bluuebunny/crossref_metadata_2025 huggingface dataset:
Formulation of Cinnamon (Cinnamomum verum) oil loaded solid lipid nanoparticles and evaluation of its antibacterial activity against Multi-drug Resistant Escherichia coli
Authors: Nemattalab Mehran , Rohani Masoumeh , Evazalipour Mehdi , Hesari Zahra
Published: November 2022

Today, the increment in microbial resistance has guided the researches focus into new antimicrobial compounds or transmission systems. Escherichia coli (E. coli) is an opportunistic pathogen, producing a biofilm responsible for a wide range of nosocomial infections which are often difficult to eradicate with available antibiotics. On the other hand, Cinnamomum verum (cinnamon oil) (CO) is widely used as a natural antibacterial agent and Solid lipid nanoparticles (SLNs) are promising carriers for antibacterial compounds due to their lipophilic nature and ease of transmission through the bacterial cell wall. In this study, nanoparticles containing cinnamon oil (CO-SLN) were prepared by dual emulsion method and evaluated in terms of particle size, shape, entrapment efficiency (EE), transmission electron microscopy (TEM), oil release kinetics, and cell compatibility. The antibacterial activity of CO-SLN and CO against 10 drug-resistant E. coli strains was investigated. The anti-biofilm activity of CO-SLN on the selected pathogen was also investigated. Nanoparticles with an average size of 337.6 nm, and zeta potential of -26.6 mV were fabricated and their round shape was confirmed by TEM images. The antibacterial effects of CO-SLN and CO were reported with MIC Value of 60–75 µg/mL and 155–165 µg/mL and MBC value of 220–235 µg/ml and 540–560 µg/ml, respectively. On the other hand, CO-SLN with 1/2 MIC concentration had the greatest inhibition of biofilm formation in 24 h of incubation (55.25%). The data presented indicate that the MIC of CO-SLN has significantly reduced and it seems that SLN has facilitated and promoted CO transmission through the cell membrane.
A scoping review of the literature on the impact of the COVID-19 quarantine on the psychological wellbeing of medical students
Authors: Vythilingam Divya I. , Prakash Amog , Nourianpour Milad , Atiomo William U.
Published: November 2022

Background

The goal of this study was to identify the nature and extent of the available published research on the impact of social isolation, on the psychological wellbeing of medical students, who had to quarantine due to the COVID-19 pandemic.

Methods

Design. Scoping review. Search strategy. The PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews), guideline, was used to structure this study. A search strategy was carried out across six bibliographic databases. PubMed, Embase, ERIC, Scopus, Cochrane Database of Systematic Reviews and Web of Science. The following search terms were used, “medical student*” AND “impact” AND “quarantine” AND “COVID-19”. Searches were initially confined to articles published (excluding conference abstracts) between 1 January 2019- 21 August 2021 but updated in September 2022 with the original search terms expanded to include “isolation” or “lockdown” as well as “quarantine” and the period of search extended to 21 August 2022. A search of secondary references was conducted. Data from the selected studies were extracted, and the following variables recorded; first author and year of publication, country of study, study design, sample size, participants, mode of analysing impact of quarantine from COVID-19 on mental health and results of the studies.

Results

A total of 223 articles were identified in the original search in 2021 and 387 articles, in the updated search in 2022. Following the exclusion of duplicates and application of the agreed inclusion and exclusion criteria, 31 full-text articles were identified for the final review, most of which were cross sectional studies. Sample sizes ranged from 13 to 4193 students and most studies used a variety of self-administered questionnaires to measure psychological wellbeing. Overall, 26 of the 31 articles showed that quarantine had a negative impact on the psychological well-being of medical students. However, two studies showed no impact, and three studies showed an improvement.

Conclusion

The evidence is growing. Quarantine because of the COVID-19 pandemic may have had a negative impact on the psychological wellbeing of medical students, but this is not certain. There is therefore a need for more studies to further evaluate this research question.
Feasibility and acceptability of e-learning to upskill diabetes educators in supporting people experiencing diabetes distress: a pilot randomised controlled trial
Authors: Halliday Jennifer A. , Russell-Green Sienna , Hagger Virginia , O Eric , Morris Ann , Sturt Jackie , Speight Jane , Hendrieckx Christel
Published: November 2022

Background

Diabetes distress is a commonly experienced negative emotional response to the ongoing burden of diabetes. Holistic diabetes care, including attention to diabetes distress, is recommended in clinical guidelines, yet not routinely implemented. Diabetes health professionals have highlighted lack of training as a barrier to implementation of psychological care. Therefore, we developed an e-learning: ‘Diabetes distress e-learning: A course for diabetes educators’ to address this need. This pilot study aimed to examine the feasibility of evaluating the e-learning in a randomised controlled trial study, the acceptability of the e-learning to credentialled diabetes educators (CDEs); and preliminary evidence of its effect upon CDEs’ diabetes distress-related knowledge, motivation, confidence, behavioural skills, and barriers to implementation.

Methods

A pilot, unblinded, 2-armed, parallel group randomised controlled trial. Participants were recruited during a 4-month timeframe. Eligible participants were CDEs for ≥ 1 year providing care to ≥ 10 adults with type 1 or type 2 diabetes per week. Participants were randomly allocated (1:1 computer automated) to 1 of 2 learning activities: diabetes distress e-learning (intervention) or diabetes distress chapter (active control). They had 4 weeks to access the activity. They completed online surveys at baseline, 2-week and 12-week follow-up.

