bluuebunny/crossref_metadata_2025 huggingface dataset:
Objective wearable measures and subjective questionnaires for predicting response to neurostimulation in people with chronic pain
Authors: Heros Robert , Patterson Denis , Huygen Frank , Skaribas Ioannis , Schultz David , Wilson Derron , Fishman Michael , Falowski Steven , Moore Gregory , Kallewaard Jan Willem , Dehghan Soroush , Kyani Anahita , Mansouri Misagh
Published: June 2023

Background

Neurostimulation is an effective therapy for treating and management of refractory chronic pain. However, the complex nature of pain and infrequent in-clinic visits, determining subject’s long-term response to the therapy remains difficult. Frequent measurement of pain in this population can help with early diagnosis, disease progression monitoring, and evaluating long-term therapeutic efficacy. This paper compares the utilization of the common subjective patient-reported outcomes with objective measures captured through a wearable device for predicting the response to neurostimulation therapy.

Method

Data is from the ongoing international prospective post-market REALITY clinical study, which collects long-term patient-reported outcomes from 557 subjects implanted by Spinal Cord Stimulator (SCS) or Dorsal Root Ganglia (DRG) neurostimulators. The REALITY sub-study was designed for collecting additional wearables data on a subset of 20 participants implanted with SCS devices for up to six months post implantation. We first implemented a combination of dimensionality reduction algorithms and correlation analyses to explore the mathematical relationships between objective wearable data and subjective patient-reported outcomes. We then developed machine learning models to predict therapy outcome based on the subject’s response to the numerical rating scale (NRS) or patient global impression of change (PGIC).

Results

Principal component analysis showed that psychological aspects of pain were associated with heart rate variability, while movement-related measures were strongly associated with patient-reported outcomes related to physical function and social role participation. Our machine learning models using objective wearable data predicted PGIC and NRS outcomes with high accuracy without subjective data. The prediction accuracy was higher for PGIC compared with the NRS using subjective-only measures primarily driven by the patient satisfaction feature. Similarly, the PGIC questions reflect an overall change since the study onset and could be a better predictor of long-term neurostimulation therapy outcome.

Conclusions

The significance of this study is to introduce a novel use of wearable data collected from a subset of patients to capture multi-dimensional aspects of pain and compare the prediction power with the subjective data from a larger data set. The discovery of pain digital biomarkers could result in a better understanding of the patient’s response to therapy and their general well-being.
Toxicity assessment of Phlogacanthus thyrsiflorus, a traditionally used anthelmintic plant of India
Authors: Deori Khirod , Soren Amar Deep , Yadav Arun K.
Published: June 2023

Background

The leaves of Phlogacanthus thyrsiflorus are used as an anthelmintic remedy by the tribes of upper Assam. This study evaluates its toxic effects in laboratory bred mice and rats. Mice were orally dosed for 5 days, whereas rats were dosed for 28 days and variations in behaviour, feeding habits and blood parameters were recorded. The vital organs were processed for histopathology to observe any alternations from normal architecture.

Results

No mortality or adverse toxic effects were manifested in this assessment. Evaluated parameters, namely feeding behaviour, body weights and relative organ weights, appeared to be similar to the control animals. Also, the haematological and serum biochemical parameters and histopathological studies revealed normal results.

Conclusions

The study indicates that P. thyrsiflorus may not be capable of causing toxic effects in mice and rats, and hence, its traditional use as an anthelmintic could be continued. However, other studies to further validate this may be carried out.
Synchronous bilateral idiopathic external auditory canal cholesteatoma: a case report and review of the literature
Authors: Klopper Gerhard Johan , Favara Claudio
Published: June 2023

Background

External auditory canal cholesteatoma (EACC) is a rare pathological condition representing 0.1% of all new otologic cases. Bilaterality manifests in 10% of EACC cases. Similar disease processes include keratosis obturans (KO) and benign necrotizing otitis externa (BNOE). Diagnostic differentiation may not always be unexacting but does however influence management and eventual outcome. This study aims to briefly review the literature, describe an unusual case of synchronous bilateral primary EACC, and simplify the diagnostic challenges surrounding this disease.

Case presentation

A 66-year-old man with no relevant family history, no concurrent or intercurrent illnesses, having undergone no relevant surgery, and had visited the Department of Otorhinolaryngology regarding right-sided otorrhoea and aural pruritis 9 years ago. At the time, he was diagnosed clinically with KO. Nine years later after having defaulted follow-up, he presented again with the same symptoms. Oto-microscopy now revealed excavation of the posterior canal wall, keratinous desquamation, and an intact tympanic membrane. Oto-endoscopy demonstrated extension posteriorly into the mastoid segment of the temporal bone. Computed tomography evinced a soft tissue attenuating mass within the excavated sub-adjacent bone, with extension into the mastoid air cell system. The contralateral ear had a smaller epithelial defect of the canal floor with underlying tympanic plate erosion. A closed mastoidectomy with the reconstruction of the posterior canal wall was performed on the right ear. The left ear was managed conservatively with micro-suctioning and aural toilette. Six months post-surgery, however, the reconstructed posterior canal wall underwent necrotic breakdown. The contralateral lesion gradually progressed into a Naim et al. (2005) Stage III EACC.

