bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer immune evasion through KRAS and PD-L1 and potential therapeutic interventions
Authors: Watterson Alex , Coelho Matthew A.
Published: March 2023

Oncogenic driver mutations have implications that extend beyond cancer cells themselves. Aberrant tumour cell signalling has various effects on the tumour microenvironment and anti-tumour immunity, with important consequences for therapy response and resistance. We provide an overview of how mutant RAS, one of the most prevalent oncogenic drivers in cancer, can instigate immune evasion programs at the tumour cell level and through remodelling interactions with the innate and adaptive immune cell compartments. Finally, we describe how immune evasion networks focused on RAS, and the immune checkpoint molecule PD-L1 can be disrupted through therapeutic intervention, and discuss potential strategies for combinatorial treatment.
Lactoferrin suppresses the progression of colon cancer under hyperglycemia by targeting WTAP/m6A/NT5DC3/HKDC1 axis
Authors: Li Huiying , Li Chaonan , Zhang Boyang , Jiang Hongpeng
Published: March 2023

Background

Although the relationship between type 2 diabetes (T2D) and the increased risk of colorectal carcinogenesis is widely defined in clinical studies, the therapeutic methods and molecular mechanism of T2D-induced colon cancer and how does hyperglycemia affect the progression is still unknown. Here, we studied the function of lactoferrin (LF) in suppressing the progression of colon cancer in T2D mice, and uncovered the related molecular mechanisms in DNA 5mC and RNA m6A levels.

Methods

We examined the effects of LF (50% iron saturation) on the migration and invasion of colon tumor cells under high concentration of glucose. Then, transcriptomics and DNA methylation profilings of colon tumor cells was co-analyzed to screen out the special gene (NT5DC3), and the expression level of NT5DC3 in 75 clinical blood samples was detected by q-PCR and western blot, to investigate whether NT5DC3 was a biomarker to distinguish T2D patients and T2D-induced colon cancer patients from healthy volunteers. Futhermore, in T2D mouse with xenografted colon tumor models, the inhibitory effects of LF and NT5DC3 protein on colon tumors were investigated. In addition, epigenetic alterations were measured to examine the 5mC/m6A modification sites ofNT5DC3regulated by LF. Utilizing siRNA fragments of eight m6A-related genes, the special gene (WTAP) regulating m6A ofNT5DCwas proved, and the effect of LF onWTAP/NT5DC3/HKDC1axis was finally evaluated.

Results

A special geneNT5DC3was screened out through co-analysis of transcriptomics and DNA methylation profiling, andHKDC1might be a downstream sensor ofNT5DC3. Mechanistically, LF-dependent cellular DNA 5mC and RNA m6A profiling remodeling transcriptionally regulate NT5DC3 expression.WTAPplays a key role in regulatingNT5DC3m6A modification and subsequently controlsNT5DC3downstream targetHKDC1expression. Moreover, co-treatment of lactoferrin and NT5DC3 protein restrains the growth of colon tumors by altering the aberrant epigenetic markers. Strikingly, clinical blood samples analysis demonstrates NT5DC3 protein expression is required to direct the distinction of T2D or T2D-induced colon cancer with healthy humans.

Conclusions

Together, this study reveals that lactoferrin acts as a major factor to repress the progression of colon cancer under hyperglycemia, thus, significantly expanding the landscape of natural dietary mediated tumor suppression.

Graphical Abstract
MiR-200/183 family-mediated module biomarker for gastric cancer progression: an AI-assisted bioinformatics method with experimental functional survey
Authors: Yan Wenying , Chen Yuqi , Hu Guang , Shi Tongguo , Liu Xingyi , Li Juntao , Sun Linqing , Qian Fuliang , Chen Weichang
Published: March 2023

Background

Gastric cancer (GC) is a major cancer burden throughout the world with a high mortality rate. The performance of current predictive and prognostic factors is still limited. Integrated analysis is required for accurate cancer progression predictive biomarker and prognostic biomarkers that help to guide therapy.

Methods

An AI-assisted bioinformatics method that combines transcriptomic data and microRNA regulations were used to identify a key miRNA-mediated network module in GC progression. To reveal the module’s function, we performed the gene expression analysis in 20 clinical samples by qRT-PCR, prognosis analysis by multi-variable Cox regression model, progression prediction by support vector machine, and in vitro studies to elaborate the roles in GC cells migration and invasion.

Results

A robust microRNA regulated network module was identified to characterize GC progression, which consisted of seven miR-200/183 family members, five mRNAs and two long non-coding RNAs H19 and CLLU1. Their expression patterns and expression correlation patterns were consistent in public dataset and our cohort. Our findings suggest a two-fold biological potential of the module: GC patients with high-risk score exhibited a poor prognosis (p-value < 0.05) and the model achieved AUCs of 0.90 to predict GC progression in our cohort. In vitro cellular analyses shown that the module could influence the invasion and migration of GC cells.

Conclusions

Our strategy which combines AI-assisted bioinformatics method with experimental and clinical validation suggested that the miR-200/183 family-mediated network module as a “pluripotent module”, which could be potential marker for GC progression.
Breast metastasis in high-grade endometrial stromal sarcoma (HG-ESS) with BCOR rearrangement: a case report of a novel metastatic site
Authors: Fong Ashlyn , Offman Saul
Published: March 2023

Background

The ZC3H7B-BCOR fusion gene has recently been described in tumours with kinship to so-called high grade endometrial stromal sarcoma (HG-ESS). This subset of tumour behaves similarly to YWHAE-NUTM2A/B HG-ESS, however, they are both morphologically and immunophenotypically distinct neoplasms. The identified rearrangements in the BCOR gene have been accepted as both the driver and requisite feature in creating a novel sub-entity within the category of HG-ESS.

