bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein Interaction Analysis and Molecular Simulation of the Anti‐Inflammatory Activities in Melaleuca cajuputi Extract Against COVID‐19
Authors: Tjiptaningrum Agustyas , Kurniati Intanri , Fadilah Fadilah , Susantiningsih Tiwuk , Prawiningrum Aisyah Fitriannisa , Utari Wahyu Dian , Erlina Linda
Published: November 2024

Coronavirus disease‐19 (COVID‐19) is correlated to a severe condition caused by a cytokine storm during which numerous proinflammatory cytokines, including interleukin‐6 (IL‐6) are released. IL‐6 is a critical driver in the COVID‐19 inflammatory state, and the inhibition is considered a potential treatment approach to prevent serious complications. Meanwhile, Melaleuca cajuputi is a plant with antibacterial, antiviral, anti‐inflammatory, and antioxidant activities. Therefore, this aimed to investigate the anti‐inflammatory potential of M. cajuputi in silico. Extraction of leaves was conducted by using 96% ethanol, followed by fractionation to obtain active compounds. Subsequently, LC/MS and GC/MS analyses were performed to obtain active compound profiling. Protein‐protein interaction (PPI), as well as molecular docking and dynamic analyses, were performed to examine interaction of active compounds of M. cajuputi with IL‐6. The results showed that 30 protein nodes played a significant role in COVID‐19 cytokine storm and eight active compounds had interactions with IL‐6. Among the active compounds, pinostrobin chalcone had the best delta G interaction with IL‐6. In conclusion, M. cajuputi has potential activity as an anti‐inflammatory agent against COVID‐19.
A Robust Displacement Monitoring Model for High‐Arch Dams Integrating Signal Dimensionality Reduction and Deep Learning‐Based Residual Correction
Authors: Zhu Yantao , Niu Xinqiang , Yan Tianyou , Xu Lifu
Published: November 2024

Deformation is a critical indicator for the safety control of high‐arch dams, yet traditional statistical regression methods often exhibit poor predictive performance when applied to long‐sequence time series data. In this study, we develop a robust predictive model for deformation behavior in high‐arch dams by integrating signal dimensionality reduction with deep learning (DL)‐based residual correction techniques. First, the fast Fourier transform is employed to decompose air and water temperature sequences, enabling the extraction of temperature cycle characteristics at the dam boundary. A data‐driven statistical monitoring model for dam deformation, based on actual temperature data, is then proposed. Subsequently, an improved Bayesian Ridge regression model is used to construct the dam deformation monitoring framework. The residuals that traditional statistical methods fail to capture are input into an enhanced Long Short‐Term Memory (LSTM) network to effectively learn the temporal characteristics of the sequence. A high‐arch dam with a history of long‐term service is used as a case study. Experimental results indicate that the data dimensionality reduction method effectively extracts relevant information from observed temperature data, reducing the number of input variables. Comparative evaluation experiments show that the proposed hybrid predictive model outperforms existing state‐of‐the‐art benchmark algorithms in terms of predictive efficiency and accuracy. Additionally, this approach combines the interpretability of statistical regression methods with the powerful nonlinear modeling capabilities of DL‐based models, achieving a synergistic effect.
Monitoring the Overall Quality of Groundwater Using a Geographic Information System in the Angads Plain (Oujda, Morocco)
Authors: Taoufiq Latifa , Kacimi Ilias , Saadi Mohamed , Nouayti Nordine , Kassou Nadia , El-Mouhdi Karima
Published: November 2024

The future of groundwater is one of the key challenges for sustainable water management, hence the need to monitor its overall quality. The objective of this work is to assess the overall quality and determine the spatiotemporal evolution of the Angads aquifer in northeastern Morocco in 2014 and 2020, based on the parameters NH4+, NO3−, EC, Cl−, and FC, as well as the Geographic Information System (GIS). The results of the comparison of these five parameters between 2014 and 2020 show a general increase in NH4+ and a decrease in NO3− and FC at most sampling points. These changes could be attributed to a shift in pollution sources or biological processes affecting water quality. On the other hand, the stability of EC and Cl− levels suggests a consistency in the inputs of salts or minerals. The quality percentages show a decrease in good, poor, and very poor quality, following an increase in average quality, from 10.52% (in 2014) to 5.26% (in 2020), 31.57% (in 2014) to 21.05% (in 2020), 31.57% (in 2014) to 26.31% (in 2020), and 26.31% (in 2014) to 47.36% (in 2020), respectively. Spatial and temporal mapping of the quality over these 2 years shows that the deterioration continues toward the east, southeast, and southwest. This is justified by very high measurements of the parameters NO3−, EC, and Cl− at sampling points 2, 3, 4, 5, 7, 8, and 15 for 2014 and 2020, reaching 156 mg/L, 10,570 µS/cm, and 3790 mg/L in 2014 and 134 mg/L, 10,355 µS/cm, and 3597 mg/L in 2020, respectively, due to effluents from pollution points such as the Oujda public landfill, the wastewater treatment plant, and the former Sidi Yahya landfill to the west. On the other hand, in the north, northeast, and northwest, there has been an improvement in quality due to the remoteness of these pollution points. In order to protect this vital resource, recommendations need to be put in place, in particular by treating leachates so as to ensure that the quality of the water is not discharged directly into the aquifer or used for other purposes, and to avoid discharging effluent from the wastewater treatment plant into the natural environment.
Supplementary Data from The Significance of Comprehensive Metabolic Phenotypes in Cancer Risk: A Japan Multi-Institutional Collaborative Cohort Study
Authors: Watanabe Takeshi , Nguyen Tien Van , Katsuura-Kamano Sakurako , Arisawa Kokichi , Ishizu Masashi , Unohara Taichi , Tanaka Keitaro , Shimanoe Chisato , Nagayoshi Mako , Tamura Takashi , Kubo Yuko , Kato Yasufumi , Oze Isao , Ito Hidemi , Michihata Nobuaki , Nakamura Yohko , Tanoue Shiroh , Koriyama Chihaya , Suzuki Sadao , Nakagawa-Senda Hiroko , Koyama Teruhide , Tomida Satomi , Kuriki Kiyonori , Takashima Naoyuki , Harada Akiko , Wakai Kenji , Matsuo Keitaro
Published: November 2024