Results

Seventy-four eligible CDEs (36 intervention, 38 active control) participated. At baseline, recognition of the clinical importance of diabetes distress was high but knowledge and confidence to provide support were low-to-moderate. Engagement with learning activities was high (intervention: 83%; active control: 92%). Fifty-five percent returned at least 1 follow-up survey. All 30 intervention participants who returned the 2-week follow-up survey deemed the e-learning high quality and relevant. Systemic barriers (e.g., financial limitations and access to mental health professionals) to supporting people with diabetes distress were common at baseline and follow-up. 

Conclusions

The e-learning was acceptable to CDEs. The study design was feasible but needs modification to improve follow-up survey return. The e-learning showed potential for improving diabetes distress-related knowledge, confidence and asking behaviours, but systemic barriers to implementation remained. Systemic barriers need to be addressed to facilitate implementation of support for diabetes distress in clinical practice. Future larger-scale evaluation of the e-learning is warranted.
Pride and adversity among nurses and physicians during the pandemic in two US healthcare systems: a mixed methods analysis
Authors: Burstyn Igor , Holt Karyn
Published: November 2022

Background

Our aims were to examine themes of the most difficult or distressing events reported by healthcare workers during the first wave of COVID-19 pandemic in two US health care systems in order to identify common themes and then to relate them to both behavioral theory and measures of anxiety and depression.

Methods

We conducted a cross-sectional survey of nurses and physicians during the early phases of the COVID-19 pandemic in the US. An emailed recruitment letter was sent, with about half choosing to supply open-ended responses relevant to thematic analysis. We measured symptoms of anxiety and depression separately, captured demographics, and asked two open-ended questions regarding events that were the most difficult or stressful, and reinforced pride. We reported descriptive statistics and coded thematic categories for their continuum “pride” and “distress” the factors related to fostering well-being according to the Self-Determination Theory.

Results

Themes that emerged from these narratives were congruent with prediction of Self-Determination theory that autonomy-supportive experiences will foster pride, while autonomy-thwarting experiences will cause distress. Those who reported distressful events were more anxious and depressed compared to those who did not. Among those who reported incidences that reinforced pride in the profession, depression was rarer compared to those who did not. These trends were evident after allowing for medical history and other covariates in logistic regressions.

Conclusion

Causal claims from our analysis should be made with caution due to the cross-sectional research design. Understanding perceptions of the pandemic by nurses and physicians may help identify and manage sources of distress, and suggest means of mitigating the risk of mental health distress through autonomy-supportive policies.
An integrated in silico-in vitro approach for identifying therapeutic targets against osteoarthritis
Authors: Lesage Raphaëlle , Ferrao Blanco Mauricio N. , Narcisi Roberto , Welting Tim , van Osch Gerjo J. V. M. , Geris Liesbet
Published: November 2022

Background

Without the availability of disease-modifying drugs, there is an unmet therapeutic need for osteoarthritic patients. During osteoarthritis, the homeostasis of articular chondrocytes is dysregulated and a phenotypical transition called hypertrophy occurs, leading to cartilage degeneration. Targeting this phenotypic transition has emerged as a potential therapeutic strategy. Chondrocyte phenotype maintenance and switch are controlled by an intricate network of intracellular factors, each influenced by a myriad of feedback mechanisms, making it challenging to intuitively predict treatment outcomes, while in silico modeling can help unravel that complexity. In this study, we aim to develop a virtual articular chondrocyte to guide experiments in order to rationalize the identification of potential drug targets via screening of combination therapies through computational modeling and simulations.

Results

We developed a signal transduction network model using knowledge-based and data-driven (machine learning) modeling technologies. The in silico high-throughput screening of (pairwise) perturbations operated with that network model highlighted conditions potentially affecting the hypertrophic switch. A selection of promising combinations was further tested in a murine cell line and primary human chondrocytes, which notably highlighted a previously unreported synergistic effect between the protein kinase A and the fibroblast growth factor receptor 1.

Conclusions

Here, we provide a virtual articular chondrocyte in the form of a signal transduction interactive knowledge base and of an executable computational model. Our in silico-in vitro strategy opens new routes for developing osteoarthritis targeting therapies by refining the early stages of drug target discovery.

Graphical Abstract
Molecular, cellular and neurological consequences of infection by the neglected human pathogen Nocardia
Authors: Ji Xingzhao , Han Lichao , Zhang Weiying , Sun Lina , Xu Shuai , Qiu Xiaotong , Fan Shihong , Li Zhenjun
Published: November 2022

Background

Nocardia is a facultative intracellular pathogen that infects the lungs and brains of immunocompromised patients with consequences that can be fatal. The incidence of such infections is rising, immunocompetent individuals are also being infected, and there is a need to learn more about this neglected bacterial pathogen and the interaction with its human host.