Preliminary investigations into BCOR HG-ESS have shown similar outcomes to YWHAE-NUTM2A/B HG-ESS, with patients typically presenting with high stage disease. Clinical recurrences and metastases to lymph nodes, sacrum/bone, pelvis/peritoneum, lung, bowel and skin have been identified. In this report, we describe a case of BCOR HG-ESS, that is deeply myoinvasive and widely metastatic. Metastatic deposits include a mass in the breast discovered on self-examination; a metastatic site that has yet to be reported in the literature.

Case presentation

A 59-year-old female underwent biopsy for post-menopausal bleeding, yielding a diagnosis of “low-grade spindle cell neoplasm with myxoid stroma and endometrial glands”, favouring endometrial stromal sarcoma (ESS). She was then referred for total hysterectomy and bilateral salpingo-oophorectomy. The resected uterine neoplasm was both intracavitary and deeply myoinvasive with morphology consistent with that of the biopsy specimen. Characteristic immunohistochemistry (IHC) was noted, and fluorescence in situ hybridization confirmed BCOR rearrangement, supporting a diagnosis of BCOR HG-ESS. A few months postoperatively, the patient underwent needle core biopsy of the breast which revealed metastatic HG-ESS.

Conclusions

This case highlights some of the diagnostic challenges posed by uterine mesenchymal neoplasms, and exemplifies the emerging histomorphologic, immunohistochemical, molecular and clinicopathologic features of the recently described HG-ESS with ZC3H7B-BCOR fusion. It adds to the body of evidence supporting the inclusion of BCOR HG-ESS as a sub-entity of HG-ESS within the endometrial stromal and related tumours subcategory of uterine mesenchymal tumors, as well as the poor prognosis and high metastatic potential of this tumor.
Machine learning identification of thresholds to discriminate osteoarthritis and rheumatoid arthritis synovial inflammation
Authors: Mehta Bella , Goodman Susan , DiCarlo Edward , Jannat-Khah Deanna , Gibbons J. Alex B. , Otero Miguel , Donlin Laura , Pannellini Tania , Robinson William H. , Sculco Peter , Figgie Mark , Rodriguez Jose , Kirschmann Jessica M. , Thompson James , Slater David , Frezza Damon , Xu Zhenxing , Wang Fei , Orange Dana E.
Published: March 2023

Background

We sought to identify features that distinguish osteoarthritis (OA) and rheumatoid arthritis (RA) hematoxylin and eosin (H&E)-stained synovial tissue samples.

Methods

We compared fourteen pathologist-scored histology features and computer vision-quantified cell density (147 OA and 60 RA patients) in H&E-stained synovial tissue samples from total knee replacement (TKR) explants. A random forest model was trained using disease state (OA vs RA) as a classifier and histology features and/or computer vision-quantified cell density as inputs.

Results

Synovium from OA patients had increased mast cells and fibrosis (p < 0.001), while synovium from RA patients exhibited increased lymphocytic inflammation, lining hyperplasia, neutrophils, detritus, plasma cells, binucleate plasma cells, sub-lining giant cells, fibrin (all p < 0.001), Russell bodies (p = 0.019), and synovial lining giant cells (p = 0.003). Fourteen pathologist-scored features allowed for discrimination between OA and RA, producing a micro-averaged area under the receiver operating curve (micro-AUC) of 0.85±0.06. This discriminatory ability was comparable to that of computer vision cell density alone (micro-AUC = 0.87±0.04). Combining the pathologist scores with the cell density metric improved the discriminatory power of the model (micro-AUC = 0.92±0.06). The optimal cell density threshold to distinguish OA from RA synovium was 3400 cells/mm2, which yielded a sensitivity of 0.82 and specificity of 0.82.

Conclusions

H&E-stained images of TKR explant synovium can be correctly classified as OA or RA in 82% of samples. Cell density greater than 3400 cells/mm2 and the presence of mast cells and fibrosis are the most important features for making this distinction.
DNA methylation as a potential mediator of the association between indoor air pollution and neurodevelopmental delay in a South African birth cohort
Authors: Feil Dakotah , Abrishamcar Sarina , Christensen Grace M. , Vanker Aneesa , Koen Nastassja , Kilanowski Anna , Hoffman Nadia , Wedderburn Catherine J. , Donald Kirsten A. , Kobor Michael S. , Zar Heather J. , Stein Dan J. , Hüls Anke
Published: March 2023

Background

Exposure to indoor air pollution during pregnancy has been linked to neurodevelopmental delay in toddlers. Epigenetic modification, particularly DNA methylation (DNAm), may explain this link. In this study, we employed three high-dimensional mediation analysis methods (HIMA, DACT, and gHMA) followed by causal mediation analysis to identify differentially methylated CpG sites and genes that mediate the association between indoor air pollution and neurodevelopmental delay. Analyses were performed using data from 142 mother to child pairs from a South African birth cohort, the Drakenstein Child Health Study. DNAm from cord blood was measured using the Infinium MethylationEPIC and HumanMethylation450 arrays. Neurodevelopment was assessed at age 2 years using the Bayley Scores of Infant and Toddler Development, 3rd edition across four domains (cognitive development, general adaptive behavior, language, and motor function). Particulate matter with an aerodynamic diameter of 10 μm or less (PM10) was measured inside participants’ homes during the second trimester of pregnancy.