Supplementary File (List of the contributors to the J-MICC Study)
Roles of cancer histology type and HPV genotype in HPV ctDNA detection at baseline in cervical cancer: Implications for tumor burden assessment
Authors: Lee Miseon , Lee Eun Ji , Kang Jun , Lee Keun Ho , Lee Sung Jong , Hong Sook Hee , Kim Hee Seung , Lee Ahwon
Published: November 2024

Introduction: Human papillomavirus circulating tumor DNA (HPV ctDNA) is a promising biomarker for monitoring cervical cancer. HPV ctDNA level at baseline (before treatment) reflects tumor burden. However, reported HPV ctDNA detection rates at baseline have shown variations across studies, suggesting the existence of other potential contributing factors. This study aimed to identify additional factors that might influence HPV ctDNA detection at baseline, focusing on histology type and HPV genotypes (high-risk genotypes HPV16 and HPV18).
Methods: We retrospectively analysed blood samples at baseline prior to treatment from 92 patients diagnosed with HPV16- or HPV18-associated cervical cancer (FIGO IA2–IIIC2) between 2013 and 2020. HPV ctDNA was evaluated using digital droplet PCR (ddPCR).
Results: HPV ctDNA was detected at baseline in 41.3% of cases. Locally advanced cervical cancers had a higher (p = 0.028) detection rate at baseline than early stage cervical cancers. HPV ctDNA positivity was significantly (p = 0.048) higher for HPV18 (60%) than for HPV16 (34.3%). Adenocarcinoma/adenosquamous carcinoma had a higher HPV ctDNA detection rate at baseline (54.2%) than squamous cell carcinoma (36.8%), but not significantly (p = 0.212) higher.
Conclusion: This study found the impact of histology and HPV genotype on HPV ctDNA at baseline in cervical cancer. HPV18 and adenocarcinoma were associated with a higher baseline HPV ctDNA detection rate. These results suggest the need for different HPV ctDNA approaches for analyzing tumor burden. This finding may also serve as a useful reference for post-treatment surveillance studies.
The Moorish Body in Resistance
Authors: El Idrissi Zakariae
Published: November 2024

The female Moor of Islamic Spain appeared frequently on the English stage in the seventh and eighteeth centuries; however, the discussion of her character, presence, portrayal and performance on stage has been widely missing in most critical studies on feminine orientalism. The image of Andalusian women in English theatre is very intriguing and worth dealing with since it offers a site where different dimensions combine, interact, intersect and even melt: orientalism, gender politics, theatrical topicality and the Andalus legacy. This article focuses mainly on Sophia Lee’s Almeyda; Queen of Granada (1796) as a female-authored play staging a Moorish heroine. It argues that the Moorish heroine offers a performing experience that goes beyond imperially-oriented drama and conventionally-played oriental roles. Combining notions of orientalism as western self-criticism with Mikhail Bakhtin’s concept of the Romantic grotesque, I try to demonstrate that Almeyda’s body, while inscribed with authority, possesses carnavalesque-like qualities that negotiate gendered western power structures. In a deliberately-made manoeuvre, Almeyda resorts to artificial madness through which she and, by implication, Lee grapple with western patriarchy, promote feminine-oriented rule, transcend neo-classical constraints and undermine Enlightenment reason.
Draining the Past
Authors: Duiveman Adriaan
Published: November 2024

Engineer Johan van Veen is widely regarded as the “father” of the Dutch Delta Works, a series of sea defence structures which protect parts of the Netherlands against storm surges. When the construction started, the plans were unprecedented in scale and wagered on technologies that were not yet invented. Nonetheless, this article shows that Van Veen defended his daring, innovative, and expensive megaproject by telling a narrative about 24 centuries of national, Dutch history. Drawing inspiration from the Narrative Policy Framework developed by policy researchers, it analyses Van Veen’s English-language book Dredge, Drain, Reclaim (1948–1962). Here, the engineer created a plot in which the Delta Works were the logical climax of Dutch history.
A new granite cave dwelling endemic species of the Cyrtodactylus intermedius group (Squamata: Gekkonidae) from Hon Son Island, Kien Giang Province, Vietnam
Authors: TRAN THINH GIA , LAM NGON QUANG , NGUYEN TRUONG MINH NHAT , NGUYEN NGA THI , NGUYEN THAO THI PHUONG , SMITH JACOB , NGUYEN VU DANG HOANG , GRISMER L LEE
Published: November 2024