Results

We have applied dual RNA-seq to assess the global transcriptome changes that occur simultaneously in Nocardia farcinica (N. farcinica) and infected human epithelial alveolar host cells, and have tested a series of mutants in this in vitro system to identify candidate determinants of virulence. Using a mouse model, we revealed the profiles of inflammation-related factors in the lung after intranasal infection and confirmed that nbtB and nbtS are key virulence genes for Nocardia infection in vivo. Regarding the host response to infection, we found that the expression of many histones was dysregulated during the infection of lung cells, indicating that epigenetic modification might play a crucial role in the host during Nocardia infection. In our mouse model, Nocardia infection led to neurological symptoms and we found that 15 of 22 Nocardia clinical strains tested could cause obvious PD-like symptoms. Further experiments indicated that Nocardia infection could activate microglia and drive M1 microglial polarization, promote iNOS and CXCL-10 production, and cause neuroinflammation in the substantia nigra, all of which may be involved in causing PD-like symptoms. Importantly, the deletion of nbtS in N. farcinica completely attenuated the neurological symptoms.

Conclusions

Our data contribute to an in-depth understanding of the characteristics of both the host and Nocardia during infection and provide valuable clues for future studies of this neglected human pathogen, especially those addressing the underlying causes of infection-related neurological symptoms.
Molecular testing to deliver personalized chemotherapy recommendations: risking over and undertreatment
Authors: Olivier Timothée , Prasad Vinay
Published: November 2022

Background

In the adjuvant setting of cancer treatment, de-escalation strategies have the goal of omitting or minimizing treatment in patients, without compromising outcomes. Historically, eligibility for adjuvant treatment solely relied on the patient’s clinical and tumor’s pathological characteristics. At the turn of the century, based on new biological understanding, molecular-based strategies were tested and sometimes implemented.

Main body

However, we illustrate how molecularly based de-escalation strategies may paradoxically lead to overtreatment. This may happen when the novel approach is tested in lieu of standard management and may not yield the same results when being implemented in addition to usual practice. In the DYNAMIC trial, adjuvant chemotherapy decision in stage II colon cancer was compared between a circulating tumor DNA (ctDNA)-based approach and the standard care. We show this may result in more patients receiving oxaliplatin-based chemotherapy and may expose a similar proportion of patients to chemotherapy if the novel strategy is implemented in addition to usual practice. The other potential risk is undertreatment. We provide an illustration of early breast cancer, where the decision of adjuvant chemotherapy based on the gene expression signature MammaPrint may lead to inferior outcomes as compared with the clinico-pathologic strategy. This may also happen when non-inferiority designs have large margins. Among solutions, it should be acknowledged that clinico-pathological features, like T4 in colon cancer, may not be abandoned and replaced by novel strategies in real-life practice. Therefore, novel strategies should be tested in addition to standard of care, and not in lieu of. Second, de-escalation trials should focus on the settings where the standard of care has a widespread agreement. This would avoid the risk of testing non-inferiority against an ineffective therapy, which guarantees successes without providing informative data.

Conclusion

Simply because a molecular test is rational does not mean it can improve patient outcomes. Here, we highlight how molecular test-based strategies may result in either overtreatment or undertreatment. In the rapidly evolving field of medicine, where technological advances may be transformative, our piece highlights scientific pitfalls to be aware of when considering running such trials or before implementing novel strategies in daily practice.
The transfer of maternal antibodies and dynamics of maternal and natural infection-induced antibodies against coxsackievirus A16 in Chinese children 0–13 years of age: a longitudinal cohort study
Authors: Zhou Jiaxin , Zhou Yonghong , Luo Kaiwei , Liao Qiaohong , Zheng Wen , Gong Hui , Shi Huilin , Zhao Shanlu , Wang Kai , Qiu Qi , Dai Bingbing , Ren Lingshuang , Wang Lili , Gao Lidong , Xu Meng , Liu Nuolan , Lu Wanying , Zheng Nan , Chen Xinhua , Chen Zhiyuan , Yang Juan , Cauchemez Simon , Yu Hongjie
Published: November 2022

Background

A major hand-foot-and-mouth disease (HFMD) pathogen, coxsackievirus A16 (CVA16), has predominated in several of the last 10 years and caused the largest number of HFMD outbreaks between 2011 and 2018 in China. We evaluated the efficacy of maternal anti-CVA16 antibody transfer via the placenta and explored the dynamics of maternal and natural infection-induced neutralizing antibodies in children.

Methods

Two population-based longitudinal cohorts in southern China were studied during 2013–2018. Participants were enrolled in autumn 2013, including 2475 children aged 1–9 years old and 1066 mother-neonate pairs, and followed for 3 years. Blood/cord samples were collected for CVA16-neutralizing antibody detection. The maternal antibody transfer efficacy, age-specific seroprevalence, geometric mean titre (GMT) and immune response kinetics were estimated.

Results

The average maternal antibody transfer ratio was 0.88 (95% CI 0.80–0.96). Transferred maternal antibody levels declined rapidly (half-life: 2.0 months, 95% CI 1.9–2.2 months). The GMT decayed below the positive threshold (8) by 1.5 months of age. Due to natural infections, it increased above 8 after 1.4 years and reached 32 by 5 years of age, thereafter dropping slightly. Although the average duration of maternal antibody-mediated protection was < 3 months, the duration extended to 6 months on average for mothers with titres ≥ 64.

Conclusions

Anti-CVA16 maternal antibodies are efficiently transferred to neonates, but their levels decline quickly. Children aged 0–5 years are the main susceptible population and should be protected by CVA16 vaccination, with the optimal vaccination time between 1.5 months and 1 year of age.
Transcriptome analysis of intestine from alk-SMase knockout mice reveals the effect of alk-SMase
Authors: Zhu Jiang , Wang Lingqi , Guo Zhongwu , Zhang Tao , Zhang Ping
Published: November 2022

Objective

Intestinal alkaline sphingomyelinase (alk-SMase) generates ceramide and inactivates platelet-activating factor associated with digestion and inhibition of cancer. There is few study to analyze the correlated function and characterize the genes related to alk-SMase comprehensively. We characterised transcriptome landscapes of intestine tissues from alk-SMase knockout (KO) mice aiming to identify novel associated genes and research targets.