Results

A total of 29 CpG sites and 4 genes (GOPC, RP11-74K11.1, DYRK1A, RNMT) were identified as significant mediators of the association between PM10 and cognitive neurodevelopment. The estimated proportion mediated (95%-confidence interval) ranged from 0.29 [0.01, 0.86] for cg00694520 to 0.54 [0.11, 1.56] for cg05023582.

Conclusions

Our findings suggest that DNAm may mediate the association between prenatal PM10 exposure and cognitive neurodevelopment. DYRK1A and several genes that our CpG sites mapped to, including CNKSR1, IPO13, IFNGR1, LONP2, and CDH1, are associated with biological pathways implicated in cognitive neurodevelopment and three of our identified CpG sites (cg23560546 [DAPL1], cg22572779 [C6orf218], cg15000966 [NT5C]) have been previously associated with fetal brain development. These findings are novel and add to the limited literature investigating the relationship between indoor air pollution, DNAm, and neurodevelopment, particularly in low- and middle-income country settings and non-white populations.
Unique considerations for the medical care of restrictive eating disorders in children and young adolescents
Authors: Tanner Anna B.
Published: March 2023

Background

The medical complications of eating disorders are often approached through an age-neutral lens. However, children and young adolescents may have unique medical complications related to the energy needs and timing of growth and development. Providers caring for patients in this vulnerable age range should understand how to identify, approach, and manage these potential age-related complications.

Review

Evidence continues to accumulate that increasingly younger patients are being diagnosed with eating disorders. These children and young adolescents have significant risk for unique and potentially irreversible medical complications. Without early identification and treatment, restrictive eating disorders may negatively impact linear growth, bone development and brain maturation in children and young adolescents. Additionally, due to the energy needs of growth and development, unique considerations exist for the use of acute medical stabilization and the identification of patients at risk for refeeding syndrome with initial nutritional rehabilitation. This review presents an approach to the evaluation and management of children and young adolescents with eating disorders.

Conclusion

Children and young adolescents with restrictive eating disorders may have unique medical complications related to the energy needs and timing of linear growth and pubertal development. Significant risk exists for irreversible medical complications of impaired growth, bone, and brain health. Increased awareness of the energy needs for growth and development may improve early recognition, appropriate intervention, and future outcomes for children and young adolescents with restrictive eating disorders.
A long-term survival case of histiocytic sarcoma by surgery alone in a Japanese elderly breast tumor patient
Authors: Higuchi Toru , Li Chih-Ping , Hirota Yuko , Hayashi Yuji , Arisawa Fumio , Manabe Ikuko , Sakurai Takashi , Adachi Akiko , Saito Tsuyoshi
Published: March 2023

Introduction

Histiocytic sarcoma (HS) is a rare hematologic malignancy. HS of the breast is extremely rare, and we present a case of an elderly patient with breast HS.

Case presentation

An 81-year-old woman with unremarkable past medical and family histories presented to our hospital with a palpable mass in her right upper breast. She had noticed a mass in her right breast 3 months before her first visit. Physical examination revealed a mass measuring approximately 30 mm in the right upper quadrant of the breast; there were no cervical or axillary lymphadenopathies. Mammography revealed a high-concentration mass with unclear margins in the upper and outer breast. Ultrasound and magnetic resonance imaging (MRI) revealed a 31 × 23-mm nodule with a relatively clear margin and necrotic sign on the T2-intensified image. A mastectomy was performed upon the patient’s request, and the surgical specimen revealed a 35-mm hemorrhagic mass. The lesion was estrogen receptor-, progesterone receptor-, and HER2/neu-negative. The Ki-67 labeling index was approximately 30%. The immunohistochemical panel showed immune reactivity for the histiocytic markers CD68, CD163, and CD206 and was immune-negative for B lineage, T lineage, Langerhans cells, and keratins. The diagnosis of HS was based on the morphological and immunophenotypic characteristics of the mass. The patient received no systemic therapy and survived for 50 months without recurrence.

Conclusions

Here, we report the case of an elderly patient with rare breast HS. Although the prognosis of HS seems poor, the breast HS was not as poor as expected, since it might have been discovered in the local region before it metastasized.
Knowledge, and practices on sexual and reproductive health among youth trainees attached to youth training centers in Sri Lanka
Authors: Mataraarachchi D. , Vithana P. V. S. C. , Lokubalasooriya A. , Jayasundara C. J. , Suranutha A. S. , Pathirana T. E. A. , De Silva C.
Published: March 2023

Background

Sexual and reproductive health is a major concern among adolescents and youth in Sri Lanka. The study was carried out to assess the knowledge, and practices of the youth trainees attached to youth training institutes in Sri Lanka.

Methodology

A descriptive, cross-sectional study was carried out among randomly selected 425 youth trainees attached to youth training centers in Sri Lanka using a pre-tested self-administered questionnaire. Statistical analysis was conducted using SPSS-21. Categorical variables were presented as numbers and percentages. A comparison of categorical variables was conducted using the Chi-Square test and Fisher’s exact test as applicable. The bivariate logistic regression model was used to determine the independent association of the selected demographic factors with youth trainees’ sexual and reproductive health knowledge.