During field work on Hon Son Island, we discovered a new species of the genus Cyrtodactylus inferred from genetic and morphological evidence. Phylogenetic analyses based on the mitochondrial gene ND2, delimit Cyrtodactylus borgattaorum sp. nov. as a new species in the C. intermedius group and the strongly supported sister species of C. phuquocensis in both Bayesian inference and Maximum Likelihood analyses. The new species is distinguished from all other members of the intermedius group by having the combination of 12 supralabials; 10 or 11 infralabials; 22 or 23 small, rounded, smooth, paravertebral tubercles; 12 rows of small, rounded, smooth, longitudinally arranged body tubercles; 35–39 ventrals; 8–10 expanded subdigital lamellae, 12 or 13 unexpanded subdigital lamellae, and 21 or 22 total subdigital lamellae on the fourth toe; 21 or 22 enlarged femorals; 8 or 9 enlarged precloacals; 8 or 9 precloacal pores in males; three rows of enlarged post-precloacals; postcloacal tubercles; enlarged femorals and enlarged precloacals not continuous; proximal femorals nearly same size of distal femorals; body tubercles smooth, greatly reduced; no pocketing between digits on the hands and feet; two dark-colored pigmented blotches on top of head; four dark-colored dorsal bands lacking lightened centers, thinner than light-colored interspaces between bands, bordered by prominent white tubercles; no dark body markings in light-colored interspaces between bands; limbs bearing white tubercles; and six dark-colored and light-colored caudal bands. Cyrtodactylus borgattaorum sp. nov. lives in syntopy with Cyrtodactylus eisenmanae which is the first record of syntopy between granite cave dwelling Cyrtodactylus.
The first Palearctic species of Discheramocephalus Johnson (Coleoptera, Ptiliidae, Ptiliinae) from Korea with an annotated catalog of the genus Discheramocephalus
Authors: JANG TAEYOUNG , PARK JONG-SEOK
Published: November 2024

Nineteen species of the genus Discheramocephalus Johnson have been identified from the Afrotropical, Australasian, Indomalayan, and Neotropical regions. According to distribution of the previously known species and some undescribed species, Discheramocephalus has been suggested to be a pantropical genus. Herein, the first Palearctic species, Discheramocephalus jaeseoki sp. nov., has been described from the Korean Peninsula. Illustrations of its habitus and diagnostic characters, a distributional map, and an annotated taxonomic catalogue of the genus Discheramocephalus are also provided.
Estimating the causal effect of dexamethasone versus hydrocortisone on the neutrophil- lymphocyte ratio in critically ill COVID-19 patients from Tygerberg Hospital ICU using TMLE method
Authors: Nkuhairwe Ivan Nicholas , Esterhuizen Tonya Marianne , Sigwadhi Lovemore Nyasha , Tamuzi Jacques Lukenze , Machekano Rhoderick , Nyasulu Peter S.
Published: November 2024

Background

Causal inference from observational studies is an area of interest to researchers, advancing rapidly over the years and with it, the methods for causal effect estimation. Among them, Targeted Maximum Likelihood estimation (TMLE) possesses arguably the most outstanding statistical properties, and with no outright treatment for COVID-19, there was an opportunity to estimate the causal effect of dexamethasone versus hydrocortisone upon the neutrophil-lymphocyte ratio (NLR), a vital indicator for disease progression among critically ill COVID-19 patients.

Methods

TMLE variations were used in the analysis. Super Learner (SL), Bayesian Additive Regression Trees (BART) and parametric regression (PAR) were implemented to estimate the average treatment effect (ATE).

Results

The study had 168 participants, 128 on dexamethasone and 40 on hydrocortisone. The mean causal difference in NLR on day 5; ATE [95% CI]: from SL-TMLE was − 0.309 [-3.800, 3.182] BART-TMLE 0.246 [-3.399, 3.891] and PAR-TMLE 1.245 [-1.882, 4372]. The ATE of dexamethasone versus hydrocortisone on NLR was not statistically significant since the confidence interval included zero.

Conclusion

The effect of dexamethasone is not significantly different from that of hydrocortisone on NLR in critically ill COVID-19 patients admitted to ICU. This implies that the difference in effect on NLR between the two drugs is due to random chance. TMLE remains an outstanding approach for causal analysis of observational studies with the ability to be augmented with multiple prediction approaches.
Effect of linex treatment on IFN-γ and IL-4 in mice infected with Trichinella
Authors: Atta Shimaa Attia , Fahmy Zeinab H. , Selim Eman A.H. , Aboushousha Tarek , Mostafa Reham Refaat
Published: November 2024

Trichinellosis is a zoonotic, foodborne parasitic infection causing muscle damage. This study investigated the potential therapeutic effects of the commercially available probiotic treatment Linex, both alone and in combination with Albendazole (ALB), on the intestinal and muscular stages of Trichinella spiralis infection in mice, assessing outcomes through parasitological, immunological, and histopathological measures. This study is the first to demonstrate the synergistic effect of combining the commercially available probiotic Linex with Albendazole for trichinellosis treatment. By enhancing both parasitological and immunological outcomes, this combined therapy not only significantly reduces parasite burden but also modulates the immune response, shifting it toward a protective Th1 profile. In parasitological terms, the highest adult and larval count reduction was observed in combined Linex and Albendazole treatment (100%, 97.7%) respectively. Lesser percentage of reduction were recorded in Linex alone therapy (43.2%, 88.4%) respectively. Histopathologically there was amelioration of the inflammatory cellular infiltration in all treated groups with best results in combined Linex and Albendazole treatment. Immunologically, serum IFN-γ levels increased significantly in all treated groups with highest levels in combined Linex and Albendazole treatment, while IL-4 and IL-13 level decreased significantly in all treated groups with best results observed in Linex alone treatment. To conclude; combined Linex and Albendazole treatment of mice infected with T. spirals could ameliorate the infection and improve the immune response.
Three-dimensional digital imaging analysis of the palatal bone thickness for orthodontic mini-implant insertion – determination of the safe zone and angulation
Authors: Schubert Hanna , Matta Ragai , Seidel Anna , Adler Werner , Wichmann Manfred , Kesting Marco , Lutz Rainer
Published: November 2024

Background

In order to successfully perform orthodontic mini-implant procedures successfully for the subsequent anchoring of orthodontic appliances, it is crucial to know the palatal bone thickness. This is usually assessed using two-dimensional radiographs. The purpose of this study was to use a three-dimensional digital imaging measurement method to provide information on palatal bone volume and bone thickness and to make recommendations on the optimal and safe insertion site and angle for palatal mini-implants.

