bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the molecular makeup of support cells in insect camera eyes
Authors: Rathore Shubham , Stahl Aaron , Benoit Joshua B. , Buschbeck Elke K.
Published: November 2023

Animals typically have either compound eyes, or camera-type eyes, both of which have evolved repeatedly in the animal kingdom. Both eye types include two important kinds of cells: photoreceptor cells, which can be excited by light, and non-neuronal support cells (SupCs), which provide essential support to photoreceptors. At the molecular level deeply conserved genes that relate to the differentiation of photoreceptor cells have fueled a discussion on whether or not a shared evolutionary origin might be considered for this cell type. In contrast, only a handful of studies, primarily on the compound eyes of Drosophila melanogaster, have demonstrated molecular similarities in SupCs. D. melanogaster SupCs (Semper cells and primary pigment cells) are specialized eye glia that share several molecular similarities with certain vertebrate eye glia, including Müller glia. This led us to question if there could be conserved molecular signatures of SupCs, even in functionally different eyes such as the image-forming larval camera eyes of the sunburst diving beetle Thermonectus marmoratus. To investigate this possibility, we used an in-depth comparative whole-tissue transcriptomics approach. Specifically, we dissected the larval principal camera eyes into SupC- and retina-containing regions and generated the respective transcriptomes. Our analysis revealed several common features of SupCs including enrichment of genes that are important for glial function (e.g. gap junction proteins such as innexin 3), glycogen production (glycogenin), and energy metabolism (glutamine synthetase 1 and 2). To evaluate similarities, we compared our transcriptomes with those of fly (Semper cells) and vertebrate (Müller glia) eye glia as well as respective retinas. T. marmoratus SupCs were found to have distinct genetic overlap with both fly and vertebrate eye glia. These results suggest that T. marmoratus SupCs are a form of glia, and like photoreceptors, may be deeply conserved.
Exploration of key drug target proteins highlighting their related regulatory molecules, functional pathways and drug candidates associated with delirium: evidence from meta-data analyses
Authors: Mosharaf Md Parvez , Alam Khorshed , Gow Jeff , Mahumud Rashidul Alam
Published: November 2023

Background

Delirium is a prevalent neuropsychiatric medical phenomenon that causes serious emergency outcomes, including mortality and morbidity. It also increases the suffering and the economic burden for families and carers. Unfortunately, the pathophysiology of delirium is still unknown, which is a major obstacle to therapeutic development. The modern network-based system biology and multi-omics analysis approach has been widely used to recover the key drug target biomolecules and signaling pathways associated with disease pathophysiology. This study aimed to identify the major drug target hub-proteins associated with delirium, their regulatory molecules with functional pathways, and repurposable drug candidates for delirium treatment.

Methods

We used a comprehensive proteomic seed dataset derived from a systematic literature review and the Comparative Toxicogenomics Database (CTD). An integrated multi-omics network-based bioinformatics approach was utilized in this study. The STRING database was used to construct the protein-protein interaction (PPI) network. The gene set enrichment and signaling pathways analysis, the regulatory transcription factors and microRNAs were conducted using delirium-associated genes. Finally, hub-proteins associated repurposable drugs were retrieved from CMap database.

Results

We have distinguished 11 drug targeted hub-proteins (MAPK1, MAPK3, TP53, JUN, STAT3, SRC, RELA, AKT1, MAPK14, HSP90AA1 and DLG4), 5 transcription factors (FOXC1, GATA2, YY1, TFAP2A and SREBF1) and 6 microRNA (miR-375, miR-17-5, miR-17-5p, miR-106a-5p, miR-125b-5p, and miR-125a-5p) associated with delirium. The functional enrichment and pathway analysis revealed the cytokines, inflammation, postoperative pain, oxidative stress-associated pathways, developmental biology, shigellosis and cellular senescence which are closely connected with delirium development and the hallmarks of aging. The hub-proteins associated computationally identified repurposable drugs were retrieved from database. The predicted drug molecules including aspirin, irbesartan, ephedrine-(racemic), nedocromil, and guanidine were characterized as anti-inflammatory, stimulating the central nervous system, neuroprotective medication based on the existing literatures. The drug molecules may play an important role for therapeutic development against delirium if they are investigated more extensively through clinical trials and various wet lab experiments.

Conclusion

This study could possibly help future research on investigating the delirium-associated therapeutic target biomarker hub-proteins and repurposed drug compounds. These results will also aid understanding of the molecular mechanisms that underlie the pathophysiology of delirium onset and molecular function.
Exploring the efficacy of multi-flavored feature extraction with radiomics and deep features for prostate cancer grading on mpMRI
Authors: Khanfari Hasan , Mehranfar Saeed , Cheki Mohsen , Mohammadi Sadr Mahmoud , Moniri Samir , Heydarheydari Sahel , Rezaeijo Seyed Masoud
Published: November 2023

Background

The purpose of this study is to investigate the use of radiomics and deep features obtained from multiparametric magnetic resonance imaging (mpMRI) for grading prostate cancer. We propose a novel approach called multi-flavored feature extraction or tensor, which combines four mpMRI images using eight different fusion techniques to create 52 images or datasets for each patient. We evaluate the effectiveness of this approach in grading prostate cancer and compare it to traditional methods.