Results

Study group consisted of 51.8% (n = 220) males and 48.2% (n = 205) females with a mean age of 18.6 years (SD = 1.8). Youth trainees’ knowledge of the physiology of the reproductive tract was not at a satisfactory level, where Only 49% (n = 211) knew that nocturnal emission is normal in young men. The trainee’s knowledge of contraception was also at a poor level. Only 47.5% (n = 202) had ever heard of condoms, and 13.2% (n = 56) knew about the emergency contraceptive pill. Nearly 8% (n = 33) of the youth had engaged in sexual intercourse at least once in their lifetime. Male gender (AOR = 2.3, p < 0.001), and age above 20 years (AOR = 1.9, P = 0.005) were positively associated with SRH knowledge.

Conclusions and recommendations

Knowledge and practices on sexual and reproductive health among youth trainees were sub-standard. The study recommends strengthening sexual and reproductive health education at youth training centers.
Post-mortem interval of buried homicides in Okuku, Nigeria
Authors: Onyejike Darlington Nnamdi , Fischer Victor Adolf , Esomonu Ugochukwu Godfrey , Onyejike Ifeoma Miracle
Published: March 2023

Background

Post-mortem interval estimation of carcasses buried in shallow graves is a grey area in Nigerian forensic investigations. Most of the investigations and court decisions on the time of death of concealed homicides are based on assumptions in Nigeria. Therefore, this study investigated the post-mortem interval of buried remains in Okuku, Cross River State of Nigeria using porcine models. This study also provided a model account of the pattern and timeline of decomposition of buried remains in Nigeria.

Results

Four stages of decomposition were identified within the study period which includes fresh, bloat, active decay, and advanced decay stages. Features of bloat stage of decomposition include bloating of the animals and release of putrid odour. The active decay stage was characterized by the absence of maggots, bone exposure, and greyish discolouration of the body. The advanced decay stage of decomposition is characterized by adipocere formation, fungi activities, and bone exposure.

Conclusions

Buried bodies do not completely skeletonize within 168 days in a typical Nigerian savannah region. Bloat stage started by the 7th day; the active decay stage started by the 14th day. The fresh stage of decay lasted up to 7 days; the bloat stage lasted for 14 days. The active decay stage lasted about 35 days, and the advanced decay stage started at about the 56th day and progressed until the end of the study.
Influence of benign prostatic hyperplasia patterns detected with MRI on the clinical outcome after prostatic artery embolization
Authors: Boschheidgen Matthias , Al-Monajjed Rouvier , Minko Peter , Jannusch Kai , Ullrich Tim , Radke Karl Ludger , Michalski Rene , Radtke Jan Philipp , Albers Peter , Antoch Gerald , Schimmöller Lars
Published: March 2023

Background

To investigate the influence of benign prostatic hyperplasia (BPH) patterns detected with MRI on clinical outcomes after prostatic artery embolization (PAE).

Materials & methods

This retrospective study included 71 consecutive patients with lower urinary tract symptoms (LUTS), who underwent magnetic resonance imaging (MRI) of the prostate followed by PAE at a single centre. MRI scans were evaluated and BPH patterns were determined according to Wasserman type and a modified BPH classification. Additionally, scans were evaluated regarding the presence of adenomatous-dominant benign prostatic hyperplasia (AdBPH). LUTS were assessed using the International Prostate Symptom Score (IPSS) and urinary flow rate (Qmax). Follow-up examination included MRI and clinical outcome.

Results

For clinical outcome at follow-up, IPSS showed median reduction of 54% (IQR 41—75%) and Qmax improved by 4.1 ml/s. We noted significant reduction in volume, intraprostatic protrusion, and prostatic urethral angle in our collective (p < 0.01). Median volume reduction was 25% (IQR 15%—34%). Bilateral embolization was a significant predictor for volume reduction at follow-up. Multiple linear regression analysis showed significant effect of high initial volume on reduction in IPSS after treatment (p < 0.01). Presence of AdBPH was significantly associated with both, volume loss and clinical improvement in terms of IPSS reduction (p < 0.01). Neither BPH pattern based on the Wassermann type nor modified BPH classification were significantly related with postinterventional IPSS and volume loss.

Conclusions

Men benefit from PAE regardless the macroscopic BPH MRI pattern. Preinterventional prostate volume and presence of AdBPH on MRI should be considered for outcome prognosis after PAE.
An ensemble deep learning based IDS for IoT using Lambda architecture
Authors: Alghamdi Rubayyi , Bellaiche Martine
Published: March 2023

The Internet of Things (IoT) has revolutionized our world today by providing greater levels of accessibility, connectivity and ease to our everyday lives. It enables massive amounts of data to be traversed across multiple heterogeneous devices that are all interconnected. This phenomenon makes IoT networks vulnerable to various network attacks and intrusions. Building an Intrusion Detection System (IDS) for IoT networks is challenging as they enable a massive amount of data to be aggregated, which is difficult to handle and analyze in real time mainly because of the heterogeneous nature of IoT devices. This inefficient, traditional IDS approach accentuates the need to develop advanced IDS techniques by employing Machine or Deep Learning. This paper presents a deep ensemble-based IDS using Lambda architecture by following a multi-pronged classification approach. Binary classification uses Long Short Term Memory (LSTM) to differentiate between malicious and benign traffic, while the multi-class classifier uses an ensemble of LSTM, Convolutional Neural Network and Artificial Neural Network classifiers to detect the type of attacks. The model training is performed in the batch layer, while real-time evaluation is carried out through model inferences in the speed layer of the Lambda architecture. The proposed approach gives high accuracy of over 99.93% and saves useful processing time due to the multi-pronged classification strategy and using the lambda architecture.
Wavelet image scattering based glaucoma detection
Authors: Agboola Hafeez Alani , Zaccheus Jesuloluwa Emmanuel
Published: March 2023