Methods

For this observational, cross-section study, pre-existing cone beam computed tomography scans of 184 patients were converted into 3D Standard Tessellation Language (STL) models of the maxilla. The area between the canine and the first molar was divided into 6 regions of interest (ROIs), three on the left side of the palate and three on the right side. The bone thickness of the palate was analyzed volumetrically and linearly while simulating different mini-implant insertion angles of 0°, 10°, 20° and 30° degrees relative to the palatal surface.

Results

Among the ROIs, the greatest mean bone thickness was observed in the region of the first premolars with a mean distance (MD) of 10.44 ± 2.53 mm and decreased from anterior to posterior (MD: 3.44 ± 1.16 mm). The highest volume (Vol) values were also measured in the anterior palatal region (Vol: 1127.26 ± 483.91 mm3), while there was also a decrease in the posterior region (Vol: 394.36 ± 180.22 mm3). Regarding the simulated palatal mini-implant insertion sites, the greatest bone thickness was found in the anterior region, at the level of the canines with an angle of 0° (MD: 12.25 ± 3.75 mm). In the more posterior region, at the level between the first and second premolars, the greatest bone thickness was observed at an angle of 30° (MD: 7.93 ± 3.81 mm). Gender differences were found.

Conclusion

This clinical study showed that the paramedian region at the level of the first premolar is the safest site for orthodontic mini-implant placement as evaluated by three-dimensional measurements. The results showed that implant insertion angle, gender and age are important aspects to consider when planning and inserting orthodontic palatal mini-implants.

Trial registration

N.a.
Fear of progression in patients with acute myocardial infarction: a cross-sectional study
Authors: Wang Xinghui , Jiang Nan , Chen Shuoxin , Tuerdi Subinuer , Yang Jiayu , Yan Rong , He Li , Wang Jiajia , Li Yuewei
Published: November 2024

Background

Acute myocardial infarction (AMI) is the most serious manifestation of coronary artery disease. At present, existing treatments cannot change the risk factors for the occurrence of the disease, so patients are prone to fear of progression or recurrence, and studies have shown that excessive fear will cause patients to over-examine, mental abnormalities, suicide and other behaviors, increase unnecessary medical care costs and the social medical burden. Thus to investigate the current situation of progression fear in patients with Acute Myocardial Infarction (AMI) admitted to hospital in stable stage and analyze its influencing factors.

Methods

This is a cross-sectional study. In this study, 160 AMI patients admitted to the Department of Cardiology of a 3 A hospital in Changchun from November 2022 to April 2023 were selected as the research sample by a convenient sampling method. Patients completed the general information questionnaire, the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), the Brief Illness Perception Questionnaire (BIPQ), the Medical Coping Modes Questionnaire (MCSQ), the Social Support Rating Scale (SSRS), and the Positive Psychological Questionnaire (PPQ) at the time of stable condition. Using SPSS 25.0 software for data analysis, statistical methods mainly include descriptive statistics, analysis of variance, Pearson correlation analysis and multiple linear regression analysis.

Results

A total of 160 subjects were included, among which the score of simplified fear of progression scale was (33.43 ± 7.09), and the incidence of disorder of fear of progression was 50.60%. The influencing factors included gender (Beta = 0.118, P<0.05), disease perception (Beta = 0.445, P<0.001), psychological capital (Beta=-0.252, P<0.05) and resignation (Beta = 0.167, P < 0.05).

Conclusion

The overall level of fear of progression in patients with AMI at the stable stage of hospitalization is above the medium level. Nursing staff should focus on AIM patients suffering from multiple diseases and lacking awareness of their own diseases, and provide personalized health guidance and psychological nursing targeted to improve patients’ rehabilitation, quality of life and FoP level.
Characterizing the pharmacological interaction of the antimalarial combination artefenomel-piperaquine in healthy volunteers with induced blood-stage Plasmodium falciparum to predict efficacy in patients with malaria
Authors: Abd-Rahman Azrin N. , Kaschek Daniel , Kümmel Anne , Webster Rebecca , Potter Adam J. , Odedra Anand , Woolley Stephen D. , Llewellyn Stacey , Webb Lachlan , Marquart Louise , Chalon Stephan , Gaaloul Myriam El , McCarthy James S. , Möhrle Jörg J. , Barber Bridget E.
Published: November 2024

Background

The combination antimalarial artefenomel-piperaquine failed to achieve target efficacy in a phase 2b study in Africa and Vietnam. We retrospectively evaluated whether characterizing the pharmacological interaction of this antimalarial combination in a volunteer infection study (VIS) would have enabled prediction of the phase 2b study results.

Methods

Twenty-four healthy adults enrolled over three consecutive cohorts were inoculated with Plasmodium falciparum-infected erythrocytes on day 0. Participants were randomized within each cohort to one of seven dose combination groups and administered a single oral dose of artefenomel-piperaquine on day 8. Participants received definitive antimalarial treatment with artemether-lumefantrine upon parasite regrowth or on day 42 ± 2. The general pharmacodynamic interaction (GPDI) model implemented in the Bliss Independence additivity criterion was developed to characterize the pharmacological interaction between artefenomel and piperaquine. Simulations based on the model were performed to predict the outcomes of the phase 2b combination study.

Results

For a dose of 800 mg artefenomel administered with 640 mg, 960 mg, or 1440 mg piperaquine, the simulated adequate parasitological response at day 28 (APR28), incorporating actual patient pharmacokinetic (PK) data from the phase 2b trial, was 69.4%, 63.9%, and 74.8%, respectively. These results closely matched the observed APR28 in the phase 2b trial of 67.0%, 65.5%, and 75.4%, respectively.