Conclusion

This case illustrates the diagnostic challenge presented by EACC and is unusual regarding its bilaterality. The importance of diagnostic differentiation, both in the management of this disease and in the prevention of its progression, is highlighted. The idea of oto-endoscopy as a routine clinical tool is introduced, and endoscopic images are compared to high-definition computed tomography scans of the affected temporal bones.
Evaluation of the effectiveness of the FOCUS ADHD App in monitoring adults with attention-deficit/hyperactivity disorder
Authors: Carvalho Luiz Roberto , Haas Letícia M. , Zeni Gregory , Victor Marcelo M. , Techele Stefania P. , Marrone Castanho Júlia , Meneghetti Coimbra Isabel , de Freitas de Sousa Anthony , Ceretta Nathalia , Garrudo Alia , Grevet Eugenio Horacio , Rohde Luis Augusto
Published: June 2023

Background

The current investigation assessed a) the performance of the FOCUS ADHD mobile health application (App) in increasing pharmacological treatment adherence and improving patients’ knowledge of attention-deficit/hyperactivity disorder (ADHD) and b) the impact of implementing a financial incentive for using the App (i.e., a discount on medication).

Methods

In a randomized, blind, parallel-group clinical trial, 73 adults diagnosed with ADHD were allocated into three groups for 3 months: a) Pharmacological treatment as usual (TAU); b) TAU and the App (App Group); and c) TAU and the App + a commercial discount on the purchase of medication prescribed for ADHD treatment (App + Discount Group).

Results

There was no significant difference in mean treatment adherence between groups, assessed as a medication possession ratio (MPR). However, the App + Discount Group exhibited greater medication intake registrations compared with the App Group during the initial phase of the trial. The financial discount also produced a 100% App adoption rate. App use did not increase ADHD knowledge, though knowledge scores were high at baseline. The usability and quality of the App were rated favorably.

Conclusions

The FOCUS ADHD App achieved a high adoption rate and positive evaluations by users. Use of the App did not increase adherence to treatment as measured by MPR, but, for App users, the addition of a financial incentive to use the App produced an increase in treatment adherence in terms of medication intake registrations. The present results offer encouraging data for combining incentives with mobile digital health solutions to positively impact treatment adherence in ADHD.
Clinical Validation of Plasma-Based Genotyping for RAS and BRAF V600E Mutation in Metastatic Colorectal Cancer: SCRUM-Japan GOZILA Substudy
Authors: Aoki Yu , Nakamura Yoshiaki , Denda Tadamichi , Ohta Takashi , Esaki Taito , Shiozawa Manabu , Yamaguchi Kensei , Yamazaki Kentaro , Sunakawa Yu , Kato Takeshi , Okano Naohiro , Taniguchi Hiroya , Sato Taro , Oki Eiji , Nishina Tomohiro , Komatsu Yoshito , Matsuhashi Nobuhisa , Goto Masahiro , Yasui Hisateru , Ohtsubo Koushiro , Moriwaki Toshikazu , Takahashi Naoki , Horita Yosuke , Boku Shogen , Wakabayashi Masashi , Ikeno Takashi , Mitani Ryuta , Yuasa Mihoko , Yoshino Takayuki
Published: June 2023

PURPOSE

Circulating tumor DNA (ctDNA) genotyping on the basis of next-generation sequencing (NGS) may guide targeted therapy for metastatic colorectal cancer (mCRC). However, the validity of NGS-based ctDNA genotyping for RAS/BRAF V600E mutation assessment and the efficacy of anti-EGFR and BRAF-targeted therapies on the basis of ctDNA results remains unclear.

PATIENTS AND METHODS

The performance of NGS-based ctDNA genotyping for RAS/BRAF V600E mutation assessment was compared with that of a validated polymerase chain reaction–based tissue testing in patients with mCRC enrolled in the GOZILA study, a nationwide plasma genotyping study. The primary end points were concordance rate, sensitivity, and specificity. The efficacy of anti-EGFR and BRAF-targeted therapies on the basis of ctDNA were also evaluated.

RESULTS

In 212 eligible patients, the concordance rate, sensitivity, and specificity were 92.9% (95% CI, 88.6 to 96.0), 88.7% (95% CI, 81.1 to 94.0), and 97.2% (95% CI, 92.0 to 99.4) for RAS and 96.2% (95% CI, 92.7 to 98.4), 88.0% (95% CI, 68.8 to 97.5), and 97.3% (95% CI, 93.9 to 99.1) for BRAF V600E, respectively. In patients with a ctDNA fraction of ≥1.0%, sensitivity rose to 97.5% (95% CI, 91.2 to 99.7) and 100% (95% CI, 80.5 to 100.0) for RAS and BRAF V600E mutations, respectively. In addition to a low ctDNA fraction, previous chemotherapy, lung and peritoneal metastases, and interval between dates of tissue and blood collection were associated with discordance. The progression-free survival of anti-EGFR therapy and BRAF-targeted treatment was 12.9 months (95% CI, 8.1 to 18.5) and 3.7 (95% CI, 1.3 to not evaluated) months, respectively, for matched patients with RAS/BRAF V600E results by ctDNA.

CONCLUSION

ctDNA genotyping effectively detected RAS/BRAF mutations, especially with sufficient ctDNA shedding. Clinical outcomes support ctDNA genotyping for determining the use of anti-EGFR and BRAF-targeted therapies in patients with mCRC.
Neurologic Manifestations of Gastrointestinal and Nutritional Disorders
Authors: Diesing T. Scott
Published: June 2023

OBJECTIVE

A tie between nutritional or gastrointestinal and neurologic disease has been recognized for centuries. Many gastrointestinal disorders are associated with neurologic disease through nutritional, immune-mediated, or degenerative pathophysiologies. This article reviews neurologic disorders in patients with gastrointestinal disease and gastrointestinal manifestations in their own neurologic patients.