Methods

We performed the high-resolution RNA sequencing of alk-SMase KO mice and compared them to wild type (WT) mice. Differentially expressed genes (DEGs) for the training group were screened. Functional enrichment analysis of the DEGs between KO mice and WT mice was implemented using the Database for Annotation, Visualization and Integrated Discovery (DAVID). An integrated protein–protein interaction (PPI) and Kyoto Encyclopedia of Genes and Genomes (KEGG) network was chose to study the relationship of differentially expressed gene. Moreover, quantitative real-time polymerase chain reaction (qPCR) was further used to validate the accuracy of RNA-seq technology.

Results

Our RNA-seq data found 97 differentially expressed mRNAs between the WT mice and alk-SMase gene NPP7 KO mice, in which 32 were significantly up-regulated and 65 were down-regulated, including protein coding genes, non-coding RNAs. Notably, the results of gene ontology functional enrichment analysis indicated that DEGs were functionally associated with the immune response, regulation of cell proliferation and development related terms. Additionally, an integrated network analysis was shown that some modules was significantly related to alk-SMase and with accordance of previously results. We chose 6 of these genes randomly were validated the accuracy of RNA-seq technology using qPCR and 2 genes showed difference significantly (P < 0.05).

Conclusions

We investigated the potential biological significant of alk-SMase with high resolution genome-wide transcriptome of alk-SMase knockout mice. The results revealed new insight into the functional modules related to alk-SMase was involved in the intestinal related diseases.
Defining the impact of platelet-to-lymphocyte ratio on patient survival with gastric neuroendocrine neoplasm: a retrospective cohort analysis
Authors: Liang Wenquan , Xu Xinxin , Liu Yuhua , Cui Jianxin , Gao Yunhe , Wang Chuang , Zhuang Ziwei , Zhang Kecheng , Xi Hongqing , Cai Aizhen , Wei Bo , Chen Lin
Published: November 2022

Background

Gastric neuroendocrine neoplasm (g-NEN) is a rare but heterogeneous neoplasm, with an increasing incidence yearly. Conventional prognostic markers of g-NEN remain limited which could only be detected after surgery. There is an urgent need to explore new prognostic markers for g-NEN patients. This study aimed to investigate the prognostic value of platelet-to-lymphocyte, ratio (PLR) and the association between PLR and body mass index (BMI) in patients with gastric neuroendocrine neoplasms (g-NEN).

Methods

A retrospective cohort of patients with g-NEN from January 2001 through June 2016 was examined. The prognostic significance of PLR was determined by multiple regression analysis in different models. Stratified analysis was performed to examine the prognostic value of PLR at different BMI levels.

Results

In total, 238 patients were enrolled. Those with higher PLRs tended to undergo open surgery, had larger tumor sizes, were diagnosed more frequently with neuroendocrine carcinoma, and had higher tumor grades. PLR was significantly associated with the survival of patients with g-NEN. With PLR increased per standard deviation, the all-cause mortality risk of patients with g-NEN increased by 67%, 63%, and 54% in the crude (HR = 1.67, 95% CI 1.32–2.12, P < 0.001), minimally adjusted (HR = 1.63, 95% CI 1.28–2.08, P < 0.001), and fully adjusted (HR = 1.54, 95% CI 1.202–1.98, P = 0.001) models, respectively. Patients with higher PLR (quartile 4, ≥ 187) had a 1.8-fold increase in all-cause mortality risk compared with those with lower PLR (quartile 1–3, < 187). Furthermore, there was a significant interaction effect between BMI subgroups and PLR in predicting the survival of patients with g-NEN (PLR regarded as a continuous variable: all P for interaction < 0.05 in the crude, minimally adjusted, and fully adjusted models; PLR regarded as a categorical variable: P for interaction < 0.05 in the fully adjusted model). Patients with g-NEN with the characteristics of higher PLR (quartile 4, ≥ 187) and non-obesity (BMI < 25 kg/m2) had worse survival than others (P < 0.05).

Conclusion

The inflammation marker PLR has an independent prognostic value for patients with g-NENs, and high PLR combined with non-obesity increases the mortality risk of these patients.
Factors predicting admission of psychiatric emergency contacts after presenting to the emergency department: results of a regression analysis
Authors: Kirchner Heribert , Schaefer Martin , Ullrich Heiko , Hulsmans Nik , Juckel Georg , Brzoska Patrick , Pajonk Frank-Gerald Bernhard
Published: November 2022

Background

Psychiatric emergency patients have great relevance in the interdisciplinary emergency department. Emergency physicians in this setting often have to make decisions under time pressure based on incomplete information regarding the patient’s further treatment. The aim of this study was to identify possible predictors associated with an increased likelihood of inpatient psychiatric admission.

Methods

A retrospective cross-sectional study of all psychiatric emergency contacts in an interdisciplinary emergency department (ED) of a general hospital in a large German city was conducted for 2015. A binary regression analysis was performed to identify possible predictors.