Conclusions

These results indicate that VIS offer an efficient means for informing antimalarial combination trials conducted in the field, potentially expediting clinical development.

Trial registration

This study was registered on ClinicalTrials.gov on 11 May 2018 with registration number NCT03542149.
Facilitators and challenges in collaboration between public health units and faith-based organizations to promote COVID-19 vaccine confidence in Ontario
Authors: Kadio Kadidiatou , Blake-Hepburn Denessia , Song Melodie Yunju , Karbasi Anna , Noad Elizabeth Estey , Abdi Samiya , Peer Nazia , Fadel Shaza A. , Allin Sara , Ataullahjan Anushka , Di Ruggiero Erica
Published: November 2024

Background

Equitable access to vaccination remains a concern, particularly among population groups made structurally vulnerable. These population groups reflect the diversity of communities that are confronted with structural barriers caused by systemic racism and oppression and result in them experiencing suffer disadvantage and discrimination based on citizenship, race, ethnicity, ancestry, religion, spiritual beliefs, and/or gender identity. In Canada, Ontario public health units (PHUs) engage with faith-based organizations (FBOs) to improve vaccine confidence among populations made structurally vulnerable. This study explores the factors that facilitate and hinder engagement in the implementation of vaccine confidence promoting interventions, and challenges associated with working with FBOs.

Methods

In-depth interviews were conducted with 18 of the 34 Ontario PHUs who expressed an interest. Braun and Clarke’s “experiential” approach was used to explore the realities of PHUs’ contextual experiences and perspectives.

Results

The results showed that receptivity and openness of PHUs to learn from FBOs, previous experience working with religious communities and FBOs, ongoing relations based on respect of different beliefs and opinions on the vaccines, leveraging the support of trusted faith leaders among communities and communications strategy adapted and sensitive to the needs of the community was facilitators to community involvement in the prevention and control of COVID-19. On the other hand, factors both internal and external to the PHUs have often posed challenges to collaboration with the FBOs. Internal factors include low operational capacity of PHU like insufficient human and financial resources, weak analytical capacity, ambiguity in the roles and responsibilities of the different actors. Some external challenges issues were related to the provincial level and the Ministry of Health, while others were related to FBOs. For example, faith-based and collective beliefs promoting vaccine hesitancy have resulted in resistance from some religious communities when PHUs have reached out to collaborate.

Conclusions

Engaging with faith-based communities is an ongoing process that requires time, flexibility, and patience, but it is necessary to improve vaccine confidence and equity access among population groups made structurally vulnerable. Lessons learned from this research can guide the implementation of future vaccination programs.
INSIGHT-2: mechanistic studies into pregnancy complications and their impact on maternal and child health—study protocol
Authors: Valensin Carlotta , Côté Emilie J. M. , Pereira-Carvalho Daniela , Gardner Rachael A. , Nishku Glen , Giles Caitlin L. , Gill Carolyn , Brockbank Anna , Story Lisa , Shennan Andrew H. , Suff Natalie , Gibbons Deena L. , Tribe Rachel M.
Published: November 2024

Background

Pregnancy and early childhood cohorts provide a framework for investigating the complex interplay between early-life exposures and health outcomes, thereby informing prevention strategies and interventions to improve maternal and child health. In this paper, we outline the objectives, methodologies and expected contributions of INSIGHT-2, a comprehensive cohort study dedicated to advancing our understanding of pregnancy and pregnancy complications towards improving the health and well-being of mothers and their offspring.

Methods

Over the course of 5 years, the study aims to establish a diverse cohort of 1700 pregnant women and to follow up their children up to 2 years of age. Recruitment targets participants with healthy pregnancies, preexisting conditions, and/or risk factors for pregnancy complications or later child health problems. Clinical and lifestyle data and a range of biological samples will be collected, providing a comprehensive resource for biomarker investigations and cross-sectional analyses. It is anticipated that the cohort will continue beyond this initial 5-year plan.

Discussion

By gathering a wide range of biological samples and using diverse analytical techniques, this study supports broad participation, potential replication and collaboration across various sites. The extensive collection of longitudinal data and samples not only facilitates current investigations but also establishes a biobank for future research. The exploration of pre-pregnancy and pregnancy factors that may contribute to disease processes and impact fetal well-being and future health will provide a comprehensive picture of disease mechanisms in both mothers and children, facilitating the identification of biomarkers for the prediction, diagnosis, and management of pregnancy complications. Additionally, our diverse population allows for the capture of various pregnancy complications and outcomes, enhancing external validity and addressing health disparities. This comprehensive design ultimately aims to improve maternal and child health outcomes by providing a valuable longitudinal study of the relationships among the in utero environment, pregnancy management, and long-term maternal and child health, ensuring that findings are relevant and beneficial to a broader population.
A therapeutic approach to pantothenate kinase associated neurodegeneration: a pilot study
Authors: Pereira Alessandra , Fischinger Moura de Souza Carolina , Álvarez-Córdoba Mónica , Reche-López Diana , Sánchez-Alcázar José Antonio
Published: November 2024

Background

Neurodegeneration with brain iron accumulation (NBIA) is a group of genetic neurological disorders frequently associated with iron accumulation in the basal nuclei of the brain characterized by progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. Pantothenate kinase-associated neurodegeneration (PKAN) is one of the most widespread NBIA disorders. The diagnosis of PKAN is established with clinical features and the “eye of the tiger” sign identified on brain MRI and the identification of biallelic pantothenate kinase 2 (PANK2) pathogenic variants on molecular genetic testing. PANK2 catalyzes the first reaction of coenzyme A (CoA) biosynthesis, thus, altered PANK2 activity is expected to induce CoA deficiency as well as low levels of essential metabolic intermediates such as 4′-phosphopantetheine which is a necessary cofactor for critical proteins involved in cytosolic and mitochondrial pathways such as fatty acid biosynthesis, mitochondrial respiratory complex I assembly and lysine and tetrahydrofolate metabolism, among other metabolic processes.