Background

The ever-growing need for cheap, simple, fast, and accurate healthcare solutions spurred a lot of research activities which are aimed at the reliable deployment of artificial intelligence in the medical fields. However, this has proved to be a daunting task especially when looking to make automated diagnoses using biomedical image data. Biomedical image data have complex patterns which human experts find very hard to comprehend. Against this backdrop, we applied a representation or feature learning algorithm: Invariant Scattering Convolution Network or Wavelet scattering Network to retinal fundus images and studied the the efficacy of the automatically extracted features therefrom for glaucoma diagnosis/detection. The influence of wavelet scattering network parameter settings as well as 2-D channel image type on the detection correctness is also examined. Our work is a distinct departure from the usual method where wavelet transform is applied to pre-processed retinal fundus images and handcrafted features are extracted from the decomposition results. Here, the RIM-ONE DL image dataset was fed into a wavelet scattering network developed in the Matlab environment to achieve a stage-wise decomposition process called wavelet scattering of the retinal fundus images thereby, automatically learning features from the images. These features were then used to build simple and computationally cheap classification algorithms.

Results

Maximum detection correctness of 98% was achieved on the held-out test set. Detection correctness is highly sensitive to scattering network parameter setting and 2-D channel image type.

Conclusion

A superficial comparison of the classification results obtained from our work and those obtained using a convolutional neural network underscores the potentiality of the proposed method for glaucoma detection.
A peek behind the curtain in the diagnosis and management of COVID‑19‑Associated Mucormycosis (CAM)
Authors: Osman Nermin A. , Anwar Mohammed Moustapha , Singh Bivek , Gupta Girish K. , Rabie Amgad M.
Published: March 2023

Coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) is responsible for a high mortality rate due to its unique and severe host-pathogen interactions. Critically ill or immunocompromised COVID-19 patients are more prone to suffer from aggressive mycoses. Probable victims include those with uncontrolled diabetes mellitus (DM), metabolic acidosis, prolonged neutropenia, increased ferritin levels, hypoxia, and prolonged hospitalization with/without mechanical ventilators and corticosteroids administration. The current review aims to outline the journey of patients with CAM as well as the advantages and disadvantages of the currently available diagnostic techniques. It also discussed the current status of treatment options and caveats in the management of mucormycosis. Multidisciplinary team, early diagnosis, controlling the predisposing condition(s), complete surgical debridement, effective antifungal therapies (e.g., amphotericin B, isavuconazole, and posaconazole), and implementing antifungal stewardship programs are imperative in CAM cases.
Liquid Biopsies for Circulating Tumor DNA Detection May Reveal Occult Hematologic Malignancies in Patients With Solid Tumors
Authors: Aldea Mihaela , Tagliamento Marco , Bayle Arnaud , Vasseur Damien , Vergé Véronique , Marinello Arianna , Danlos François-Xavier , Blanc-Durand Felix , Bernard Elsa , Cerbone Luigi , Mosele Maria Fernanda , Renneville Aline , Hadoux Julien , Loriot Yohann , Sakkal Madona , Vozy Aurore , Sarkozy Clementine , Smolenschi Cristina , Nicotra Claudio , Martin-Romano Patricia , Boccon-Gibod Clementine , Habza Wafikaamira , Lazarovici Julien , Ponce Santiago , Hollebecque Antoine , Marzac Christophe , Lacroix Ludovic , Barlesi Fabrice , André Fabrice , Besse Benjamin , Rouleau Etienne , Italiano Antoine , Micol Jean-Baptiste
Published: March 2023

PURPOSE

High-risk clonal hematopoiesis (CH) is frequently incidentally found in patients with solid tumors undergoing plasma cell–free DNA sequencing. Here, we aimed to determine if the incidental detection of high-risk CH by liquid biopsy may reveal occult hematologic malignancies in patients with solid tumors.

MATERIALS AND METHODS

Adult patients with advanced solid cancers enrolled in the Gustave Roussy Cancer Profiling study (ClinicalTrials.gov identifier: NCT04932525 ) underwent at least one liquid biopsy (FoundationOne Liquid CDx). Molecular reports were discussed within the Gustave Roussy Molecular Tumor Board (MTB). Potential CH alterations were observed, and patients referred to hematology consultation in the case of pathogenic mutations in JAK2, MPL, or MYD88, irrespective of the variant allele frequency (VAF), or in DNMT3A, TET2, ASXL1, IDH1, IDH2, SF3B1, or U2AF1 with VAF ≥ 10%, while also considering patient cancer-related prognosis. TP53 mutations were discussed case-by-case.

RESULTS

Between March and October 2021, 1,416 patients were included. One hundred ten patients (7.7%) carried at least one high-risk CH mutation: DNMT3A (n = 32), JAK2 (n = 28), TET2 (n = 19), ASXL1 (n = 18), SF3B1 (n = 5), IDH1 (n = 4), IDH2 (n = 3), MPL (n = 3), and U2AF1 (n = 2). The MTB advised for hematologic consultation in 45 patients. Overall, 9 patients of 18 actually addressed had confirmed hematologic malignancies that were occult in six patients: two patients had myelodysplastic syndrome, two essential thrombocythemia, one a marginal lymphoma, and one a Waldenström macroglobulinemia. The other three patients were already followed up in hematology.