Methods

We used the PROSTATEx-2 dataset consisting of 111 patients’ images from T2W-transverse, T2W-sagittal, DWI, and ADC images. We used eight fusion techniques to merge T2W, DWI, and ADC images, namely Laplacian Pyramid, Ratio of the low-pass pyramid, Discrete Wavelet Transform, Dual-Tree Complex Wavelet Transform, Curvelet Transform, Wavelet Fusion, Weighted Fusion, and Principal Component Analysis. Prostate cancer images were manually segmented, and radiomics features were extracted using the Pyradiomics library in Python. We also used an Autoencoder for deep feature extraction. We used five different feature sets to train the classifiers: all radiomics features, all deep features, radiomics features linked with PCA, deep features linked with PCA, and a combination of radiomics and deep features. We processed the data, including balancing, standardization, PCA, correlation, and Least Absolute Shrinkage and Selection Operator (LASSO) regression. Finally, we used nine classifiers to classify different Gleason grades.

Results

Our results show that the SVM classifier with deep features linked with PCA achieved the most promising results, with an AUC of 0.94 and a balanced accuracy of 0.79. Logistic regression performed best when using only the deep features, with an AUC of 0.93 and balanced accuracy of 0.76. Gaussian Naive Bayes had lower performance compared to other classifiers, while KNN achieved high performance using deep features linked with PCA. Random Forest performed well with the combination of deep features and radiomics features, achieving an AUC of 0.94 and balanced accuracy of 0.76. The Voting classifiers showed higher performance when using only the deep features, with Voting 2 achieving the highest performance, with an AUC of 0.95 and balanced accuracy of 0.78.

Conclusion

Our study concludes that the proposed multi-flavored feature extraction or tensor approach using radiomics and deep features can be an effective method for grading prostate cancer. Our findings suggest that deep features may be more effective than radiomics features alone in accurately classifying prostate cancer.
The impact of covid-19 pandemic on pregnancy outcome
Authors: Gholami Roya , Borumandnia Nasrin , Kalhori Elham , Taheri Mahshid , Khodakarami Nahid
Published: November 2023

Background

The acute respiratory disease caused by the coronavirus (COVID-19) has spread rapidly worldwide yet has not been eliminated. The infection is especially deadly in vulnerable populations. The current studies indicate that pregnant women are at greater risk of getting seriously ill. Even though fetuses protect against disease, the additional finding showed that the COVID-19 pandemic could increase fetal and maternal morbidities. In a situation where COVID-19 and new strains of the virus are still not controlled, scientists predicted that the world might experience another pandemic. Consequently, more research about the effects of COVID-19 infection on pregnancy outcomes is needed. This study aimed to compare the pregnancy outcomes of Iranian pregnant women in the first year of the pandemic with the previous year.

Methods

This prospective cross-sectional study was performed to compare the pregnancy outcome during the COVID-19 pandemic among Iranian pregnant women who gave birth during the pandemic and one year before the pandemic (2019–2020 and 2020–2021). The sample size was 2,371,332 births registered at hospitals and birth centers platforms. The studied variables include stillbirth, congenital anomaly, birth weight, preeclampsia, gestational diabetes, cesarean section, ICU admission, mean of the gestational age at birth, preterm births, NICU admission, neonatal mortality and the percentage of deliveries with at least one complication such as blood transfusion and postpartum ICU admission. Analyzing data was done by using SPSS version 25 software.

Results

We found statistical differences between pregnancy and birth outcomes during the COVID-19 pandemic compared to one year before. The risk of preeclampsia, gestational diabetes, cesarean section, preterm birth and NICU admission were clinically significant. Also, there was a significant decrease in mean gestational age.

Conclusion

The COVID-19 pandemic has affected the pregnancy outcome by increasing morbidities and complications during pregnancy, birth, and postpartum. In addition, extensive quarantine outbreaks disrupted the healthcare system and hindered access to prenatal services. It is necessary to develop preventive and therapeutic care protocols for similar pandemic conditions.
Application of CT and MRI images based on an artificial intelligence algorithm for predicting lymph node metastasis in breast cancer patients: a meta-analysis
Authors: Liu Cheng-Jie , Zhang Lei , Sun Yi , Geng Lei , Wang Rui , Shi Kai-Min , Wan Jin-Xin
Published: November 2023

Background

This study aimed to comprehensively evaluate the accuracy and effect of computed tomography (CT) and magnetic resonance imaging (MRI) based on artificial intelligence (AI) algorithms for predicting lymph node metastasis in breast cancer patients.

Methods

We systematically searched the PubMed, Embase and Cochrane Library databases for literature from inception to June 2023 using keywords that included ‘artificial intelligence’, ‘CT,’ ‘MRI’, ‘breast cancer’ and ‘lymph nodes’. Studies that met the inclusion criteria were screened and their data were extracted for analysis. The main outcome measures included sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and area under the curve (AUC).