LATEST DEVELOPMENTS

Development of new gastric and bariatric surgical procedures and the widespread use of over-the-counter gastric acid–reducing medications continue to create vitamin and nutritional deficiencies despite modern diet and supplementation. Some supplements, such as vitamin A, vitamin B6, and selenium, themselves are now found to cause disease. Recent work has shown extraintestinal and neurologic manifestations of inflammatory bowel disease. Chronic brain damage in liver disease has been recognized, and the opportunity to intervene may exist in the covert beginning stages. The characterization of gluten-related neurologic symptoms and differentiation from those of celiac disease is an evolving body of work.

ESSENTIAL POINTS

Gastrointestinal and neurologic diseases related to common immune-mediated, degenerative, or infectious mechanisms are common and can coexist in the same patient. Furthermore, gastrointestinal disease may cause neurologic complications because of nutritional inadequacies, malabsorption, and hepatic dysfunction. In many cases, the complications are treatable but have subtle or protean presentations. Therefore, the consulting neurologist must be current in knowledge of the growing ties between gastrointestinal and neurologic disease.
Neurologic Manifestations of Rheumatologic Disease
Authors: Toledano Michel
Published: June 2023

Objective

This article describes the neurologic manifestations of systemic rheumatologic disorders.

Latest Developments

Although most have historically been classified as autoimmune disorders, rheumatologic diseases are increasingly conceptualized as distributed along a spectrum with various contributions of autoimmune (adaptive immune dysregulation) and autoinflammatory (innate immune dysregulation) mechanisms. Our evolving understanding of systemic immune-mediated disorders has been accompanied by an expansion in our differential diagnoses and therapeutic options.

Essential Points

Rheumatologic disease involves both autoimmune and autoinflammatory mechanisms. Neurologic symptoms can be the first manifestation of these disorders, and familiarity with the systemic manifestations of specific diseases is essential to establish the correct diagnosis. Conversely, knowledge of the neurologic syndromes that are most likely to be associated with specific systemic disorders can help narrow the differential and increase confidence when attributing a neuropsychiatric symptom to an underlying systemic disorder.
Neurologic Complications of COVID-19
Authors: Gill Christine , Cho Tracey A.
Published: June 2023

OBJECTIVE

This article describes the spectrum of neurologic complications occurring in acute or postacute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as the neurologic risks and benefits of vaccination against SARS-CoV-2.

LATEST DEVELOPMENTS

Early in the COVID-19 pandemic, reports of neurologic complications of COVID-19 began to surface. A variety of neurologic conditions have since been reported in association with COVID-19. Understanding of the underlying mechanism of COVID-19 neurologic involvement continues to evolve; however, the evidence seems to suggest that aberrant inflammatory responses may play a role. In addition to neurologic symptoms in acute COVID-19, neurologic post–COVID-19 conditions are increasingly recognized. The development of COVID-19 vaccines has been essential in preventing the spread of COVID-19. With increasing numbers of vaccine doses administered, various neurologic adverse events have been reported.

ESSENTIAL POINTS

Neurologists must be aware of the potential acute, postacute, and vaccine-associated neurologic complications associated with COVID-19 and be poised to serve as integral members of multidisciplinary care teams for patients with COVID-19–related conditions.
Neurologic Complications of Cardiac and Pulmonary Disease
Authors: Mainali Shraddha
Published: June 2023

OBJECTIVE

The heart and lungs work as a functional unit through a complex interplay. The cardiorespiratory system is responsible for the delivery of oxygen and energy substrates to the brain. Therefore, diseases of the heart and lungs can lead to various neurologic illnesses. This article reviews various cardiac and pulmonary pathologies that can lead to neurologic injury and discusses the relevant pathophysiologic mechanisms.

LATEST DEVELOPMENTS

We have lived through unprecedented times over the past 3 years with the emergence and rapid spread of the COVID-19 pandemic. Given the effects of COVID-19 on the lungs and heart, an increased incidence of hypoxic-ischemic brain injury and stroke associated with cardiorespiratory pathologies has been observed. Newer evidence has questioned the benefit of induced hypothermia in patients with out-of-hospital cardiac arrest. Further, global collaborative initiatives such as the Curing Coma Campaign are underway with the goal of improving the care of patients with coma and disorders of consciousness, including those resulting from cardiac and pulmonary pathologies.

