysplastic BE (indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia), EAC, junctional adenocarcinoma, plus endoscopy controls without esophageal intestinal metaplasia, were prospectively enrolled. Medical assistants at 6 institutions delivered the encapsulated balloon per orally with inflation in the stomach. The inflated balloon sampled the distal 5 cm of the esophagus and then was deflated and retracted into the capsule, preventing sample contamination. EsoGuard bisulfite sequencing assayed levels of methylated vimentin and methylated cyclin A1.

RESULTS:

A total of 243 evaluable patients—88 cases (median age 68 years, 78% men, 92% White) and 155 controls (median age 57 years, 41% men, 88% White)—underwent adequate EsoCheck sampling. The mean procedural time was approximately 3 minutes. Cases included 31 with NDBE, 16 with indefinite for dysplasia/low-grade dysplasia, 23 with high-grade dysplasia, and 18 with EAC/junctional adenocarcinoma. Thirty-seven NDBE and dysplastic BE cases (53%) were short-segment BE (<3 cm). Overall sensitivity was 85% (95% confidence interval 0.78–0.93) and specificity was 85% (95% confidence interval 0.79–0.90). Sensitivity for NDBE was 84%. EsoCheck/EsoGuard detected 100% of cancers (n = 18).

DISCUSSION:

EsoCheck/EsoGuard demonstrated high sensitivity and specificity in detecting BE and BE-related neoplasia.
Holding a mirror up to Academic Development through the HELTASA (un)conferencing methodology
Authors: Williams Sandra , Adams Anthea , Geduld-Van Wyk Charlene , Muhuro Patricia
Published: April 2024

We, Academic Development (AD) practitioners, question whether AD's objective in South Africa (SA) as a 'liberatory educational and social movement' to enhance educational quality for all students, is effectively pursued. AD practitioners often work on the fringes of the academy, fighting for relevance and legitimacy within an increasingly performative and managerialist academic culture. Despite innovative AD initiatives AD work is criticised for being unresponsive, unreflexive, conformist, and lacking theoretical, scholarly, and critical engagement. We use critical pedagogical praxis, particularly the constructs of critique, reflexivity, power, and self-reflection, to interrogate the continuous tension between AD intention and practice. Through (un)conference methodology, this auto-ethnographic account of individual and collective engagements, using the "holding the mirror up" metaphor, critically questioned the tension and misalignments between the AD mandate and practices. Although in a SA higher education context, this research could be beneficial to HE contexts globally, given the ubiquity of AD work.
Headstall
Authors: Phillips Jolyn
Published: April 2024

My father is the healthiest I have ever seen him. He is brown again. His liver is healing. His eyes are glistening because they are happy to see me not because he is too intoxicated to talk. His beard is shaven, white stubble sitting quietly on his skin. His hair is shaven with a no.2 blade. He is spick ’n span. The last time he was sober he was attending my book launch with my mother (legally blind), aunt, uncle (who is blind now). My father was agitated in the bookshop and found every utterance and the fidgeting of my mother a disturbance to his church. My mother was the same. They argued like crumpled up paper. I hugged him sort of reluctantly since he always reeked of alcohol. It would sweat out of his pores. He was shaking and smoking, leaning against the bookshelf, completely out of place in his funeral best.
Dronedarone for the Treatment of Atrial Arrhythmias in Adults With Congenital Heart Disease
Authors: Agha Mahdi S. , Ermis Peter R. , Franklin Wayne J. , Parekh Dhaval R. , Opina Angeline D. , Kim Jeffrey J. , Miyake Christina Y. , Valdes Santiago O. , Lam Wilson W.
Published: April 2024

Background:

Atrial tachyarrhythmias are common and difficult to treat in adults with congenital heart disease. Dronedarone has proven effective in patients without congenital heart disease, but data are limited about its use in adults with congenital heart disease of moderate to great complexity.

Methods:

A single-center, retrospective chart review of 21 adults with congenital heart disease of moderate to great complexity who were treated with dronedarone for atrial tachyarrhythmias was performed.

Results:

The median (IQR) age at dronedarone initiation was 35 (27.5-39) years. Eleven patients (52%) were male. Ten patients (48%) had New York Heart Association class I disease, 10 (48%) had class II disease, and 1 (5%) had class III disease. Ejection fraction at initiation was greater than 55% in 11 patients (52%), 35% to 55% in 9 patients (43%), and less than 35% in 1 patient (5%). Prior treatments included β-blockers (71%), sotalol (38%), amiodarone (24%), digoxin (24%), and catheter ablation (38%). Rhythm control was complete in 5 patients (24%), partial in 6 (29%), and inadequate in 10 (48%). Two patients (10%) experienced adverse events, including nausea in 1 (5%) and cardiac arrest in 1 (5%), which occurred 48 months after initiation of treatment. There were no deaths during the follow-up period. The median (IQR) follow-up time for patients with complete or partial rhythm control was 20 (1-54) months.