Methods

In this manuscript, we examined the effect of a multitarget complex supplements (pantothenate, pantethine, omega-3 and vitamin E) on in vitro patient-derived cellular models and the clinical outcome of the adjuvant supplements in combination with the baseline neurological medication in three PKAN patients.

Results

Multitarget complex supplements significantly reduced iron accumulation and increased PANK2 and ACP expression levels in the cellular models derived from all three PKAN patients. In addition, the adjunct treatment to the standard neurological medication improved or stabilized the clinical symptoms of patients.

Conclusions

Our results suggest that multitarget complex supplements can be clinically useful as augmentation therapy for PKAN patients harboring pathogenic variants with residual enzyme levels.

Trial registration: CAAE: 58219522.6.0000.5330. Registered 25 May 2022—Retrospectively registered, https://plataformabrasil.saude.gov.br/visao/pesquisador/gerirPesquisa/gerirPesquisaAgrupador.jsf.
TGFβ family signaling in human stem cell self-renewal and differentiation
Authors: Liu Sijia , Ren Jiang , Hu Yanmei , Zhou Fangfang , Zhang Long
Published: November 2024

Human stem cells are undifferentiated cells with the capacity for self-renewal and differentiation into distinct cell lineages, playing important role in the development and maintenance of diverse tissues and organs. The microenvironment of stem cell provides crucial factors and components that exert significant influence over the determination of cell fate. Among these factors, cytokines from the transforming growth factor β (TGFβ) superfamily, including TGFβ, bone morphogenic protein (BMP), Activin and Nodal, have been identified as important regulators governing stem cell maintenance and differentiation. In this review, we present a comprehensive overview of the pivotal roles played by TGFβ superfamily signaling in governing human embryonic stem cells, somatic stem cells, induced pluripotent stem cells, and cancer stem cells. Furthermore, we summarize the latest research and advancements of TGFβ family in various cancer stem cells and stem cell-based therapy, discussing their potential clinical applications in cancer therapy and regeneration medicine.
A lightweight approach to real-time speaker diarization: from audio toward audio-visual data streams
Authors: Kynych Frantisek , Cerva Petr , Zdansky Jindrich , Svendsen Torbjørn , Salvi Giampiero
Published: November 2024

This manuscript deals with the task of real-time speaker diarization (SD) for stream-wise data processing. Therefore, in contrast to most of the existing papers, it considers not only the accuracy but also the computational demands of individual investigated methods. We first propose a new lightweight scheme allowing us to perform speaker diarization of streamed audio data. Our approach utilizes a modified residual network with squeeze-and-excitation blocks (SE-ResNet-34) to extract speaker embeddings in an optimized way using cached buffers. These embeddings are subsequently used for voice activity detection (VAD) and block-online k-means clustering with a look-ahead mechanism. The described scheme yields results similar to the reference offline system while operating solely on a CPU with a low real-time factor (RTF) below 0.1 and a constant latency of around 5.5 s. In the next part of the work, our research moves toward much more demanding and complex real-time processing of audio-visual data streams. For this purpose, we extend the above-mentioned scheme for audio data processing by adding an audio-video module. This module utilizes SyncNet combined with visual embeddings for identity tracking. Our resulting multi-modal SD framework then combines the outputs from audio and audio-video modules by using a new overlap-based fusion strategy. It yields diarization error rates that are competitive with the existing state-of-the-art offline audio-visual methods while allowing us to process various audio-video streams, e.g., from Internet or TV broadcasts, in real-time using GPU and with the same latency as for audio data processing.
Enhancing aquifer protective capacity prediction over Ibeator and environ, Southeastern Nigeria using artificial neural networks and multivariate linear regression analysis
Authors: Usman Ayatu Ojonugwa , Akakuru Obinna Chigoziem , Azuoko George-Best , Abraham Ema Michael , Chinwuko Augustine Ifeanyi , Chizoba Chima Joshua
Published: November 2024

Aquifer protection is essential for securing a sustainable supply of clean water. This study integrates an artificial neural network (ANN) model, identifying non-linear connections, with multivariate linear regression (MLR) analysis to improve predictions of aquifer protective capacity and assess vulnerability. Twelve vertical electrical soundings (VES) were conducted with a maximum electrode spacing of 250 m. Aquifer parameters derived from the VES dataset were analyzed using ANN to capture complex patterns. The ANN model, trained on historical data, learned the relationship between input variables and protective capacity. MLR analysis identified influential factors affecting vulnerability. Results reveal varying aquifer depths, with Umudime being the deepest and western parts having the shallowest depths. The resistivity map shows high values around Okorobi and Uhuala and low values in eastern to northeastern parts. Hydraulic conductivity and 3D subsurface models exhibit an inverse relationship with resistivity. Transmissivity and storativity maps exhibit similar patterns. MLR outperforms ANN in predicting resistivity, transmissivity, and storability, indicating high forecasting accuracy for aquifer protective capacity. Input parameters' contribution levels follow a specific order for different aquifer properties. R2 Value 0.0869, indicating a weak correlation between the predicted and actual values in ANN model while R2 Value 0.9775 in MLR model shows a strong correlation and much better performance than the ANN model. The results of the modeling suggest that both the ANN and MLR models have shown promising effectiveness and accuracy in predicting aquifer parameters, aiding decision-makers in implementing targeted protection measures, predicting aquifer parameters, providing insights for effective management strategies.
Statistical consulting guidelines for new researchers in psychiatry and mental health – beyond ChatGPT
Authors: Lovik Anikó , Dusseldorp Elise
Published: November 2024