ESSENTIAL POINTS

The neurologic complications of cardiorespiratory disorders are common and present in various forms such as stroke or hypoxic and anoxic injury related to cardiac or respiratory failure. With the emergence of the COVID-19 pandemic, neurologic complications have increased in recent years. Given the intimate and interdependent dynamics of the heart, lungs, and brain, it is crucial for neurologists to be aware of the interplay between these organs.
“The Coast Is Not Kenya”:Mwambaoin a “Moment of Danger” in Lamu
Authors: Mahajan Nidhi
Published: June 2023

This article examines the multiple, diverse renderings of the past that came to the fore in the Indian Ocean port city of Lamu at the groundbreaking of the Lamu Port, South Sudan, Ethiopia Transport and Economic Development Corridor (LAPSSET) project in 2012. This infrastructural project includes a megaport and a freight corridor that would make Lamu the Indian Ocean terminus for a rail-land bridge. In Lamu, the LAPSSET project produced anxieties and questions about the past, where different historical narratives—of belonging, sovereignty, and autochthony—bubbled up to the surface. Focusing on two groups in Lamu and the wider Swahili coast, the first a coalition of civil society organizations called Save Lamu and second, the Mombasa Republican Council, a secessionist group, this essay examines the resurgence of older modes of coastal nationalism or mwambao. This article argues that coastal nationalism enshrined notions of Indian Ocean belonging, where the “nation” was defined by the coast's history in the larger Indian Ocean rather than the Kenyan nation-state. These Indian Ocean imaginaries were at the center of cleavages between state and society when construction for LAPSSET began in 2012, gesturing to how sovereignty remains unsettled in coastal East Africa.
Experience of caries and tooth loss in rural citrus workers in Northeast Brazil
Authors: Alvim-Pereira Fabiano , Menezes Vanessa Nascimento , Lima Ricardo Barbosa , Rocha Daniel Maranha da , Da Rocha Milena Cerqueira , De Mendonça Adriano Augusto Melo
Published: June 2023

Objective: To evaluate the experience of caries and tooth loss in rural citrus workers in Northeast Brazil. Methods: This was a cross-sectional, quantitative, and descriptive study carried out using a non-probabilistic sample of rural citrus workers linked to the Occupational Health Reference Center. Generalist and dental questionnaires were applied and clinical examinations were performed by two calibrated examiners on 619 participants in Basic Health Units to establish the sample DMFT index and to detail their characteristics of interest. Results: The sample was predominantly male (71%), with young adults between 20 and 40 years (50,9%), with low education (76%) and low income (59,3%). The mean DMFT index of the sample was 14.29 and the component regarding tooth loss (M) 9.97, corresponding to approximately 70% of this value. Moreover, 90,1% of the evaluated participants had losses of at least one dental element and 27,8% had a functional loss with less than 21 teeth in the oral cavity, while 86.3% said they had never attended an oral health service. Of the participants who have already attended, 83,6% were over six months ago, motivated by pain (43,8%) and caries (14,7%). Conclusions: The rural citrus workers evaluated had negative experiences with dental caries and a high rate of functional tooth loss, leading them vulnerable to stomatognathic system imbalances and showing the need for prevention and promotion of oral health.
As repercussões da gravidez no cotidiano de uma mulher
Authors: Benevides Fernanda Teixeira , Lima Maria Raquel da Silva , Nogueira Maria Dinara de Araújo , Nogueira Valéria Cristina , Maia Carla Soraya Costa , Carvalho Francisco Herlânio Costa
Published: June 2023

Objetivo: Descrever as repercussões da gravidez no cotidiano de uma mulher. Métodos: Estudo exploratório-descritivo com abordagem qualitativa. Foram entrevistadas 25 gestantes entre 20 e 24 semanas de gestação, atendidas em uma instituição na cidade de Fortaleza (CE). A coleta de dados foi por meio de entrevistas semiestruturadas, submetidas à técnica de análise de conteúdo. Foram criadas nuvens de palavras para as categorias, utilizando-se o software NVivo 11. Resultados: A análise comparativa constante permitiu a construção de duas categorias: “impacto da gravidez nas atividades diárias” e “peso corporal da gestação na moda feminina”. A primeira categoria demonstrou o impacto do aumento do tamanho corporal da gestante diante das atividades comuns do dia a dia, a dificuldade para realizar certas atividades, a sobrecarga das articulações e o cansaço relacionado ao aumento do volume corporal na gestação. Os resultados da segunda categoria mostraram que as mudanças gestacionais impactam nas escolhas de vestimenta das mulheres, sendo relatadas as dificuldades para aquisição de um novo vestuário durante esta fase, a procura por lojas especializadas em moda gestante e o reaproveitamento de peças existentes com necessidade de possíveis ajustes. Conclusão: Neste estudo, possibilitou-se a análise dos sentidos atribuídos às mudanças corporais pelas gestantes e observou-se que as transformações gestacionais repercutem diretamente na realização de atividades cotidianas e nas escolhas de vestimenta de mulheres grávidas, demonstrando inúmeras dificuldades a serem compreendidas e enfrentadas durante este período.
Condições de saúde bucal em pessoas acometidas por Covid-19
Authors: Braga Débora Rosana Alves , Saintrain Maria Vieira de Lima , Rodrigues Débora Mota , Bezerra Carina Bandeira , Martins Maria da Glória Almeida
Published: June 2023