CONCLUSION

The incidental findings of high-risk CH through liquid biopsy may trigger diagnostic hematologic tests and reveal an occult hematologic malignancy. Patients should have a multidisciplinary case-by-case evaluation.
A atuação da burocracia de médio escalão na pandemia de Covid-19
Authors: Guimarães Flávia Alves , Souza Letícia Godinho de , Costa Bruno Lazzarotti Diniz
Published: March 2023

Este artigo explora os efeitos da pandemia de Covid-19 na atuação da burocracia de médio escalão. Trata-se de uma pesquisa exploratória e de cunho qualitativo que adotou como estratégia de pesquisa o estudo de caso da burocracia responsável pela política de assistência social do município de Belo Horizonte (MG), no ano de 2020. A investigação foi conduzida por meio de pesquisa bibliográfica e documental, além de entrevistas semiestruturadas e aplicação de questionários. Captou-se a percepção do setor da burocracia estudado sobre as mudanças impressas nas dimensões intraorganizacionais da administração pública pela crise pandêmica. Foi possível notar que a crise afetou o regime de trabalho, os processos de tomada de decisão, as interações com outros atores e as habilidades demandadas para o desempenho das funções desses atores governamentais. A pesquisa evidenciou que a forma como a burocracia de médio escalão atuou ajuda a compreender o funcionamento do serviço e a resiliência da política pública no contexto de crise.
The present value of human life losses associated with COVID-19 and likely cost savings from vaccination in Kenya
Authors: Kirigia Joses , Mwabu Germano , Muthuri Rose Nabi Deborah Karimi
Published: March 2023

Background: The study estimates the total present value (TPVKENYA ) of human lives lost due to COVID-19, total indirect costs attributed to COVID-19 mortality, total direct costs of all COVID-19 cases, and projected cost savings due to COVID-19 vaccination as of 25 July 2022.

Methods: We used a human capital approach (HKA) model to estimate TPVKENYA . The indirect cost of COVID-19 (ICi=1,..,6)  for each of the six productive age groups equals the present value multiplied by the relevant employment-to-population ratio. The direct cost (DCi=1,..,4) for each of the four disease severity categories (asymptomatic, mild/moderate, severe, critical) is the product of the number of COVID-19 cases in a severity category and the average total direct cost per patient. The total direct cost saving equals the number of infections averted with vaccination multiplied by the average total direct cost per patient treated. The total indirect cost saving equals the number of COVID-19 deaths prevented with vaccination multiplied by the average total indirect cost per death.

Results: The cumulative 5670 human life losses had a TPVKENYA  of Int$268,408,687 and an average total present value of Int$47,338 per human life. A re-run of the HKA model with (a) discount rates of 5% and 10% reduced TPVKENYA by 16% and 39%, respectively; (b) Africa's highest life expectancy of 78.76 years and world's highest life expectancy of 88.17 years increased TPVKENYA by 79% and 129%, respectively; (c) excess mortality of 180,215 increased TPVKENYA by 3,078%. Total indirect and direct costs of COVID-19 were Int$36,833 per death and Int$1,648.2 per patient/case, respectively. The 30% target population's COVID-19 vaccination coverage may have saved Kenya a total cost of Int$ 1,400,945,809. 

Conclusions: The pandemic continues to erode Kenya's human health and economic development. However, scaling up COVID-19 vaccination coverage would save Kenya substantial direct and indirect costs.
Personality typologies of smokers and excessive drinkers: a cross-sectional survey of respondents in the BBC Lab UK Study
Authors: Perski Olga , Nikiel Astrid , Brown Jamie , Shahab Lion
Published: March 2023

Background: Several personality traits have been linked to addictive behaviours, including smoking and excessive drinking. We hypothesised that the combination of low conscientiousness, high extraversion and high neuroticism would be synergistically associated with smoking, excessive drinking and both behaviours combined.

Methods: Respondents aged 16+ years (N=363,454) were surveyed between 2009-2013 as part of the BBC Lab UK Study, with no restrictions on geographical location. Respondents provided information about sociodemographic characteristics, personality traits, and smoking and alcohol consumption. A series of multivariable logistic regression analyses were conducted.

Results: No significant three-way but significant two-way interactive effects were observed. The association of high extraversion with smoking was more pronounced in those with high (vs. low) conscientiousness (ORadj=1.51, 95% CI=1.46, 1.56, p<.001; ORadj=1.38, 95% CI=1.35, 1.42, p<.001). The association of high extraversion with excessive drinking was more pronounced in those with low (vs. high) conscientiousness (ORadj=1.70, 95% CI=1.67, 1.74, p<.001; ORadj=1.60, 95% CI=1.56, 1.63, p<.001). The association of high extraversion with both behaviours combined was more pronounced in those with high (vs. low) conscientiousness (ORadj=1.74, 95% CI=1.65, 1.83, p<.001; ORadj=1.62, 95% CI= 1.56, 1.68, p<.001). Results remained largely robust in sensitivity analyses.