Results

A total of 16 studies were included in the final meta-analysis, covering 4,764 breast cancer patients. Among them, 11 studies used the manual algorithm MRI to calculate breast cancer risk, which had a sensitivity of 0.85 (95% confidence interval [CI] 0.79–0.90; p < 0.001; I2 = 75.3%), specificity of 0.81 (95% CI 0.66–0.83; p < 0.001; I2 = 0%), a positive likelihood ratio of 4.6 (95% CI 4.0–4.8), a negative likelihood ratio of 0.18 (95% CI 0.13–0.26) and a diagnostic odds ratio of 25 (95% CI 17–38). Five studies used manual algorithm CT to calculate breast cancer risk, which had a sensitivity of 0.88 (95% CI 0.79–0.94; p < 0.001; I2 = 87.0%), specificity of 0.80 (95% CI 0.69–0.88; p < 0.001; I2 = 91.8%), a positive likelihood ratio of 4.4 (95% CI 2.7–7.0), a negative likelihood ratio of 0.15 (95% CI 0.08–0.27) and a diagnostic odds ratio of 30 (95% CI 12–72). For MRI and CT, the AUC after study pooling was 0.85 (95% CI 0.82–0.88) and 0.91 (95% CI 0.88–0.93), respectively.

Conclusion

Computed tomography and MRI images based on an AI algorithm have good diagnostic accuracy in predicting lymph node metastasis in breast cancer patients and have the potential for clinical application.
Efficacy and safety of first-line combination therapy versus monotherapy for vitreoretinal lymphoma: a systematic review and meta-analysis
Authors: Gao Jing , Peng Xiaoyan , Wang Liang
Published: November 2023

Background

Vitreoretinal lymphoma (VRL) is usually treated with a combination of intraocular methotrexate (ioMTX), high-dose intravenous methotrexate (HD-MTX), or local radiotherapy (RT) as the first options. The effectiveness and safety of monotherapy like bruton’s tyrosine kinase inhibitors (BTKi) for PVRL remain uncertain.

Methods

A systematic review and meta-analysis of clinical trial data and conference abstracts in VRL patients treated with first-line combination therapy or monotherapy were conducted through a search of PubMed, Embase, and Scopus databases until December 2022. A total of 24 studies comprising 517 patients were included, and survival data were extracted from 279 patients due to inconsistent units across studies.

Results

The combined treatment group used ioMTX + chemotherapy (in 4 studies), RT + chemotherapy (in 2 studies), ioMTX/HD-MTX based regimen (in 2 studies), ioMTX + RT + chemotherapy (in 2 studies), ioMTX + lenalidomide/BTKi (in 2 studies) and combination of multiple therapies (in 7 studies). The monotherapy group was mainly treated with oral monotherapies such as BTKi. The combination therapy had a higher overall response rate (ORR) and complete response rate (CRR) than monotherapy (ORR: 96% vs. 72%, CRR: 92% vs. 63%). Combination therapy also resulted in a longer median progression-free survival (28.8 months vs. 13 months, p = 0.012). However, the combination therapy group had more severe side effects (grade 3/4 toxicity) than the monotherapy group (45% vs. 8%).

Conclusion

The study showed combination therapy had better OR and CR rates, longer survival, and more toxicity than monotherapy. While BTK inhibitors were well-tolerated, long-term effectiveness needs confirmation from prospective studies. In addition, given the small number of studies of monotherapy for VRL, more studies are needed to validate its effects.

Trial registration

CRD42023400305.
Bedtime regularity predicts positive affect among veterans with posttraumatic stress disorder: an ecological momentary assessment study
Authors: Song Jiyoung , Fisher Aaron J. , Woodward Steven H.
Published: November 2023

Background

Regularizing bedtime and out-of-bed times is a core component of behavioral treatments for sleep disturbances common among patients with posttraumatic stress disorder (PTSD). Although improvements in subjective sleep complaints often accompany improvements in PTSD symptoms, the underlying mechanism for this relationship remains unclear. Given that night-to-night sleep variability is a predictor of physical and mental well-being, the present study sought to evaluate the effects of bedtime and out-of-bed time variability on daytime affect and explore the optimal window lengths of over which variability is calculated.

Methods

For about 30 days, male U.S. military veterans with PTSD (N = 64) in a residential treatment program provided ecological momentary assessment data on their affect and slept on beds equipped with mattress actigraphy. We computed bedtime and out-of-bed time variability indices with varying windows of days. We then constructed multilevel models to account for the nested structure of our data and evaluate the impact of bedtime and out-of-bed time variability on daytime affect.

Results

More regular bedtime across 6–9 days was associated with greater subsequent positive affect. No similar effects were observed between out-of-bed time variability and affect.

Conclusions

Multiple facets of sleep have been shown to differently predict daily affect, and bedtime regularity might represent one of such indices associated with positive, but not negative, affect. A better understanding of such differential effects of facets of sleep on affect will help further elucidate the complex and intertwined relationship between sleep and psychopathology.

Trial registration

The trial retrospectively was registered on the Defense Technical Information Center website: Award # W81XWH-15–2-0005.
Determine the factors that affected COVID-19 prevention behaviors based on constructs of social cognition theory
Authors: Soltani Raheleh , Shamsi Mohsen , Moradi Atefe
Published: November 2023

Background

COVID-19 is a universal challenge and novel disease is one of the core public health concerns. This study aimed to determine the factors that affected COVID-19 prevention behaviors (CPB) based on constructs of Social Cognition Theory (SCT).