Until recently, statistical consultants did not have to worry about being replaced by artificial intelligence. There was no statistical analogue to ‘Dr Google’ before ChatGPT arrived on the scene. Although ChatGPT (most of the time) adequately responds to basic queries such as the assumptions of different statistical tests or summarises relevant manuals on statistical software providing clear instructions with point-and-click software such as SPSS, there are many important aspects of statistical consulting that ChatGPT does not cover. This tutorial article is about these aspects: a summary of what statistical consulting is, its purpose and possible settings during the empirical research cycle, the role and responsibilities of the consultant and the client, how to ensure a good consulting experience, how to prepare for a consulting session, typical questions and more. The article was written for researchers who are considering contacting a statistician for the first time and aims to facilitate a good and fruitful consulting experience for all parties involved.
País das Maravilhas
Authors: Rebelo Júlia Pereira , Oliveira Edirley Rodrigues de , Monteiro Igor Angelo , Ferreira Paulo Afonso de Alcântara , Souza Rodrigo Valadão de
Published: November 2024

Este caso de ensino aborda os dilemas éticos vivenciados por um dos candidatos ao cargo de prefeito do município fictício País das Maravilhas durante a corrida eleitoral. A personagem central da história é o prefeito, que se vê diante de desafios éticos a serem enfrentados em decisões que podem impactar diretamente sua possibilidade de reeleição. O dilema do prefeito e as consequências de suas escolhas servirão de base para a discussão sobre integridade e ética na gestão pública, e também sobre questões como legalidade, importância da estabilidade do servidor público estatutário e o papel dos órgãos de controle no bom funcionamento da Administração Pública.
Jogo de empurra
Authors: Rocha Alessandro Lima da , Figueiredo Liliane , Neves Rodrigo
Published: November 2024

Informamos que as notas de ensino dos casos possuem acesso restrito e são exclusivas para docentes e instrutores vinculados à uma instituição acadêmica. Saiba mais.
Elaboration and local validation of Entrustable Professional Activities in Palliative Care for resident doctors
Authors: Musy Leitão Sarah , Barros de Vasconcelos Davi José , Vasconcelos Mapurunga Marcelo , Autran Coelho Peixoto Raquel , Aires Peixoto Junior Arnaldo
Published: November 2024

The use of reliable professional activities (EPAs) can help identify which competences each resident doctor should develop during their training in palliative care (PC). The aim of this study was to elaborate and locally validate the titles of the PC EPAs in a teaching hospital in the north-east of Brazil. Of the 25 experts invited, 20 took part in the survey. The initial list of EPA titles was based on a free translation of a list of EPAs from the American Academy of Hospice and Palliative Medicine. The modified e-Delphi method was used for validation. A quantitative Likert 1-4 scale on the importance of each EPA, analyzed using the content validity index (CVI), was used, followed by a validated qualitative 0-5 scale called Quality of EPA (QUEPA) and an open field for suggestions for each EPA. The EPA was approved if the CVI was > 0.8, and of good quality if the average QUEPA score was > 4. The records in the open fields were assessed qualitatively. It was possible to draw up and validate a list of 19 titles of PC EPAs for medical residents, which could help in the training and the assessment of these professionals.
Desenvolvimento de ferramentas educacionais para implantação de Aprendizagem Baseada em Problemas em grandes grupos.
Authors: Brasil de Carvalho Rocha Priscila , Bezerra Bonfim Débora Raquel , Saraiva Leão Câmara Teles Raissa Maria , Maia Beatris , Marçal Edgar , Kubrusly Marcos , Aires Peixoto Junior Arnaldo
Published: November 2024

As metodologias ativas de ensino têm sido cada vez mais empregadas na educação médica. Entretanto, o desafio quanto a essas metodologias, entre elas, a Aprendizagem Baseada em Problemas (ABP), envolve questões logísticas e econômicas. Este estudo objetivou desenvolver ferramentas educacionais para uso em sessões de ABP em grandes grupos. A primeira fase do estudo foi o desenvolvimento dos softwares iTutoria Professor e iTutoria Estudante, seguida pela elaboração de um manual para aplicação desta metodologia. O primeiro foi desenvolvido com ferramenta tipo WebView, acessada via internet e utilizada pelo docente para postagens, e o segundo sob forma de aplicativo para uso pelos discentes durante sessões de tutoria. Em seguida, foi desenvolvido um manual em e-Book para orientar docentes sobre aplicação do ABP em grandes grupos. Os softwares foram avaliados quanto à usabilidade pelo instrumento System Usability Scale (SUS), e sua aceitação através de questionário baseado no Modelo de Aceitação de Tecnologia (TAM). Participaram do estudo 36 discentes aleatoriamente escolhidos, que cursavam do terceiro ao sexto semestre do curso de medicina de um centro universitário, durante o período de novembro de 2021. A usabilidade da plataforma foi considerada boa, com um escore SUS médio igual a 70,1 e considerada com uma usabilidade e aceitação boa, tendo um potencial para o uso em sessões tutoriais, com aplicação de recursos de multimídia como vídeos e sons. O manual desenvolvido também poderá futuramente ser utilizado para treinamento docente e aplicação desta metodologia.
Análise comparativa de simuladores para treinamento em cirurgia oftalmológica
Authors: Dionizio Maria natalia , Vivian Cruz  , Julia Dias  , Jorge Eldo  , João Crispim
Published: November 2024