Objetivo: Descrever alterações bucais relatadas por pessoas acometidas pela COVID-19 e identificar a relação dessas manifestações com a forma de apresentação da doença (leve ou grave). Métodos: Estudo transversal, descritivo e analítico. O instrumento versou sobre dados sociodemográficos, hábitos deletérios, forma de acometimento da COVID-19 e alterações bucais em adultos residentes no estado do Ceará. A coleta dos dados foi realizada por questionário on-line com utilização dos Formulários Google® disponibilizado de forma pública. Os dados foram analisados utilizando o software SPSS® versão 24.0 IBM®, sendo calculadas frequências absoluta e relativa das variáveis do estudo e razão de prevalência. A associação entre variáveis foi verificada pelo teste Qui-quadrado, com nível de significância de 5%. Resultados: Do total de 1958 respondentes, 586 relataram acometimento pela COVID-19. Dos afetados pela doença, 566 (96,6%) são da faixa etária entre 18 e 59 anos, 436 (74,4%) mulheres, 304 (51,9%) pós-graduados e 358 (51,1%) casados; 391 (66,7%) habitam com três a cinco pessoas e têm rendimento superior a cinco salários-mínimos [290 (49,5%)]. Predominou a forma leve da COVID-19 [312 (53,2%)], embora tenha havido grande percentual da forma grave [274 (46,8%)]. Do total, 123 que tiveram alterações bucais, como dificuldade para mastigar e engolir os alimentos (62;50,4%), queimação na boca (30;24,4%) e ferida na boca (14;11,4%). Os acometidos pela forma grave da COVID-19 mostraram probabilidade 1,55 vezes maior de apresentar alteração bucal quando comparado ao caso leve da doença (p=0,006). Conclusão: Pessoas acometidas com a forma grave da COVID-19 estão mais propensas a apresentar alterações bucais.
Prevalence, causes and impacts of human trafficking in Asian countries: A scoping review
Authors: Khan Zeeshan , Kamaluddin Mohammad Rahim , Meyappan Saravanan , Manap Jamiah , Rajamanickam Ramalinggam
Published: June 2023

Background: In Asian countries, human trafficking is often encountered as forced labor, forced marriage, sex trafficking, men, women, and children exploitation. This review points out how human trafficking activities are prevalent in Asian countries and also reveals different causes that are the basis of increasingly human trafficking in Asian countries such as poverty, unemployment, political uncertainty, war, natural disaster, corruption and weak policies. Human trafficking also creates huge health, physical, psychological and social implications on individuals and the overall society.

Methods: The purpose of this study is to collect evidence on human trafficking in Asian countries. A scoping review methodology was used to systematically search online databases including Sage Journals Online, Wiley Online, Hein Online, Taylor & Francis Online, Web of Science, and Scopus literature to amalgamate information on this issue. For the purposes of this article, 64 studies met the inclusion criteria after searching and screening a total number of 1,278 studies.

Results: The findings of this study were classified under three categories: prevalence of human trafficking in Asia, causes of human trafficking in Asia (poverty and unemployment, environmental and manmade disaster, weak policies and corruption), and impacts of human trafficking including social, health, physical, psychological impacts.

Conclusion: Keeping in mind the prevalence and impacts of human trafficking, the author also recommends some meaningful and practical steps for policymakers and researchers to effectively tackle human trafficking in Asian countries.
Nigella sativa L. seed extracts promote wound healing progress by activating VEGF and PDGF signaling pathways: An in vitro and in silico study
Authors: Palanisamy Chella Perumal , Alugoju Phaniendra , Jayaraman Selvaraj , Poompradub Sirilux
Published: June 2023

Background: A significant area of clinical research is the development of natural wound healing products and the management of chronic wounds. Healing wounds with medicinal plants has been a practice of ancient civilizations for centuries. Nigella sativa L (N. sativa) is a medicinal plant that has several pharmacological properties.

Methods: The present study evaluated the wound healing properties of Nigella sativa L. (N. sativa) seed extracts using normal cell lines such as normal human dermal fibroblasts (NHDFs) and human umbilical vein endothelial cells (HUVECs). The expression levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) were analyzed through western blot analysis. Furthermore, computational analyses were carried out to screen the potential bioactive compounds for wound healing applications.

Results: The results of the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay revealed that, all the tested solvent extracts of N. sativa seeds (including ethanol, ethyl acetate, chloroform, and petroleum ether) did not exert any cytotoxic effects at the tested concentrations. Furthermore, the western blot analysis showed elevated levels of VEGF and PDGF upon treatment with N. sativa seed extracts. Gas chromatography-mass spectrometry (GC-MS) analysis of N. sativa extracts identified 268 phytocompounds. Molecular docking studies revealed that three phytocompounds of N. sativa extracts, including tricyclo[20.8.0.0(7,16)]triacontane, 1(22),7(16)-diepoxy-, adaphostin and obeticholic acid had strong binding affinity with wound healing-related target proteins, showing docking scores ranging from -5.5 to -10.9 Kcal/mol. These compounds had acceptable Absorption, Distribution, Metabolism, and Excretion (ADME) properties.

Conclusions: Based on these results, N. sativa seed extracts might possess potential wound healing properties owing to the presence of a wide range of bioactive components.
Integrative transcriptomic and proteomic study of Zika viral infection reveals potential mechanisms for oncolytic therapy in neuroblastoma
Authors: Sherwood Matt , Zhou Yilu , Sui Yi , Wang Yihua , Skipp Paul , Kaid Carolini , Gray Juliet , Okamoto Keith , Ewing Rob M.
Published: June 2023

Background: Paediatric neuroblastoma and brain tumours account for a third of all childhood cancer-related mortality. High-risk neuroblastoma is highly aggressive and survival is poor despite intensive multi-modal therapies with significant toxicity. Novel therapies are desperately needed. The Zika virus (ZIKV) is neurotropic and there is growing interest in employing ZIKV as a potential therapy against paediatric nervous system tumours, including neuroblastoma.