Methods

This cross-sectional study was conducted on 426 participants referred to health centers of Arak from October 2021 to February 2022, and they were selected through a multi-stage random sampling method. Data were collected via a self-administered questionnaire which includes socio-demographic data (6 items), COVID-19 prevention behaviors (12 items), and SCT constructs related to COVID-19 (32 items). SPSS Ver-16 statistical software was used to analyze the data with one-way ANOVA, independent samples t-test, and multiple linear regressions. The significance level of α = 0.05 was considered for all tests.

Results

The mean age was 37.8 years (SD = 12.2) and ranged from 17 to 81. According to the results, 51.2% had higher education and 52.6% of the participants were female. The mean (SD) of COVID-19 preventive behaviors was 43 (SD = 7.8) out of 60. There was statistical association between CPB and three constructs of SCT. Multiple regression showed that the outcomes expectations (β = 0.11, p < 0.001), self-regulation (β = 0.41, p < 0.001), and self-efficacy (β = 0.30, p < 0.001), age, gender, and history of COVID 19infection were associated with CPB and those described 61% of the variance of CPB.

Conclusion

Rendering to the result of this study constructs of SCT is the key predictor of participants’ CPB. Hence, based on these predictors, effective interventions and healthy messages could be designed based on this predictor—outcomes expectations, self-regulation, social support, and self-efficacy which can be beneficial to improve healthy behavior.
The rate of ward to intensive care transfer and its predictors among hospitalized COPD patients, a retrospective study in a local tertiary center in Saudi Arabia
Authors: Naser Abdallah Y , Dairi Mohammad Saleh , Alwafi Hassan , Ashoor Deema Sami , Qadus Sami , Aldhahir Abdulelah M , Alqarni Abdullah A , Elrefaey Wael Aly , Qanash Sultan , Hafiz Waleed , Alqahtani Jaber S. , Ekram Rakan , Abuirmeileh Amjad , Jarab Anan S. , Badr Omaima Ibrahim
Published: November 2023

Objective

To investigate the prevalence of intensive care unit (ICU) admission and its predictors among hospitalized chronic obstructive pulmonary disease (COPD) patients.

Methods

An observational retrospective study was conducted. All patients with a confirmed diagnosis of COPD according to the GOLD guidelines between 28 and 2020 and 1 March 2023 at Al-Noor Specialist Hospital were included in this study. Patients were excluded if a preemptive diagnosis of COPD was made clinically without spirometry evidence of fixed airflow limitation. Descriptive results were presented as frequency (percentage) for categorical variables and mean (SD) for continuous variables and to estimate prevalence of ICU admission. Predictors of ICU admission among hospitalized COPD patients were determined using logistic regression analysis. A SPSS (Statistical Package for the Social Sciences) version 25 was used to perform all statistical analysis.

Results

A total of 705 patients with COPD were included in this study. The mean age was 65.4 (25.3) years. Around 12.4% of the hospitalized patients were admitted to the ICD. Logistic regression analysis identified that older age (OR; 1.92, (1.41–2.62)), smoking (OR; 1.60 (1.17–2.19)), and having specific comorbidities (Hypertension (OR; 1.98 (1.45–2.71)), Diabetes mellitus (OR; 1.42 (1.04–1.93)), GERD (OR; 2.81 (1.99–3.96)), Ischemic heart disease (OR; 3.22 (2.19–4.75)), Obstructive sleep apnea syndrome (OR; 2.14 (1.38–3.33)), stroke (OR; 4.51 (2.20–9.26))) were predictors of ICU admissions among patients with COPD.

Conclusions

Our study found that a step-up approach to inpatient COPD management requires admission to the ICU in 12.4%, for which age, smoking status, cardiovascular, and stroke were important predictors. Further clinical research is needed to provide a validated model that can be incorporated into clinical practice to monitor this patient population during their admission and identify at-risk individuals for early transfer to higher acuity settings and intensive care units.
Virtual clinic for young people with type 1 diabetes: a randomised wait-list controlled study
Authors: Leksell Janeth , Toft Eva , Rosman Jessica , Eriksson Jan W. , Fischier Johan , Lindholm-Olinder Anna , Rosenblad Andreas , Nerpin Elisabet
Published: November 2023

Background

The transition from paediatric to adult care for young adults with type 1 diabetes poses unique challenges. Virtual diabetes clinics using smartphone applications offer a promising approach to support self-management and enhance communication with healthcare providers. The primary objective of this study was to evaluate the effects of a virtual diabetes clinic on glycaemic control, treatment satisfaction, and quality of life among young adults diagnosed with type 1.

Methods

79 participants with type 1 diabetes aged 18–25 years were included in a prospective, single-centre, randomised, wait-list controlled trial. Participants were randomly assigned to either the intervention group or the wait-list control group. The intervention group received instant access to a virtual care platform called Vista Dialog, which facilitated real-time communication between patients and healthcare providers. Glycosylated haemoglobin (HbA1c) levels, time in range (TIR), time below range (TBR), diabetes treatment satisfaction, and quality of life were assessed at baseline and after 6 months.

Results

Baseline characteristics were similar between the intervention and control groups, except for education level, where there was a skewed distribution between the groups (the intervention group had a lower education level). At the 6-month follow-up, there were no significant differences in HbA1c levels, TIR, TBR, or diabetes treatment satisfaction between the two groups. However, the intervention group demonstrated a significant decrease in the burden on physical health compared with the control group, indicating an improved quality of life.