Results

In 2015, a total of 21421 patient contacts were reported in the emergency department, of which 1733 were psychiatric emergencies. Psychiatric emergency was the fourth most common cause presenting to the ED. The most common diagnosis given was mental and behavioral disorders due to the use of psychotropic substances (F1). Factors associated with an increased probability of inpatient psychiatric admission were previously known patients, patients under a legal care order (guardianship), and previous outpatient medical contact. No association for gender or age was found. Data demonstrated a negative relationship between a neurotic, stress-related and somatoform disorder diagnosis and admission.

Conclusions

The present study shows some significant characteristics associated with an increased likelihood of emergency admission. Independent of the health care system, the predictors found seem to be relevant with regard to the probability of admission, when compared internationally. To improve the treatment of patients in emergency units, these factors should be taken into account.
The severity of moral distress in nurses: a systematic review and meta-analysis
Authors: Salari Nader , Shohaimi Shamarina , Khaledi-Paveh Behnam , Kazeminia Mohsen , Bazrafshan Mohammad-Rafi , Mohammadi Masoud
Published: November 2022

Background

Moral distress is one of the most important problems that nurses face in their care of patients. Various studies have reported the frequency and severity of moral distress in nurses. However, to date, a comprehensive study that shows the results of these research across the world was not found, therefore due to the importance of this issue, its role in the health of nurses and patients, and the lack of general statistics about it worldwide, the present study was conducted to determine the frequency and severity of moral distress in nurses through a systematic review and meta-analysis.

Methods

In this review study, searching national and international databases of SID, MagIran, IranMedex, IranDoc, Google Scholar, Embase, ScienceDirect, Scopus, CINHAL, PubMed, and Web of Science (WoS) between 2005 and February 2020 were extracted. The random-effects model was used for analysis, and the heterogeneity of studies with the I2 index was investigated. Data were analyzed using Comprehensive Meta-Analysis (Version 2).

Results

The frequency of moral distress in 9 articles with a sample size of 1576 persons was 1.7 ± 0.5 from (0–4), in 13 articles with a sample size of 1870 persons, 3.07 ± 0.1 from (0–5), in 6 articles with a sample size of 1316 persons, 3.2 ± 0.29 from (0–6), in 18 articles with a sample size of 1959 persons, 4.6 ± 0.518 from (1–7) and in 35 articles with a sample size of 3718 persons, 81.1 ± 4.6 from (216–30), and the severity of moral distress in 4 articles with a sample size of 1116 persons, 1.7 ± 0.37 from (0–4), in 5 articles with a sample size of 1282 persons, 2.6 ± 0.28 from (0–5), in 5 articles with a sample size of 944 persons, 3.9 ± 0.63 from (0–6) and in 8 articles with a sample size of 901 persons was 82.3 ± 5.4 (0–216).

Conclusion

The results of this study showed that the frequency and severity of moral distress in nurses are high and are a serious problem in nurses. Therefore, policymakers in this field should consider its role in the health of nurses and patients.
Conflict, epidemic and faith communities: church-state relations during the fight against Covid-19 in north-eastern DR Congo
Authors: Kangamina Sadiki , Falisse Jean-Benoit , Baba Amuda , Grant Liz , Pearson Nigel , Way Yossa , Wild-Wood Emma
Published: November 2022

Background

Understanding and improving access to essential services in (post)-conflict settings requires paying particular attention to the actors who occupy the space left ‘empty’ by weak or deficient State institutions. Religious institutions often play a fundamental role among these actors and typically benefit from high trust capital, a rare resource in so-called ‘fragile’ states. While there is a literature looking at the role faith organisations play to mobilise and sensitise communities during emergencies, our focus is on a different dimension: the reconfiguration of the relationship between religion and health authorities impelled by health crises.

Methods

We analyse observations, interviews, and focus group discussions with 21 leaders from eight different religious groups in Ituri province in 2020–2021.

Results

Faith institutions handled the Covid-19 lockdown period by using and redeploying structures at the grassroots level but also by responding to health authorities’ call for support. New actors usually not associated with the health system, such as revivalist churches, became involved. The interviewed religious leaders, especially those whose congregations were not previously involved in healthcare provision, felt that they were doing a favour to the State and the health authorities by engaging in community-level awareness-raising, but also, crucially, by ‘depoliticising’ Covid-19 through their public commitment against Covid-19 and work with the authorities in a context where the public response to epidemics has been highly contentious in recent years (particularly during the Ebola outbreak). The closure of places of worship during the lockdown shocked all faith leaders but, ultimately, most were inclined to follow and support health authorities. Such experience was, however, often one of frustration and of feeling unheard.

Conclusion

In the short run, depoliticization may help address health emergencies, but in the longer run and in the absence of a credible space for discussion, it may affect the constructive criticism of health system responses and health system strengthening. The faith leaders are putting forward the desire for a relationship that is not just subordination of the religious to the imperatives of health care but a dialogue that allows the experiences of the faithful in conflict zones to be brought to the fore.
Characterization of an Entner–Doudoroff pathway-activated Escherichia coli
Authors: Kim Ye Eun , Cho Kyung Hyun , Bang Ina , Kim Chang Hee , Ryu Young Shin , Kim Yuchan , Choi Eun Mi , Nong Linh Khanh , Kim Donghyuk , Lee Sung Kuk
Published: November 2022

Background

Escherichia coli have both the Embden–Meyerhof–Parnas pathway (EMPP) and Entner–Doudoroff pathway (EDP) for glucose breakdown, while the EDP primarily remains inactive for glucose metabolism. However, EDP is a more favorable route than EMPP for the production of certain products.