Methods: Here, we perform extensive analysis of ZIKV infection studies to identify molecular mechanisms that may govern the oncolytic response in neuroblastoma cells. We summarise the neuroblastoma cell lines and ZIKV strains utilised and re-evaluate the infection data to deduce the susceptibility of neuroblastoma to the ZIKV oncolytic response. Integrating transcriptomics, interaction proteomics, dependency factor and compound datasets we show the involvement of multiple host systems during ZIKV infection.

Results: We identified that most paediatric neuroblastoma cell lines are highly susceptible to ZIKV infection and that the PRVABC59 ZIKV strain is the most promising candidate for neuroblastoma oncolytic virotherapy. ZIKV induces TNF signalling, lipid metabolism, the Unfolded Protein Response (UPR), and downregulates cell cycle and DNA replication processes. ZIKV is dependent on sterol regulatory element binding protein (SREBP)-regulated lipid metabolism and three protein complexes; V-ATPase, ER Membrane Protein Complex (EMC) and mammalian translocon. We propose ZIKV non-structural protein 4B (NS4B) as a likely mediator of ZIKVs interaction with IRE1-mediated UPR, lipid metabolism and mammalian translocon.

Conclusions: Our work provides a significant understanding of ZIKV infection in neuroblastoma cells, which will facilitate the progression of ZIKV-based oncolytic virotherapy through pre-clinical research and clinical trials.
Pharmacokinetic and pharmacodynamic profiling of compounds similar to paracetamol from zinc database: an in silico analysis
Authors: Kamakia Faith , Ouma Stephen , Kagia Richard
Published: June 2023

Introduction: Paracetamol is the most used drug for the management of pain and as an antipyretic through its mechanism of action on Cox 1,2 and 3 receptors. Paracetamol is a lipid-soluble molecule that can pass through the Blood Brain Barrier. Paracetamol has been formulated differently to ensure the optimal onset and duration of action as both analgesic and as antipyretic. Paracetamol overdose is associated with major side effects such as liver damage through its metabolite N-acetyl-p-benzoquinone Imine.

Methods: This study generated zinc compounds that are similar in structure to Paracetamol through Ligand-based virtual screening. Molecular docking of these compounds to Cox 1, 2, and 3 receptors followed through Structure-based virtual screening. Compounds with better docking scores to these receptors were analyzed for pharmacokinetics and toxicity profiles.

Results: ZINC01714506; 0.986; ZINC01714507; 0.986; and ZINC00394165; 0.987 showed the highest docking scores to cox 3 receptor with probability scores of -6.7kcal/mol, -6.4 and -6.2 kcal/ mol as compared to Paracetamol with -5.3kcal/mol. ZINC01714507; 0.986; ZINC01714506; 0.986; and ZINC00394165; 0.987; showed higher docking scores to Cox 2 with docking scores of -8.3kcal.mol, -8.1kcal/mole and -8.0 kcal/mol compared to paracetamol with -6.6kcal/mol. ZINC00394165; 0.987; ZINC00406627; 0.980; and ZINC01714506; 0.986; showed highest docking scores to Cox-1 than paracetamol  with scores of -7.7kcal/mol, -7.6 and-7.6kcal/mol. ZINC01714506; 0.986 was predicted the safest with oral LD50 of 2000mg/kg as compared to paracetamol’s 338mg/kg. ZINC00294715; 0.980, ZINC01747085; 0.985, ZINC00394165; 0.987, ZINC00406627; 0.980, ZINC01557001; 0.987 and ZINC19281575; 0.992 were predicted hepatoactive. ZINC00294715; 0.980; ZINC01557001; 0.987; and ZINC19281575; 0.992; lack Blood Brain Barrier permeation. All compounds showed high GIT absorption and all conform to Lipinski’s rule of five.

Conclusion: ZINC01557001; 0.987; ZINC01714506; 0.986; ZINC34120167; 0.994; ZINC00394165; 0.987, ZINC01714507; 0.986; and ZINC01747085; 0.985; are promising in drug discovery for new analgesic and antipyretic drugs, based on better docking scores and better oral LD50
ROLES DE PARTICIPACIÓN Y COMUNICACION EN LA INVESTIGACIÓN EN MATEMÁTICA EDUCATIVA. ¿CUÁLES SERÁN LOS ACUERDOS DE LA COMUNIDAD LATINOAMERICANA?
Authors: Montiel-Espinosa Gisela
Published: June 2023

Cuando se haga pública esta editorial, la Relime habrá iniciado la migración de su contenido al Open Journal Systems –el famoso OJS– y con ello también la actualización de algunas directrices respecto a las Normas y Políticas Editoriales. Una de éstas se refiere al área que el Comité de Ética de Publicaciones (COPE por las siglas en inglés de Committee On Publication Ethics), a partir de su primer reporte en 2003, consideró de las más confusas: la autoría.Han pasado veinte años y el reporte aún se discute para precisar dichas normas y políticas, por lo que se hizo prioritario el construir espacios de difusión y formación, promoviendo una cultura académica que lo integrara en la investigación propia.
IDONEIDAD DIDÁCTICA DE VÍDEOS EDUCATIVOS DE MATEMÁTICAS: UNA EXPERIENCIA CON ESTUDIANTES PARA MAESTRO
Authors: Burgos María , Castillo María José
Published: June 2023