Conclusions

The implementation of a virtual diabetes clinic using the Vista Dialog platform did not result in significant improvements in glycaemic control or treatment satisfaction compared with usual care. However, it did show potential benefits in terms of reducing the burden on physical health and improving quality of life in young adults with type 1 diabetes. Further research is needed to explore the long-term effects and optimal use of virtual clinics in diabetes management.

Trial registration

ISRCTN number: 73,435,627 (registration date: 23/10/2019): https://doi.org/10.1186/ISRCTN73435627. The performance and results of this trial adhere to the guidelines outlined in the CONSORT 2010 (Consolidated Standards of Reporting Trials) recommendations.
Heterogeneity of outcomes in randomized controlled trials on implant prosthodontic therapy is hindering comparative effectiveness research: meta-research study
Authors: Vardić Ante , Puljak Livia , Galić Tea , Viskić Joško , Kuliš Ena , Poklepović Peričić Tina
Published: November 2023

Background

Consistency in outcomes across clinical trials allows for comparing and combining results from different studies. A core outcome set (COS), representing a minimally agreed standardized group of outcomes that should be monitored and measured through research in a specific field of medicine, is not yet available for trials in implant prosthodontic (dental implant) therapy. This meta-research study aimed to analyze outcomes used in clinical trials on implant prosthodontic therapy.

Methods

We searched the Cochrane Oral Health Group (COHG) register to identify systematic reviews of interventions in implant prosthodontic therapy published by October 2023. From the randomized controlled trials (RCTs) included in the relevant reviews, we extracted data on the characteristics of the included trials and the outcomes used. We categorized outcomes into domains.

Results

From 182 systematic reviews in the COHG register, we included 11 systematic reviews on dental implant therapy. The reviews included 117 unique RCTs with 4725 participants, published from 1995 to 2020, which analyzed 74 different outcomes. Using different definitions, implant failure was analyzed in 73 RCTs. Seventeen RCTs did not define implant failure. Failure was most often (30 RCTs) followed up for one year. Only one RCT assessed implant failure after five years. Trials used 17 definitions of implant failure, while 17 trials did not report on the criteria of implant failure. Complications were analyzed in 48 RCTs, although they were not clearly defined in 12 RCTs. Failure of prosthodontic supra-structure was analyzed in 74 RCTs, with definitions of failure and criteria not clearly defined in 44 RCTs. Trials considered adverse events, peri-implant tissue health, patient attitudes, and other outcomes, including cost, aesthetics, or procedure duration. These outcomes were often different between trials. Twenty-six outcomes were used only once per study.

Conclusions

Clinical trials in implant prosthodontics used different outcomes, different definitions of outcomes and used different times to monitor them. Standardization of outcomes is necessary to allow comparability and evidence synthesis about the effectiveness of implant prosthodontic therapy.
Telemedicine perception and interest among medical students at the University of Sharjah, United Arab Emirates, 2023
Authors: Albahri Abdulaziz H. , Alnaqbi Shatha A. , Alnaqbi Shahad A. , Shorbagi Sarra
Published: November 2023

Background

Telemedicine is becoming an integral part of healthcare. Training medical students in telemedicine is encouraged by many medical organizations. However, in the United Arab Emirates in particular, most medical schools have not incorporated it into their curriculum. Therefore, this study aims to assess medical students’ perceptions and interest in telemedicine teaching at the University of Sharjah, UAE.

Methods

A questionnaire-based survey was built based on the current literature and was distributed to all medical students at the University of Sharjah between February and March 2023. The questionnaire assessed the participants for their demographic data, access to and use of digital devices, exposure to and beliefs related to telemedicine, and their medical school experience with distance learning and telemedicine. The data were analyzed via simple statistics, and the Chi-square test was used to assess the associated factors affecting the participants’ interest in receiving telemedicine teaching.

Results

The questionnaire had a 70.4% (547/777) response rate. The mean age (SD) of the participants was 20.7 years (1.57), and the majority were female (68.4%). Over 98% of the students reported having easy access to and being comfortable with using computers and the internet. Most students (90.5%) believed that the medical school curriculum should include teaching in telemedicine; however, 78.2% of these students stated that it should be included as an elective course. The participants’ interest in receiving teaching in telemedicine had a statistically significant association with the following factors: being female, being familiar with telemedicine, having read literature on telemedicine, having beliefs that telemedicine is an opportunity to improve current medical practice, that its use should be encouraged, that it has an important role to play in healthcare, that it does not pose greater threat to current medical practice, having a preference to continue distance learning at medical school and having an interest in incorporating telemedicine in their future careers.

Conclusions

It is an ideal time to incorporate telemedicine into the medical curriculum at the University of Sharjah with most students expressing interest in it. However, further research is needed to assess its applicability to other medical schools in the country and elsewhere.
Proactively tailoring implementation: the case of shared decision-making for lung cancer screening across the VA New England Healthcare Network
Authors: Herbst Abigail N. , McCullough Megan B. , Wiener Renda Soylemez , Barker Anna M. , Maguire Elizabeth M. , Fix Gemmae M.
Published: November 2023

Background

Shared Decision-Making to discuss how the benefits and harms of lung cancer screening align with patient values is required by the US Centers for Medicare and Medicaid and recommended by multiple organizations. Barriers at organizational, clinician, clinical encounter, and patient levels prevent SDM from meeting quality standards in routine practice. We developed an implementation plan, using the socio-ecological model, for Shared Decision-Making for lung cancer screening for the Department of Veterans Affairs (VA) New England Healthcare System. Because understanding the local context is critical to implementation success, we sought to proactively tailor our original implementation plan, to address barriers to achieving guideline-concordant lung cancer screening.