Results

EDP was activated by deleting the pfkAB genes in conjunction with subsequent adaptive laboratory evolution (ALE). The evolved strains acquired mutations in transcriptional regulatory genes for glycolytic process (crp, galR, and gntR) and in glycolysis-related genes (gnd, ptsG, and talB). The genotypic, transcriptomic and phenotypic analyses of those mutations deepen our understanding of their beneficial effects on cellulosic biomass bio-conversion. On top of these scientific understandings, we further engineered the strain to produce higher level of lycopene and 3-hydroxypropionic acid.

Conclusions

These results indicate that the E. coli strain has innate capability to use EDP in lieu of EMPP for glucose metabolism, and this versatility can be harnessed to further engineer E. coli for specific biotechnological applications.
Factors associated with the periodicity of Loa loa microfilaremia in the Republic of the Congo
Authors: Campillo Jérémy T. , Louya Frédéric , Bikita Paul , Missamou François , Pion Sébastien D. S. , Boussinesq Michel , Chesnais Cédric B.
Published: November 2022

Background

Loa loa microfilariae circulate in the peripheral blood of human hosts following a diurnal periodicity, with maximal microfilaremia levels generally observed between 10:00 am and 3:00 pm. Few studies have assessed factors potentially associated with this periodicity.

Methods

Microfilaremia data were collected repeatedly between 9:00 am and 8:00 pm from 13 individuals in the Republic of the Congo. Using local polynomial regression (LOESS), we determined the best models representing the dynamics of microfilaremia over this period. In a second step, using cosinor models, we evaluated the influence of sex, age, and body temperature on the periodicity of L. loa microfilaremia in blood.

Results

All subjects reached their maximum microfilaremia between 10:00 am and 4:00 pm. Individual microfilaremia showed different patterns between individuals, and some clearly showed multiple peaks within a day. LOESS provided a good fit to the observed data. Without adjustment, the maximum microfilarial density was reached around 11:00 am. Adjustment revealed three distinct modes of microfilaremia, occurring around 10:00 am, 1:00 pm, and 4:00 pm. Cosinor models also provided good fit to our data. After adjustment on body temperature, the L. loa microfilaremia fluctuation amplitude decreased significantly from 1684.8 to 310.6 microfilariae(mf)/ml and the predicted peak was estimated at 12:02 pm.

Conclusions

We characterized the periodicity of L. loa microfilaremia mathematically with two different approaches: cosinor models and LOESS regression. Both models suggest that body temperature plays a role in the variation in microfilaremia within a day. Further studies are needed to identify individual co-factors affecting microfilaremia.

Graphical Abstract
Anti-leucine-rich glioma-inactivated 1 encephalitis: two case reports and a review of the literature
Authors: Karvigh Sanaz Ahmadi , Salehizadeh Saeideh , Vahabizad Fahimeh
Published: November 2022

Background

Anti-leucine-rich glioma-inactivated 1 encephalitis is a newly emerged entity characterized by frequent faciobrachial dystonic seizures and a wide spectrum of subacute clinical symptoms such as other seizure types, mood and behavioral changes, and memory loss. We should be aware of differentiating this diagnosis from psychogenic nonepileptic seizures. Mesial temporal, limbic structures, and basal ganglia are the most commonly involved regions.

Case presentation

Here we review the available data, and report on two young Iranian (White) females, 24 and 18 years old, who represent distinct aspects of the disease. The clinical presentation and degree of tissue involvement varies to some extent in the two reported cases. Case 1 had prominent neuropsychiatric symptoms and suffered from frequent faciobrachial dystonic seizures with more significant basal ganglia involvement, whereas case 2 suffered from severe memory decline and dialeptic seizures along with mesial temporal involvement. Symptoms were refractory to usual treatment and prompt immunotherapy was needed.

Conclusions

This disease has a rather favorable outcome provided that treatment is initiated early. However, resistance to first-line treatment, relapses, and long-term complications highlight the need to establish reliable biomarkers to distinguish different subtypes of this disorder to predict the clinical outcome and prognosis, and to refine management.
Afrormosin exerts an anticancer effect via MAPK and AKT signaling pathways in B16F10 cells
Authors: Kim Huiji , Han Minjoo , Shin Seong-Ah , An Jangeun , Ahn Mi-Jeong , Lee Jun Hyuck , Park Hyun Ho , Lee Chang Sup
Published: November 2022