Conclusion:

Dronedarone can be effective for adult patients with congenital heart disease and atrial arrhythmias for whom more established therapies have failed, and with close monitoring it can be safely tolerated.
Mathematics Teachers' Experiences of Positive Error Climate
Authors: Kalac Senem , Özkaya Merve , Konyalıoğlu Alper Cihan
Published: April 2024

In the qualitative case study in which the question, "What are teachers' views on the applicability of positive error climate in the classroom?" was sought to be answered, 19 mathematics teachers working in different provinces of Turkey, having more than five years of professional experience and receiving master's degree education constituted the study group. Before this study, teachers' attitudes and behaviors toward errors were taken in writing. At the end of the eleven-week implementation, the teachers' opinions about the implementation were obtained through interviews, and content analysis was applied to the data with MAXQDA. 2020. Under the theme of positive error climate experience, teachers evaluated the application as effective, fun, providing permanent learning and increasing self-confidence. On the other hand, they stated the negative aspects as insufficient time, difficulties in classroom management, and causing mislearning. Seventeen participants stated that they would use the error climate in their classrooms.
Arbascular Mycorrhiza and sustainable agriculture: A green approach
Authors: Chowdhury Swapan , Banerjee Mainak , Majumdar Tanmoy
Published: April 2024

Agriculture is new paradigm, sustainable intensification, focuses back on beneficial soil microorganisms for their role in reducing chemical fertilizer and pesticide input and improving plant nutritional and health.More research has been done on arbuscular mycorrhizal fungi (AMF) because they form symbiotic relationships with the root systems of most land plants and make it easier for plants to absorb nutrients by creating extraradical networks of hyphae that spread out from colonized roots into the soil and serve as supplemental absorbents.Plants are protected from abiotic and biotic factors by AMF, and they also contribute in modulating the activity of antioxidant enzymes and secondary metabolites (phytochemicals), including polyphenols, anthocyanins, phytoestrogens and carotenoids.The employment of AMF symbionts to enhance the nutritional and medicinal value of active food items has come under more and more scrutiny in studies.Despite the wide physiological and genetic diversity of plant species, only a few AMFs have been used, thus limiting their full exploitation.This review study concentrates on the results of AMF on plant secondary substance biosynthesis that can improve health, as well as the standards for choosing the best symbionts to be utilized as sustainable biotechnological instruments to create food that is healthy and safe.The main objectives of the articlewas to examine the role AMF plays in improving soil's physical, biological and chemical properties. Regarding the information gaps found in this review, a discussion of potential future research is given. This will improve our understanding of AMF, encourage additional study, and aid in maintaining soil fertility.
Dependence of local carotid arterial stiffness on the presence of atherosclerotic plaque in the carotid basin in hypertensive patients
Authors: Bohun A. O.
Published: April 2024

Aim. To evaluate the viscoelastic properties of the common carotid arteries (CCA) in patients with stage II hypertension (HTN) and to compare these indicators between groups with and without carotid artery (CA) stenosis <50 %.
Materials and methods. The study included 48 patients with stage II HTN, mean age – 55.9 years, 45.8 % men. Basic anthropometric data, laboratory parameters of lipid and carbohydrate metabolism, creatinine, quality intima-media thickness (QIMT), local stiffness indicators: artery diameter, distensibility, distensibility coefficient (DC), compliance coefficient (CC), stiffness indices α, β, local pulse wave velocity (PWV), pressure and augmentation index (using RF-QIMT, RF-QAS technologies) were studied. Statistical analysis was performed, p values of < 0.05 were considered statistically significant.
Results. CA atheromas with stenosis up to 50 % were found in 48 % of the examined, they were older with higher parameters of vessel diameter by 4.6 %, QIMT – by 12.5 %, α index – by 28.0 %, β index – by 27.7 %, and PWV – by 14.7 %. A medium-strength positive correlation has been revealed for age, QIMT, HDL, creatinine level and local stiffness parameters (distensibility, CC, PWV, indices α, β). The atherosclerotic plaque (ASP) presence in the CA was associated with the limit levels of the left CCA QIMT over 698 μm (sensitivity 65.2 %, specificity 86.6 %, p < 0.01), of the right – over 598 μm (sensitivity 73.9 %, specificity 66.6 %, p < 0.01). However, a greater dependence on age than on the presence of atheroma has been proven. At the same time, the odds ratio of the ASP presence was 2.99-fold higher (p = 0.0065) with an increase in the CCA diameter of more than 7.94 mm, and in the multivariate model incorporating age – 2.6-fold higher (p = 0.036), while age has not impacted significantly (p = 0.301) the prognosis.
Conclusions. In individuals with stage II HTN, the presence of CA atherosclerosis with stenosis up to 50 % is associated with a significant increase in vessel diameter regardless of age. CCA intima media thickness depends more on the age of hypertensive patients.
Features of the clinical course of chronic pancreatitis in patients with chronic obstructive pulmonary disease
Authors: Khukhlina O. S. , Dudka I. V. , Dudka T. V.
Published: April 2024