Methods

We conducted a formative evaluation using an ethnographic approach to proactively identify barriers to Shared Decision-Making and tailor our implementation plan. Data consisted of qualitative interviews with leadership and clinicians from seven VA New England medical centers, regional meeting notes, and Shared Decision-Making scripts and documents used by providers. Tailoring was guided by the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS).

Results

We tailored the original implementation plan to address barriers we identified at the organizational, clinician, clinical encounter, and patient levels. Overall, we removed two implementation strategies, added five strategies, and modified the content of two strategies. For example, at the clinician level, we learned that past personal and clinical experiences predisposed clinicians to focus on the benefits of lung cancer screening. To address this barrier, we modified the content of our original implementation strategy Make Training Dynamic to prompt providers to self-reflect about their screening beliefs and values, encouraging them to discuss both the benefits and potential harms of lung cancer screening.

Conclusions

Formative evaluations can be used to proactively tailor implementation strategies to fit local contexts. We tailored our implementation plan to address unique barriers we identified, with the goal of improving implementation success. The FRAME-IS aided our team in thoughtfully addressing and modifying our original implementation plan. Others seeking to maximize the effectiveness of complex interventions may consider using a similar approach.
A pangenome graph reference of 30 chicken genomes allows genotyping of large and complex structural variants
Authors: Rice Edward S. , Alberdi Antton , Alfieri James , Athrey Giridhar , Balacco Jennifer R. , Bardou Philippe , Blackmon Heath , Charles Mathieu , Cheng Hans H. , Fedrigo Olivier , Fiddaman Steven R. , Formenti Giulio , Frantz Laurent A. F. , Gilbert M. Thomas P. , Hearn Cari J. , Jarvis Erich D. , Klopp Christophe , Marcos Sofia , Mason Andrew S. , Velez-Irizarry Deborah , Xu Luohao , Warren Wesley C.
Published: November 2023

Background

The red junglefowl, the wild outgroup of domestic chickens, has historically served as a reference for genomic studies of domestic chickens. These studies have provided insight into the etiology of traits of commercial importance. However, the use of a single reference genome does not capture diversity present among modern breeds, many of which have accumulated molecular changes due to drift and selection. While reference-based resequencing is well-suited to cataloging simple variants such as single-nucleotide changes and short insertions and deletions, it is mostly inadequate to discover more complex structural variation in the genome.

Methods

We present a pangenome for the domestic chicken consisting of thirty assemblies of chickens from different breeds and research lines.

Results

We demonstrate how this pangenome can be used to catalog structural variants present in modern breeds and untangle complex nested variation. We show that alignment of short reads from 100 diverse wild and domestic chickens to this pangenome reduces reference bias by 38%, which affects downstream genotyping results. This approach also allows for the accurate genotyping of a large and complex pair of structural variants at the K feathering locus using short reads, which would not be possible using a linear reference.

Conclusions

We expect that this new paradigm of genomic reference will allow better pinpointing of exact mutations responsible for specific phenotypes, which will in turn be necessary for breeding chickens that meet new sustainability criteria and are resilient to quickly evolving pathogen threats.
Circular RNAs in renal cell carcinoma: from mechanistic to clinical perspective
Authors: Huang Chunjie , Esfani Sarafraz Pooya , Enayati Parisa , Mortazavi Mamaghani Elham , Babakhanzadeh Emad , Nazari Majid
Published: November 2023

CircRNAs, a special type of noncoding RNAs characterized by their stable structure and unique abilities to form backsplicing loops, have recently attracted the interest of scientists. These RNAs are abundant throughout the body and play important roles such as microRNA sponges, templates for transcription, and regulation of protein translation and RNA-binding proteins. Renal cancer development is highly correlated with abnormal circRNA expression in vivo. CircRNAs are currently considered promising targets for novel therapeutic approaches as well as possible biomarkers for prognosis and diagnosis of various malignancies. Despite our growing understanding of circRNA, numerous questions remain unanswered. Here, we address the characteristics of circRNAs and their function, focusing in particular on their impact on drug resistance, metabolic processes, metastasis, cell growth, and programmed cell death in renal cancer. In addition, the application of circRNAs as prognostic and diagnostic biomarkers will be discussed.
Biomimetic platelet-camouflaged drug-loaded polypyrrole for the precise targeted antithrombotic therapy
Authors: Zhao Zhining , Li Xiaodan , Wang Yan , Liu Cheng , Ling Guixia , Zhang Peng
Published: November 2023