Melanoma is a deadly skin cancer with high mortality, and its incidence is increasing every year. Although numerous anticancer drugs have been developed, these treatments have various side effects, such as skin rash, fatigue, diarrhea, cough, and muscle pain. Therefore, there is a need for research on novel anticancer drugs with low cytotoxicity and few side effects. In this study, we investigated whether afrormosin (7-hydroxy-4′,6-dimethoxyisoflavone), a member of the isoflavonoid family, could have the potential as a novel anticancer drug. Afrormosin decreased the viability of B16F10 melanoma cells in a time- and dose-dependent manner. We also found that the afrormosin-induced decrease in cell viability was caused by the reduction of cell proliferation through Go/G1 arrest and the induction of apoptosis in B16F10 melanoma cells. Furthermore, afrormosin decreased the metastatic activity (cell invasion and migration) of B16F10 melanoma cells. At the molecular level, afrormosin reduced the levels of Bcl-2, an anti-apoptotic protein, and augmented the levels of Bax, a pro-apoptotic protein, and p53, a tumor suppressor. Additionally, procaspase-3 levels were reduced by afrormosin treatment. When we examined the signaling pathways affected by afrormosin, we found that the AKT/ERK pathways were inhibited and the p38/JNK pathway was activated by afrormosin. Collectively, these results suggest the potential anticancer effect of afrormosin, making it a prospective candidate for development as an anticancer drug.
Dysregulation of neuroprotective astrocytes, a spectrum of microglial activation states, and altered hippocampal neurogenesis are revealed by single-cell RNA sequencing in prion disease
Authors: Slota Jessy A. , Sajesh Babu V. , Frost Kathy F. , Medina Sarah J. , Booth Stephanie A.
Published: November 2022

Prion diseases are neurodegenerative disorders with long asymptomatic incubation periods, followed by a rapid progression of cognitive and functional decline culminating in death. The complexity of intercellular interactions in the brain is challenging to unravel and the basis of disease pathobiology remains poorly understood. In this study, we employed single cell RNA sequencing (scRNAseq) to produce an atlas of 147,536 single cell transcriptomes from cortex and hippocampus of mice infected with prions and showing clinical signs. We identified transcriptionally distinct populations and sub-populations of all the major brain cell-types. Disease-related transcription was highly specific to not only overarching cell-types, but also to sub-populations of glia and neurons. Most striking was an apparent decrease in relative frequency of astrocytes expressing genes that are required for brain homeostasis such as lipid synthesis, glutamate clearance, synaptic modulation and regulation of blood flow. Additionally, we described a spectrum of microglial activation states that suggest delineation of phagocytic and neuroinflammatory functions in different cell subsets. Differential responses of immature and mature neuron populations were also observed, alongside abnormal hippocampal neurogenesis. Our scRNAseq library provides a new layer of knowledge on single cell gene expression in prion disease, and is a basis for a more detailed understanding of cellular interplay that leads to neurodegeneration.
Diffuse Large B-Cell Lymphoma in Chile: The Impact of Combined CHOP Plus Rituximab in the Public Health System
Authors: Cabrera María Elena , Peña Camila , Leon Pilar , Lois Vivianne , Rojas Hernán , Vega Valeska , Pizarro Alvaro , Calderon Susana , Rojas Christine , Aspillaga Augusto , Gonzalez M. Luisa , Intriago Marvila , Rojas Bernardita , Hales Cecilia , Oliva Jacqueline , Romero Mónica , Capurro Marisa , Castillo Jorge J.
Published: November 2022

PURPOSE

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype. The purpose of this study was to evaluate the clinical features, prognostic factors, and results of DLBCL that was treated in the cancer centers of the public health system in Chile and compare cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

PATIENTS AND METHODS

Patients age > 15 years who were treated in 18 cancer centers in the country between 2001 and 2017 were included. The Kaplan-Meier method was used to calculate overall survival (OS), and Cox proportional hazard regression modeling was used to evaluate the effect of the addition of rituximab to CHOP on OS.

RESULTS

A total of 1,807 patients were evaluated. The median age at diagnosis was 62 (range, 15-95) years, with a female predominance (53%). Half of the patients were age ≥ 60 years. Serology for HIV infection was positive in 5% of cases (96 cases). International Prognostic Index scores were available for 90% of patients, of which 45% had low-risk, 25% low-intermediate-risk, 18% high-intermediate-risk, and 11% high-risk scores. CHOP was administered to 986 patients (55%; median follow-up, 13.2 years) and R-CHOP to 821 patients (45%; median follow-up, 8.4 years). R-CHOP was associated with superior OS compared with CHOP (5-year 66% v 48%, and 10-year 53% v 35%; P < .001).

CONCLUSION

Rituximab improved the survival of patients with DLBCL diagnosed and treated in Chile. The benefit was sustained over time, with curative rates of > 50%. This intervention shows that the inclusion of this biological drug justified the expenses incurred by the Ministry of Health in the National Lymphoma Protocols in Chile.
Resistance Mechanisms to Anti–Epidermal Growth Factor Receptor Therapy in RAS/RAF Wild-Type Colorectal Cancer Vary by Regimen and Line of Therapy
Authors: Parseghian Christine M. , Sun Ryan , Woods Melanie , Napolitano Stefania , Lee Hey Min , Alshenaifi Jumanah , Willis Jason , Nunez Shakayla , Raghav Kanwal P. , Morris Van K. , Shen John P. , Eluri Madhulika , Sorokin Alexey , Kanikarla Preeti , Vilar Eduardo , Rehn Marko , Ang Agnes , Troiani Teresa , Kopetz Scott
Published: November 2022

PURPOSE

Acquired resistance to anti–epidermal growth factor receptor (EGFR) inhibitor (EGFRi) therapy in colorectal cancer (CRC) has previously been explained by the model of acquiring new mutations in KRAS/NRAS/EGFR, among other MAPK-pathway members. However, this was primarily on the basis of single-agent EGFRi trials and little is known about the resistance mechanisms of EGFRi combined with effective cytotoxic chemotherapy in previously untreated patients.