Aim. The purpose of the study is to determine the intensity of the manifestation of clinical syndromes in the comorbid course of chronic pancreatitis (CP) in patients with chronic obstructive pulmonary disease (COPD) in comparison with the isolated course of CP and to assess the intensity of the mutual burden syndrome.
Material and methods. A prospective cohort study was conducted, analyzing the medical records of 212 inpatients. The first group comprised 96 individuals with an isolated course of chronic pancreatitis (CP), while the second group included 116 patients with CP and comorbid chronic obstructive pulmonary disease (COPD), categorized as Group E. The study focused on subjective manifestations of pain syndrome in CP, the extent of exocrine pancreatic insufficiency, clinical blood analysis, biochemical research regarding the content of markers indicating pancreatic enzyme deviation in the blood, and the level of elastase-1 in feces. Additionally, ultrasonographic examination of the organs in the abdominal cavity was performed.
Results. Patients in group 2 exhibited manifestations of abdominal pain syndrome 1.2 times more frequently than those in group 1 (p < 0.05). The frequency of pain in the pancreas radiating to the right subcostal region was 1.9 times higher in group 2 compared to group 1 (p < 0.05), along with a 2.1 times increase in the symptom of girdled pain radiating to the back (p < 0.05). Although the frequency of dyspeptic syndrome was slightly higher in group 2 (1.3 times, p > 0.05), astheno-vegetative syndrome was significantly more pronounced, exceeding the frequency in group 1 by 1.7 times (p < 0.05).
Ultrasonography parameters of the pancreas in both groups revealed characteristic signs of chronic pancreatitis (CP). The analysis of pancreatic functional state indicators during exacerbation indicated hyperenzymemia syndrome, with α-amylase activity significantly higher in patients of both groups compared to the control group – by 1.8 and 2.6 times, respectively (p < 0.05).
Conclusions. CP with chronic obstructive pulmonary disease (COPD) is characterized by a significantly lower frequency of paroxysmal abdominal pain syndrome but a higher frequency of constant aching pain in the pancreas area. Additionally, it is associated with the maximum intensity of inflammation, hyperfermentemia, a decrease in the activity of elastase-1 in feces, and a higher intensity of astheno-vegetative, painful, dyspepsia, intoxication syndromes. Moreover, there is a more pronounced exocrine dysfunction of the pancreas and more significant changes in the sonographic structure of the pancreas compared to cases with the isolated course of CP.
In silico study of properties in the series of 1-alkyl-4-(((5-nitrofuran-2-yl)methylene)amino)- 1,2,4-triazole halides
Authors: Kucherenko L. I. , Brytanova T. S. , Hotsulia A. S.
Published: April 2024

1,2,4-Triazole derivatives open up wide horizons for modern medicinal chemists to develop innovative drugs. The use of 1,2,4-triazole derivatives in pharmacological research is based on their ability to produce an effective effect on biological systems and interact with molecular targets. These azoles can be used to regulate various physiological processes, which opens up the possibility of their effective use in the treatment of various diseases.
Targeted modification of the structure of 1,2,4-triazole derivatives opens up wide opportunities for the creation of biologically active compounds with improved properties, which contributes to further advances in pharmaceutical research and the development of new, effective drugs.
The aim of this work is to predictively assess the pharmacological potential of 1-alkyl-4-(((5-nitrofuran-2-yl)methylene)amino)-1,2,4-triazole halides by in silico studies.
Materials and methods. ADME-analysis is a method of studying the physical-chemical and pharmacokinetic parameters of the studied substances using the online resource SwissADME. Molecular docking is a method of predicting and evaluating the interaction between a ligand molecule and the three-dimensional structure of the target protein. The ligands have been prepared with the software MarvinSketch 6.3.0, Hyper Chem 8, and AutoDockTools-1.5.6, whereas the software packages Discovery Studio 4.0 and AutoDockTools-1.5.6 have been used for the preparation of enzymes. The Vina program was used for direct molecular docking.
Results. A prescreening analysis was conducted on a virtual series of 1-alkyl-4-(((5-nitrofuran-2-yl)methylene)amino)-1,2,4-triazole halides, recognized as potential sources of biologically active substances. The study involved determining the main physicochemical characteristics and unveiling general pharmacokinetic parameters of the molecules. The Vina program was employed to identify the nature and number of amino acid residues in the active sites of model enzymes interacting with the proposed ligands. Results indicate the highest affinity for lanosterol 14α-demethylase. However, the analysis of ligand complexes with cyclooxygenase-2 and anaplastic lymphoma kinase suggests a low probability of a significant effect on these enzymes.
Conclusions. The overall prognosis for bioavailability in the case of oral administration of dosage forms with the investigated substances is favorable. Pharmacodynamics in silico studies allow us to identify 1-heptyl- and 1-octyl-4-(((5-nitrofuran-2-yl)methylene)amino)-1,2,4-triazolium bromides as potential antifungal agents that can reasonably be involved in further in-depth studies of this type of activity.