Conclusions: In a large international survey, we identified two-way ‘personality typologies’ that are associated with greater odds of smoking, excessive drinking and both behaviours combined. The results may be useful for the tailoring of behaviour change interventions to at-risk individuals.
Uncertainty Quantification and Exploration for Reinforcement Learning
Authors: Zhu Yi , Dong Jing , Lam Henry
Published: March 2023

Quantify the uncertainty to decide and explore better

In statistical inference, large-sample behavior and confidence interval construction are fundamental in assessing the error and reliability of estimated quantities with respect to the data noises. In the paper “Uncertainty Quantification and Exploration for Reinforcement Learning”, Dong, Lam, and Zhu study the large sample behavior in the classic setting of reinforcement learning. They derive appropriate large-sample asymptotic distributions for the state-action value function (Q-value) and optimal value function estimations when data are collected from the underlying Markov chain. This allows one to evaluate the assertiveness of performances among different decisions. The tight uncertainty quantification also facilitates the development of a pure exploration policy by maximizing the worst-case relative discrepancy among the estimated Q-values (ratio of the mean squared difference to the variance). This exploration policy aims to collect informative training data to maximize the probability of learning the optimal reward collecting policy, and it achieves good empirical performance.
A post-structuralist feminist analysis of electronic fetal monitoring in labour
Authors: Melamed Anna
Published: March 2023

Constant electronic fetal monitoring has become a ubiquitous part of birth management in most high-income countries, both reflecting and creating the social context. This article uses a post-structuralist feminist critique to show that the use of the cardiotocograph in birth reinforces and reflects the logic of the separate sovereign self. This creates a rupture in the intrinsic relationality of the mother–fetus and the mother–midwife on a philosophical and physiological level. The cardiotocograph in labour privileges the medical model, constrains women through wires and the imperative to ‘keep the trace’, takes everyone’s attention and gives midwives tasks other than caring for the woman. It externalises the fetus and gives it selfhood separate from the mother, to the extent that it can seem like the machine is keeping the baby alive. This undermines women’s and midwives’ subjective knowledge, relegating women to organic containers. A reimagining of birth that centres relationality would start by acknowledging the nature of the self as semi-permeable and the being/doing, both/and nature of the mother–placenta–fetus in pregnancy and birth. Intermittent auscultation of the fetal heart in labour is better able to centre the mother–placenta–fetus relation and the midwife–mother relation.
Providing care to couples experiencing pregnancy loss
Authors: Latiff Hajah-Siti-Badariah , Saime Nur Syafiqah , Idris Deeni Rudita , Mohamad Siti Mazidah , Husaini Asmah , Matassan Nor Syahmun , Syam Azniah , Abdul-Mumin Khadizah H
Published: March 2023

This article discusses and evaluates the challenging and complex role of nurses and midwives in providing supportive care for couples after pregnancy loss. A planned pregnancy is usually a positive experience. However, some couples may experience pregnancy loss, which causes grief. While women may be severely affected, partners’ experiences are complicated by their role in caring for the grieving woman and their own experiences of grief. Nurses and midwives experience challenges when providing care, as pregnancy loss is emotional, entangling the joyous expectation of the start of life with the sorrow of a sudden end of life.
Keeping it locum-friendly
Authors: Lateefah Yakini
Published: March 2023

Yakini Lateefah gives the inside edge on welcoming a locum dental nurse to the practice.
A day in the life
Authors: Hartley Rachael
Published: March 2023

Rachael Hartley walks us through a day in the life of an orthodontic therapist.
The bridge between
Authors: Hylton Preetee
Published: March 2023

Preetee Hylton sits down with Charlotte Astley to discuss her dental nursing career, and what the future may hold!
Two months as the president!
Authors: Worthington Deborah
Published: March 2023

President of the .BADN Debra Worthington gives an update on her exciting new role.
Alleviating the oxidative stress in Japanese quails fed L- carnitine and creatine monohydrate through impacts on productive performance, ileal microflora, digestibility and redox system
Authors:   Department of Animal Production Techniques, Al-Musaib Technical College, Al-Furat Al-Awsat Technical University, Babylon 54003, Iraq, Imad Abdulsahib Al-Shammari Karrar
Published: March 2023

This study was aimed to investigate the effects of L-carnitine (Car), creatine monohydrate (CrM) and their combination (CarCrM) as dietary antioxidants materials on productive performance, digestibility, ileal eubiosis, blood chemistry and redox system of stressed quails challenged by lead acetate (LA) in drinking water. In total, 600 quails were assigned into 5 treatments with 4 replications each and 30 chicks per replication from 1 until 42 days old. The treatments involved control (T1), stressed treatment (adding 2.5 ppm of LA in drinking water only; T2) and treatments of adding 500 mg/kg Car+LA (T3), 500 mg/kg CrM+LA (T4) and CarCrM (250 mg/kg Car plus 250 mg/kg CrM)+LA (T5). A completely randomized design was followed to analyze treatment influences on variables. In comparison to T2, the results showed that T5 and T4 had equivalent positive influence followed by T3 to increase (p≤0.05) body weight, feed intake, survivability, carcass yield and digestibility accompanied with increase lactic acid bacteria and reduced total coliform, E.coli in ileum. Also, increased levels (p≤0.05) of glutathione peroxidase, superoxide dismutase, catalase and glutathione in serum and ferric-reducing ability of plasma were obtained by T5 followed by T4. Moreover, T5 and T4 achieved low values (p≤0.05) of feed efficiency and serum lipid hydroperoxide, malondialdehyde, cortisol, aspartate transaminase, alanine aminotransferase, alkaline phosphatase,gamma-glutamyl transferase, creatine kinase and creatinine. The results confirm that dietary CarCrM or CrM mitigated stress and reinforced antioxidant pool which was reflected by supported productive and physiological aspects of birds. Dietary Car seemed less powerful effect than CarCrM and CrM but without negative influence compared with stressed treatment.
An overview of the antimicrobial activity of some essential oils against fish pathogenic bacteria
Authors:   Laboratory of Aquatic Animal Medicine, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, 28644, Republic of Korea (South Korea), Wickramanayake M.V.K.S. , Kumarage P.M. ,   Laboratory of Aquatic Animal Medicine, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, 28644, Republic of Korea (South Korea), Majeed Sana ,   Laboratory of Aquatic Animal Medicine, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, 28644, Republic of Korea (South Korea), Heo G.J. ,   Laboratory of Aquatic Animal Medicine, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, 28644, Republic of Korea (South Korea)
Published: March 2023