Este estudo teve como objetivo comparar os simuladores para treinamento em cirurgia oftalmológica, abordando os aspectos funcionais de cada marca. A pesquisa foi conduzida por meio da coleta de informações sobre cada simulador, por meio de documentação técnica e sites de fornecedores, que foram sintetizados em uma tabela, na qual destacou-se os pontos principais de cada marca. Os resultados mostraram que os simuladores analisados demonstram uma variabilidade considerável em termos de realismo e na gama de procedimentos que podem ser simulados. Com base nesses achados, concluiu-se que a escolha do simulador adequado deve considerar fatores como o nível de experiência do cirurgião, o tipo de procedimento a ser simulado, e as restrições orçamentárias.
Atendimento e Dispensação de PrEP na Clínica Escola de Saúde Unichristus
Authors: Mesquita Teixeira Maria das Graças Rafaela , Barbosa Oliveira Jefferson Renêe , Freire de Figueirêdo Filho Daniel , De Melo Desidério Miguel , Martins Lopes Djalma Victor , Rocha Diogenes Pessoa Matheus , Pinheiro Ibiapina Amanda , Barbosa Macedo Italo , Medeiros Melissa Soares
Published: November 2024

A Profilaxia Pré-Exposição (PrEP) ao HIV tem-se consolidado como uma estratégia eficaz de prevenção do HIV, especialmente entre populações de risco elevado. Este estudo apresenta uma análise retrospectiva da experiência de uso da PrEP na Clínica Escola de Saúde da Unichristus (CES), um ambulatório que atua tanto no atendimento de pacientes que buscam a PrEP quanto como unidade dispensadora de medicamentos para setores públicos e privados. Foram analisados 621 pacientes ativos que receberam PrEP até julho de 2024, sendo 607 do sexo masculino, 9 do sexo feminino e 1 mulher transgênero, com média de idade de 35,5 anos (variando entre 18 e 77 anos). A faixa etária predominante é de 20 a 40 anos, representando, aproximadamente, 45% dos pacientes. Destes pacientes, 378 continuam recebendo medicação até junho/2024. A CES acompanhou 186 pacientes sendo 129 ativos, realizado com farmacêuticos e infectologistas. Durante todo o período, 57 pacientes (30,6%) descontinuaram na CES, com uma média de 11,2 meses de uso. A descontinuação de PrEP foi estatisticamente menor entre pacientes acompanhados na CES em relação aos externos (p=0,0053). Conclui-se que o uso de Prep aumentou ao longo dos anos, sendo o predomínio entre usuários do sexo masculino e adultos jovens, além de o acompanhamento na CES ter um menor índice de descontinuação.
Πολιτική γης και αγροτικά συστήματα
Authors: Λένη Σοφία
Published: November 2024

Η αστική διάχυση, η οποία χαρακτηρίζεται από χαμηλή πυκνότητα κτισμένης επιφάνειας, υψηλή εξάρτηση από το αυτοκίνητο και εκτεταμένη κατανάλωση γης, αποτελεί παγκόσμιο φαινόμενο. Η ανεξέλεγκτη εξάπλωση των αστικών περιοχών σε αγροτικές και φυσικές εκτάσεις οδηγεί σε περιβαλλοντική υποβάθμιση, αυξημένα κόστη υποδομών και κοινωνικές ανισότητες, επηρεάζοντας τις χρήσεις/κάλυψη γης και την αειφορία των αστικών κέντρων. Σκοπός της διατριβής και κύριο ερευνητικό ερώτημα αποτελεί η διεξοδική διερεύνηση της ύπαρξης αστικής διάχυσης στα μεσαία ελληνικά αστικά κέντρα και ειδικότερα, στο Πολεοδομικό Συγκρότημα Πατρών και στην ευρύτερη περιοχή του. Ως περίοδος διερεύνησης επιλέχθηκε το διάστημα από το 1981 έως και το 2015, μια περίοδος έντονων μετασχηματισμών στην διάρκεια της οποίας η πόλη βίωσε ραγδαίες αλλαγές αναφορικά με την εμφάνιση, τη δομή και τη λειτουργία της. Στους επιμέρους στόχους συμπεριλαμβάνονται η μέτρηση της αστικής διάχυσης στην περιοχή μελέτης με διαφορετικές μεθοδολογίες ώστε να εξεταστεί η αποτελεσματικότητα αλλα και η συμβολή της κάθε μεθόδου, ο καθορισμός του χωρικού μοτίβου και ο προσδιορισμός των κυρίων τάσεων της αστικής διάχυσης, η ανάλυση των αλλαγών στις χρήσεις/κάλυψη γης και ιδιαίτερα στην αγροτική γη, ο προσδιορισμός των κινητήριων δυνάμεων της αστικής διάχυσης μέσω ημι-δομημένων συνεντεύξεων με προνομιακούς συνομιλητές δίνοντας έμφαση στις χωρικές και χρονικές διαστάσεις της αστικής διάχυσης και τέλος, η διερεύνηση της αλληλεπίδρασης των κινητήριων δυνάμεων και η ποσοτική αξιολόγηση της συμβολής της κάθε κινητήριας δύναμης στο διάστημα των τριαντατεσσάρων ετών, μέσω της ανάλυσης παλινδρόμησης. Η ανάλυση πραγματοποιείται με τη χρήση των Γεωγραφικών Συστημάτων Πληροφοριών (GIS) τα οποία αποτελούν το κατάλληλο περιβάλλον για τη δημιουργία, την αποθήκευση, την ανάλυση και την οπτικοποίηση των γεωχωρικών πληροφοριών που χρησιμοποιούνται στη διατριβή, διαθέτουν τα κατάλληλα εργαλεία για την ανίχνευση και παρακολούθηση των χωρικών αλλαγών και διευκολύνουν την διερεύνηση των χωρικών σχέσεων, των προτύπων και των τάσεων επιτρέποντας την παρακολούθηση και την αξιολόγηση της αστικής διάχυσης και των αλλαγών στις χρήσεις/κάλυψη γης.