METHODS

We analyzed paired plasma samples from patients with RAS/BRAF/EGFR wild-type metastatic CRC enrolled in three large randomized trials evaluating EGFRi in the first line in combination with chemotherapy and as a single agent in third line. The mutational signature of the alterations acquired with therapy was evaluated. CRC cell lines with resistance to cetuximab, infusional fluorouracil, leucovorin, and oxaliplatin, and SN38 were developed, and transcriptional changes profiled.

RESULTS

Patients whose tumors were treated with and responded to EGFRi alone were more likely to develop acquired mutations (46%) compared with those treated in combination with cytotoxic chemotherapy (9%). Furthermore, contrary to the generally accepted hypothesis of the clonal evolution of acquired resistance, we demonstrate that baseline resistant subclonal mutations rarely expanded to become clonal at progression, and most remained subclonal or disappeared. Consistent with this clinical finding, preclinical models with acquired resistance to either cetuximab or chemotherapy were cross-resistant to the alternate agents, with transcriptomic profiles consistent with epithelial-to-mesenchymal transition. By contrast, commonly acquired resistance alterations in the MAPK pathway do not affect sensitivity to cytotoxic chemotherapy.

CONCLUSION

These findings support a model of resistance whereby transcriptomic mechanisms of resistance predominate in the presence of active cytotoxic chemotherapy combined with EGFRi, with a greater predominance of acquired MAPK mutations after single-agent EGFRi. The proposed model has implications for prospective studies evaluating EGFRi rechallenge strategies guided by acquired MAPK mutations, and highlights the need to address transcriptional mechanisms of resistance.
COVID-19 Vaccine–Related Beliefs and Behaviors Among Patients With and Survivors of Hematologic Malignancies
Authors: Akesson Jesper , Weiss Elisa S. , Sae-Hau Maria , Gracia Gabriela , Lee Marialanna , Culp Lucy , Connell Brian , Butterfield Steve , Conti Rena M.
Published: November 2022

PURPOSE:

Patients with and survivors of hematologic malignancies are particularly vulnerable to COVID-19 disease and complications. This study examined patients' vaccination attitudes and behaviors and their correlates.

METHODS:

A two-wave survey was fielded in December 2020 and June 2021 among hematologic malignancy patients and survivors (N = 2,272). Demographic characteristics, intent to get vaccinated, vaccination status, attitudes toward vaccination, and level of trust in specific sources of information about COVID-19 vaccines were assessed. Descriptive statistics were calculated, and linear probability models were estimated to examine binary outcomes and their correlates.

RESULTS:

In December 2020, before COVID-19 vaccines were available, 73% stated they were likely or very likely to get vaccinated if an FDA-approved vaccine became available; however, in June 2021 over 90% reported being vaccinated. Being younger, unmarried, trusting local faith leaders, and not having a bachelor's degree or more were negatively associated with getting vaccinated. Among those hesitant in December 2020, those who expressed a distrust of vaccines in general were least likely to get vaccinated. Being vaccinated in June 2021 was positively associated with the degree to which respondents trust their oncologist, federal agencies, and pharmaceutical companies. Oncologists and primary care physicians were reported as the most trusted sources for information about vaccines.

DISCUSSION:

COVID-19 vaccine hesitancy remains a public policy concern even now, as additional boosters are recommended among vulnerable populations. Our findings suggest that patient trust in their treating physicians can play a critical role in promoting individual patient and public health goals.
Patients With Serious Mental Illness Can Engage in Tobacco Treatment Trials and Tobacco Cessation Interventions During Cancer Treatment
Authors: Steffens Eleanor B. , Park Elyse R. , Muzikansky Alona , Streck Joanna M. , Ostroff Jamie S. , Rasmussen Autumn W. , Ponzani Colin , Perez Giselle K. , Regan Susan , Rigotti Nancy A. , Irwin Kelly E.
Published: November 2022

PURPOSE:

More than half of individuals with serious mental illness (SMI) smoke, contributing to premature cancer mortality. A cancer diagnosis provides an opportunity to assist with smoking cessation; however, supportive oncology trials frequently exclude patients with SMI. To fill this gap, we examined differences in engagement and tobacco cessation in a pragmatic clinical trial.

METHODS:

We recruited 303 participants from two National Cancer Institute–designated Comprehensive Cancer Centers, of which 10% had prior diagnoses of SMI (major depressive disorder, bipolar disorder, and schizophrenia spectrum disorders). We compared self-reported smoking behaviors, patient attitudes and beliefs about cessation, and rates of trial completion, engagement, and smoking abstinence among recently diagnosed patients with cancer with and without SMI. Six months after trial completion, we completed qualitative interviews on barriers and facilitators to tobacco cessation in a random sample of participants with SMI.

RESULTS:

Trial participants with SMI had similar motivation to quit smoking as those without SMI. Additionally, participants with SMI had a similar ability to engage in a tobacco treatment trial (6.5 counseling sessions completed v 7.3 sessions) and benefit from tobacco treatment as those without SMI (32.3% v 27.8% 6-month quit rates).

CONCLUSION:

Patients with cancer and SMI were able to engage in and benefit from a tobacco cessation trial integrated into cancer care. A cancer diagnosis provides an opportunity to assist patients with SMI with smoking cessation referrals and treatment. Pragmatic supportive oncology trials that include a diverse population of adults with SMI are needed to inform care delivery and improve cancer outcomes for patients with SMI and cancer.