Plant-derived essential oils as an alternative treatment method for antimicrobial-resistant bacteria have gained interest over the past few decades, particularly in the food and aquaculture industry. Essential oil is considered as a natural, cost-effective compound with a minimum impact on the environment. Studies have suggested the use of essential oils in the treatment and/or prevention of infectious diseases in fish may be a cost-effective alternative to synthetic antimicrobials. In addition to that,hundreds of different chemical profiles have been identified in essential oils. Particularly, in the same essential oil. In contrast to the synthetic antimicrobials that have unique chemical compositions between every product belonging to the same drug, the same essential oil may not perform unique antimicrobial activity every time. Therefore, more studies and concluded data are required for the effective usage of essential oils as an alternative to antimicrobial agents. In this review, we have summarized the studies about the several active essential oils that are known and tested against fish pathogenic bacteria because of their antimicrobial properties
A preliminary study of the effects of enrichment tools on stereotypic behavior in captive Sun Bear (Helarctos malayanus)
Authors:   Veterinary Technology Program, Faculty of Science and Technology, Nakhon Ratchasima Rajabhat University, Nakhon Ratchasima 30000, Thailand, Huo Xin , Ongpimai Khwanchanok ,   Veterinary Technology Program, Faculty of Science and Technology, Nakhon Ratchasima Rajabhat University, Nakhon Ratchasima 30000, Thailand, Kamwongpanao Supattra ,   Veterinary Technology Program, Faculty of Science and Technology, Nakhon Ratchasima Rajabhat University, Nakhon Ratchasima 30000, Thailand, Uttaraviset Tanat ,   Nakhon Ratchasima Zoo, 111 M. 1, Ratchasima Pak Tongchai Road, Chaimongkol, Muang, Nakhon Ratchasima 30000, Thailand, Changphet Wirongrong ,   Nakhon Ratchasima Zoo, 111 M. 1, Ratchasima Pak Tongchai Road, Chaimongkol, Muang, Nakhon Ratchasima 30000, Thailand, Lekthong Pariyakorn ,   Nakhonratchasima Zoo, 111 M. 1, Ratchasima Pak Tongchai Road, Chaimongkol, Muang, Nakhon Ratchasima 30000, Thailand
Published: March 2023

The stereotypic behaviors are common in captive bear. The objectives of study were to investigate 1) the effects of new enrichment tools on frequency of hand sucking/licking (HS) and pacing in captive sun bear; 2) the response of sun bear to each new enrichment tool. The data collection was divided into 5 parts: 1) before using enrichment 2) using puzzle feeder (PF) 3) using bamboo cradle) (BC) 4) using container (C) and 5) without using any new enrichment tool. The results showed that the frequency of HS in sun bear was not significantly affected by new enrichment tools (P>0.05). The lowest frequency of pacing was found after using new enrichment tools (P<0.001). However, it was not significantly different between before and after using new enrichment tools. The frequency of pacing using PF was lower than that of using BC and C. The highest duration of response to the new enrichment tool was in PF (P=0.002). In conclusion, using new enrichment tools could not significantly reduce the frequency of hand-sucking/licking in captive sun bear. However, it could stimuli the frequency of pacing in sun bear. The captive sun bear would be more interested in the edible enrichment tool, which could reduce the frequency of pacing compared with using other types of enrichment tools. Therefore, it is necessary to conduct a long-term experimental enrichment tool using program in the future study.
Effects of L-serine administration on meat quality, characteristics and mineral content of tibia bone in heat-stressed broiler
Authors:   Department of Physiology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria 810222, Nigeria, Ogbuagu Ngozi Ejum , Ayo Joseph Olusegun ,   Department of Physiology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria 810222, Nigeria
Published: March 2023

in heat-stressed broiler chickens. One hundred and twenty broiler chicks were allocated into four groups of 30 each. Group A (feed restriction), Group B (feed restriction + L-serine), Group C (ad libitum) and Group D (ad libitum + L-serine). Feed restriction (20%) was implemented on days 7–14, and L-serine (200 mg/kg) was provided orally from days 1–14. Seven broiler chickens were slaughtered from each group at 35 days old to determine meat drip loss, cooking loss and pH; and tibia bone weight, length, diameter, weight/length index, robusticity index, strength and proximate analysis. Serum samples were harvested for the determination of calcium and phosphorus concentrations. Temperature-humidity index in the pen (28.72 - 32.90) was above the thermoneutral zone indicating heat stress. The drip loss and cooking loss were lower in FR + L-serine and AL + L-serine groups compared to the controls. The tibia bone weight, length, weight/length index and breaking force were higher (P < 0.05) in FR + L-serine and AL + L-serine groups compared to the controls. The percentage composition of ash, calcium and phosphorus was relatively high in L-serine-administered groups. In conclusion, L-serine improved meat quality and tibia bone characteristics in broiler chickens exposed to heat stress