Lower extremity deep venous thrombosis (LEDVT) affects patient’s quality of life for a long time, and even causes pulmonary embolism, which threatens human health. Current anticoagulant drugs in clinical treatment are hampered by the risk of bleeding due to poor targeting and low drug penetration. Here, we used platelet (PLT)-like biological targeting to enhance the delivery and accumulation of nanomedicines in thrombus and reduce the risk of bleeding. Meanwhile, the parallel strategy of “thrombus thermal ablation and anticoagulation” was applied to increase the permeability of drugs in thrombus and achieve the optimal antithrombotic effect. Polypyrrole (PPy) and rivaroxban (Riv, an anticoagulant drug) were co-assembled into platelet membrane-coated nanoparticles (NPs), PLT-PPy/Riv NPs, which actively targeted the thrombotic lesion at multiple targets in the platelet membrane and were thermally and drug-specific thrombolysed by 808 nm laser irradiation. The combination therapy resulted in up to 90% thrombolysis in a femoral vein thrombosis model compared to single phototherapy or drug therapy. The results showed that the nanoformulation provided a new direction for remote precise and controlled sustained thrombolysis, which was in line with the trend of nanomedicine towards clinical translation.
In vitro maturation (IVM) of human immature oocytes: is it still relevant?
Authors: Das Mausumi , Son Weon-Young
Published: November 2023

In vitro maturation (IVM) of human immature oocytes has been shown to be a viable option for patients at risk of ovarian hyperstimulation syndrome (OHSS), those seeking urgent fertility preservation and in circumstances where controlled ovarian stimulation is not feasible. Moreover, IVM techniques can be combined with ovarian tissue cryobanking to increase the chances of conception in cancer survivors. The clinical applications of IVM in the field of reproductive medicine are rapidly expanding and the technique is now classified as non-experimental. In contrast to conventional IVF (in vitro fertilization), IVM offers several advantages, such as reduced gonadotropin stimulation, minimal risk of ovarian hyperstimulation syndrome (OHSS), reduced treatment times and lower costs. However, the technical expertise involved in performing IVM and its lower success rates compared to traditional IVF cycles, still pose significant challenges. Despite recent advances, such as innovative biphasic IVM systems, IVM is still an evolving technique and research is ongoing to refine protocols and identify techniques to improve its efficiency and effectiveness. A comprehensive understanding of the distinct mechanisms of oocyte maturation is crucial for obtaining more viable oocytes through in vitro methods, which will in turn lead to significantly improved success rates. In this review, the present state of human IVM programs and future research directions will be discussed, aiming to promote a better understanding of IVM and identify potential strategies to improve the overall efficiency and success rates of IVM programs, which will in turn lead to better clinical outcomes.
Entomophagy practices, use patterns, and factors influencing perception and consumption frequency of edible insects in the Republic of Benin
Authors: Anagonou Corinne Mèdéou , Loko Laura Estelle Yêyinou , Dassou Anicet Gbeblonoudo , Toffa Joelle , Djegbe Innocent , Saliou Manzid , Dansi Alexandre
Published: November 2023

Background

Edible insects are important sources of essential nutrients and have the potential to contribute to malnutrition reduction and food security in the Republic of Benin. However, their consumption is always restricted to a limited number of sociocultural groups. To determine how the consumption of insects could be promoted as an alternative food source, this study documents the endogenous knowledge associated with edible insects and, the main factors that govern their perception and frequency consumption.

Methods

A survey was conducted towards 479 rural households consuming edible insects through 91 villages of Atacora, Alibori, Zou, and Plateau departments using individual interviews with a semi-structured questionnaire. The survey was focused on the inventory of edible insects and the documentation of consumers’ acceptance, frequencies and motive reason of consumption, local uses, and accessibility to edible insects. Samples of edible insects were collected and preserved in 70% alcohol for taxonomic identification.

Results

The majority of surveyed people (79.1%) were consumers of edible insects since many years ago (29.1 ± 17.2 years). Insect species belonging to 17 genera of 7 families and 3 orders of insects were used as food, with Brachytrupes membranaceus Drury being the most widespread and consumed. Six factors affecting edible insect availability were identified with the chemical pollution as the most important. Besides their food use (63.2%), edible insects in the study area were used for several purposes. We find that ethnicity, religion, age, education level, and monthly frequency of insect consumption are the main factors influencing the local perception of edible insects. Indeed ethnic group, religion ethnicity, and market accessibility have a positive influence on edible insect consumption frequency. The Hierarchical Clustering of Principal Components has allowed us to classify the interviewees into 3 groups with different perceptions of entomophagy and their characteristics will make it possible to better orient the strategies for promoting entomophagy in the Republic of Benin.

Conclusions

Religion and tradition are among the main factors that influence entomophagy in Benin Republic. The development of a national strategy to promote entomophagy should take into account the recorded insect consumption motivations, and their different uses by each ethnic group, and mainly target young people.
Direct inhibition of dioxygenases TET1 by the rheumatoid arthritis drug auranofin selectively induces cancer cell death in T-ALL
Authors: Chen Long , Ren Anqi , Zhao Yuan , Chen Hangyu , Wu Qifang , Zheng Mengzhu , Zhang Zijian , Zhang Tongcun , Zhong Wu , Lin Jian , Zhu Haichuan
Published: November 2023