En este trabajo se describe el diseño, implementación y resultados de una acción formativa con 61 estudiantes para maestro de educación primaria, orientada al desarrollo de la competencia de análisis de la idoneidad didáctica de vídeos educativos sobre porcentajes. El análisis a priori del vídeo reveló carencias importantes en las distintas facetas de la idoneidad didáctica, siendo especialmente relevante aquellas detectadas en la dimensión epistémica. La mayoría de los estudiantes para maestro realizaron valoraciones globales pertinentes de la idoneidad didáctica (un 70.49% la consideraron entre baja y media) basando su juicio en el grado de cumplimiento de los indicadores de idoneidad en los distintas componentes. Sin embargo, aunque las sugerencias de mejora indicadas son oportunas, no todos los estudiantes que identifican carencias en los vídeos pueden formular explícitamente cambios al recurso.
Long-Range Social Influence in Phone Communication Networks on Offline Adoption Decisions
Authors: Leng Yan , Dong Xiaowen , Moro Esteban , Pentland Alex
Published: June 2023

We use high-resolution mobile phone data with geolocation information and propose a novel technical framework to study how social influence propagates within a phone communication network and affects the offline decision to attend a performance event. Our fine-grained data are based on the universe of phone calls made in a European country between January and July 2016. We isolate social influence from observed and latent homophily by taking advantage of the rich spatial-temporal information and the social interactions available from the longitudinal behavioral data. We find that influence stemming from phone communication is significant and persists up to four degrees of separation in the communication network. Building on this finding, we introduce a new “influence” centrality measure that captures the empirical pattern of influence decay over successive connections. A validation test shows that the average influence centrality of the adopters at the beginning of each observational period can strongly predict the number of eventual adopters and has a stronger predictive power than other prevailing centrality measures. Our centrality measure can be used to improve optimal seeding strategies in contexts with influence over phone calls, such as targeted or viral marketing campaigns.
Formação, docência e autoria: pensando o ensino-aprendizagem de história – Entrevista com Ilmar Rohloff de Mattos
Authors: Silva Daniel Pinha , Rangel Marcelo De Mello
Published: June 2023

Entrevista. Revista Maracanan, PPGH/UERJ, Rio de Janeiro, n. 32 - Dossiê "Teoria da história, ensino de história e universidade: diálogos e perspectivas", p. 16-35, jan.-abr. 2023.
‘Into the fire’: a focus group study of redeployed staff during the COVID-19 pandemic
Authors: Green Laura , Murphy Fiona , Davies Alice
Published: June 2023

Background:

During the COVID-19 pandemic, redeployed staff whose services were temporarily suspended were offered a range of opportunities for work to support efforts to manage the impact of the pandemic. A new team, known as the Cygnets was established within an existing team SWAN, to provide non-specialist end of life and bereavement care during the COVID-19 pandemic. It is important to evaluate new services and one important component of this is understanding the perceptions of those staff who took on the new role.

Aim:

To evaluate the service from the perspectives of staff.

Method:

A purposive sample of 14 NHS staff who had worked as Cygnets during the COVID-19 pandemic took part in three focus groups.

Results:

The themes identified broadly followed the focus group schedule. Participants considered that overall, they had benefited greatly from the challenge of taking on the Cygnet role, and that this had been a learning experience.

Conclusions:

This was a rapid response to a need for increased provision of compassionate end-of-life care and was a beneficial experience for staff. More research is required into the broader value of the role within the hospital infrastructure.
An Analysis of Grammar Textbook at the Preparatory Year
Authors: Mohammad Taj , Khan Soada Idris
Published: June 2023

Textbooks are of utmost importance in an academic setting. They cannot achieve their goals and objectives until they address the particular needs of students. The current study aims to assess the grammar textbook used at Najran University's Preparatory Year Program. The study's objectives are to examine the textbook's material in light of the course objectives and to pinpoint the factors that contribute to discrepancies between course objectives and learning outcomes. Additionally, it offers solutions to close the gaps between the course objectives and learning objectives. Twenty PYP teachers were chosen to participate in the study. To collect information from the participants, a quantitative questionnaire with 10 statements based on the course objectives was used. The teachers were also the subject of a qualitative interview to get their advice and insights. The analysis backs the current textbook because of its advantages, which the teachers who participated in the questionnaire said they liked. However, there is always room to update the textbook and improve particular sections or courses to better suit the needs of students. This specific section replacement can address those precise goals that the questionnaire's respondents did not rate very high.
The Impact of Adults' Used Skills on Their Self-Evaluated Skills and Social Lives Over Time
Authors: Wolgast Anett
Published: June 2023

Previous research focused on individuals’ background, contexts and cognitive performance in education, work, and life. Given the increasing number of people living alone temporarily, the question arises whether the frequent use of skills, including social skills, relates to individuals’ later positively self-evaluated skills and social lives. Based on an integrated framework, the current analysis aimed to disentangle these relationships with longitudinal data from Germany over three years. The target sample consisted of n = 3263 working adults. A Bayesian structural equation model included adults’ frequent use of skills, self-evaluated skills, household size, close friends, and seven covariates (e.g., numeracy and literacy test scores, weekly working hours. The results suggested positive relationships between adults’ frequent use of numeracy, literacy, and social skills and later self-evaluations (except literacy used on self-evaluated numeracy). Those who less frequently used social skills three years earlier were also less likely to have a larger household size than those who reporting frequently using their social skills. Adults who frequently used literacy skills three years earlier reported higher numbers of close friends than those who less frequently used literacy. The findings highlight the importance of adults’ social skills and frequently used skills for self-evaluated numeracy and literacy.
Rural poverty and labour force participation: Evidence from Indonesia’s Village fund program
Authors: Rammohan Anu , Tohari Achmad
Published: June 2023

Rural residents account for the bulk of poverty in developing countries. This paper evaluates the impact of Indonesia’s Dana Desa program (Village Fund Program or VFP) on rural poverty and female labour force participation. The VFP, introduced in 2014, was an ambitious national-level village governance program which transferred administrative responsibility and financial resources to Indonesia’s 79,000 plus rural villages, providing them with the autonomy to invest in rural infrastructure, human capital, and job creation programs. Using nationally representative data from before and after the program, we show that the implementation of the VFP was associated with an improvement in rural household’s consumption expenditure among households, particularly among agricultural households. Female labour force participation in rural areas increased by about 10 percentage points and there is also evidence of a sectoral shift away from agricultural employment towards jobs in the service sector. This improvement in labour force participation is associated with poverty reduction among rural households.
Reputation based on internal capabilities: The case of small enterprises within the Colombian orange economy
Authors: Cuero-Acosta Yonni Angel , Amado-Mateus Marelby , Ricardo Torralba Barreto Daniel , Castiblanco-Moreno Suelen Emilia
Published: June 2023

This study seeks to understand how micro, small, and medium-sized enterprises (MSMEs) can be innovative while developing their reputation. In doing so, this study focuses on companies classified as promoters of Colombia’s “orange economy,” which relates to the country’s cultural and creative diversity. Firms with a non-technological emphasis also require knowledge, innovation, and reputation to perform better. In this regard, the study is based on the work of Hormiga and Garcia-Almeida (2016) who proposed the relationship between accumulated knowledge and innovation as background of reputation. In this paper, the purpose is to understand the internal reputation-building process carried out by MSMEs and the variables that intervene. Therefore, this research accounts for how MSMEs can build their reputation through innovation and accumulated knowledge. For this, a survey was conducted in 320 orange economy MSMEs located in Bogotá, Colombia, and the relationship of these variables was statistically tested through a quantitative analysis of multivariate data. Innovation was found to not impact the performance of companies, but this can be associated to factors that were not considered in this research. However, it is proposed to refine the original model by considering the manager’s perspective. It is recommended that entrepreneurs invest resources in accumulating internal (tacit) knowledge to improve skills that enhance reputation.
Cellular apoptosis and cell cycle arrest as potential therapeutic targets for eugenol derivatives in Candida auris
Authors: Alam Hammad , Srivastava Vartika , Sekgele Windy , Wani Mohmmad Younus , Al-Bogami Abdullah Saad , Molepo Julitha , Ahmad Aijaz
Published: June 2023

Candida auris, the youngest Candida species, is known to cause candidiasis and candidemia in humans and has been related to several hospital outbreaks. Moreover, Candida auris infections are largely resistant to the antifungal drugs currently in clinical use, necessitating the development of novel medications and approaches to treat such infections. Following up on our previous studies that demonstrated eugenol tosylate congeners (ETCs) to have antifungal activity, several ETCs (C1-C6) were synthesized to find a lead molecule with the requisite antifungal activity against C. auris. Preliminary tests, including broth microdilution and the MUSE cell viability assay, identified C5 as the most active derivative, with a MIC value of 0.98 g/mL against all strains tested. Cell count and viability assays further validated the fungicidal activity of C5. Apoptotic indicators, such as phosphatidylserine externalization, DNA fragmentation, mitochondrial depolarization, decreased cytochrome c and oxidase activity and cell death confirmed that C5 caused apoptosis in C. auris isolates. The low cytotoxicity of C5 further confirmed the safety of using this derivative in future studies. To support the conclusions drawn in this investigation, additional in vivo experiments demonstrating the antifungal activity of this lead compound in animal models will be needed.
Biological expressions of early life trauma in the immune system of older adults
Authors: Noppert Grace A. , Duchowny Kate A. , Stebbins Rebecca , Aiello Allison E. , Dowd Jennifer B. , Clarke Philippa
Published: June 2023

Background

Poor immune function is associated with increased risk for a number of age-related diseases, however, little is known about the impact of early life trauma on immune function in late-life.

Methods

Using nationally representative data from the Health and Retirement Study (n = 5,823), we examined the association between experiencing parental/caregiver death or separation before age 16 and four indicators of immune function in late-life: C-reactive Protein (CRP), Interleukin-6 (IL-6), soluble Tumor Necrosis Factor (sTNFR), and Immunoglobulin G (IgG) response to cytomegalovirus (CMV). We also examined racial/ethnic differences.

Findings

Individuals that identified as racial/ethnic minorities were more likely to experience parental/caregiver loss and parental separation in early life compared to Non-Hispanic Whites, and had poorer immune function in late-life. We found consistent associations between experiencing parental/caregiver loss and separation and poor immune function measured by CMV IgG levels and IL-6 across all racial/ethnic subgroups. For example, among Non-Hispanic Blacks, those that experienced parental/caregiver death before age 16 had a 26% increase in CMV IgG antibodies in late-life (β = 1.26; 95% CI: 1.17, 1.34) compared to a 3% increase in CMV antibodies among Non-Hispanic Whites (β = 1.03; 95% CI: 0.99, 1.07) controlling for age, gender, and parental education.

Interpretation

Our results suggest a durable association between experiencing early life trauma and immune health in late-life, and that structural forces may shape the ways in which these relationships unfold over the life course.