T-cell acute lymphoblastic leukemia (T-ALL) is a type of hematologic tumor with malignant proliferation of hematopoietic progenitor cells. However, traditional clinical treatment of T-ALL included chemotherapy and stem cell transplantation always lead to recurrence and poor prognosis, thus new therapeutic targets and drugs are urgently needed for T-ALL treatment. In this study, we showed that TET1 (ten-eleven translocation 1), a key participant of DNA epigenetic control, which catalyzes the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) to modulate gene expression, was highly upregulated in human T-ALL and negatively correlated with the prognosis of patients. Knockdown of TET1 suppressed T-ALL growth and progression, suggesting that TET1 inhibition maybe an effective way to fight T-ALL via DNA epigenetic modulation. Combining structure-guided virtual screening and cell-based high-throughput screening of FDA-approved drug library, we discovered that auranofin, a gold-containing compound, is a potent TET1 inhibitor. Auranofin inhibited the catalytic activity of TET1 through competitive binding to its substrates binding pocket and thus downregulated the genomic level of 5hmC marks and particularly epigenetically reprogramed the expression of oncogene c-Myc in T-ALL in TET1-dependent manner and resulted in suppression of T-ALL in vitro and in vivo. These results revealed that TET1 is a potential therapeutic target in human T-ALL and elucidated the mechanism that TET1 inhibitor auranofin suppressed T-ALL through the TET1/5hmC/c-Myc signaling pathway. Our work thus not only provided mechanism insights for T-ALL treatment, but also discovered potential small molecule therapeutics for T-ALL.
Deciphering tumor immune microenvironment differences between high-grade serous and endometrioid ovarian cancer to investigate their potential in indicating immunotherapy response
Authors: Yang Hua , Gu Xiangyu , Fan Rong , Zhu Qun , Zhong Sen , Wan Xirun , Chen Qian , Zhu Lan , Feng Fengzhi
Published: November 2023

Background

Ovarian cancer is a significant public health concern with a poor prognosis for epithelial ovarian cancer. To explore the potential of immunotherapy in treating epithelial ovarian cancer, we investigated the immune microenvironments of 52 patients with epithelial ovarian cancer, including 43 with high-grade serous ovarian cancer and 9 with endometrioid ovarian cancer.

Results

Fresh tumor tissue was analyzed for genetic mutations and various parameters related to immune evasion and infiltration. The mean stromal score (stromal cell infiltration) in high-grade serous ovarian cancer was higher than in endometrioid ovarian cancer. The infiltration of CD8 T cells and exhausted CD8 T cells were found to be more extensive in high-grade serous ovarian cancer. Tumor Immune Dysfunction and Exclusion scores, T cell exclusion scores, and cancer-associated fibroblasts (CAF) scores were also higher in the high-grade serous ovarian cancer group, suggesting that the number of cytotoxic lymphocytes in the tumor microenvironment of high-grade serous ovarian cancer is likely lower compared to endometrioid ovarian cancer.

Conclusions

The high mean stromal score and more extensive infiltration and exhaustion of CD8 T cells in high-grade serous ovarian cancer indicate that high-grade serous ovarian cancer exhibits a higher level of cytotoxic T cell infiltration, yet these T cells tend to be in a dysfunctional state. Higher Tumor Immune Dysfunction and Exclusion scores, T cell exclusion scores, and CAF scores in high-grade serous ovarian cancers suggest that immune escape is more likely to occur in high-grade serous ovarian cancer, thus endometrioid ovarian cancer may be more conducive to immunotherapy. Therefore, it is crucial to design immunotherapy clinical trials for ovarian cancer to distinguish between high-grade serous and endometrioid ovarian cancer from the outset. This distinction will help optimize treatment strategies and improve outcomes for patients with different subtypes.
Differential expression pattern of Bcl-2 family members in B and T cells in systemic lupus erythematosus and rheumatoid arthritis
Authors: Kielbassa K , Van der Weele L , Voskuyl AE , de Vries N , Eldering E , Kuijpers TW
Published: November 2023

Objective

This study aimed to evaluate the expression level of anti-apoptotic Bcl-2 family proteins in B and T cells in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in relation to disease activity and the effect of various Bcl-2 family inhibitors (BH3 mimetics) as potential treatment.

Methods

We included 14 SLE patients, 12 RA patients, and 13 healthy controls to study anti-apoptotic Bcl-2, Bcl-XL, and Mcl-1 expression and cell survival in different B and T cell subsets using stimulation assays and intracellular flow cytometry. Effect of various BH3 mimetics was assessed by cell viability analyses.

Results

In SLE, significant differences in Bcl-2 family members were confined to the B cell compartment with decreased induction of Bcl-XL (p ≤ 0.05) and Mcl-1 (p ≤ 0.001) upon CpG stimulation. In RA, we did not observe any differences in expression levels of Bcl-2 family proteins. Expression patterns did not correlate with disease activity apart from decreased induction of Mcl-1 in B cells in active SLE. After in vitro stimulation with CpG, plasmablasts were more viable after treatment with three different BH3 mimetics compared to naïve or memory B cells in control and patient cells. After activation, Mcl-1 inhibition was most effective in reducing plasmablast and T cell viability, however, less in patients than controls.

Conclusion

Our study provides evidence for the increased differential expression pattern of Bcl-2 family members in B and T cell subsets of patients with SLE compared to controls. Tested BH3 mimetics showed higher efficacy in controls compared to both autoimmune diseases, though nonsignificant due to low patient numbers.