bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a novel, entirely herbal-based mouthwash effective against common oral bacteria and SARS-CoV-2
Authors: Bencze Bálint , Temesfői Viktória , Das Sourav , Papp Henrietta , Kaltenecker Péter , Kuczmog Anett , Jakab Ferenc , Kocsis Béla , Kőszegi Tamás
Published: May 2023

Background

Parallel to the growth of the oral healthcare market, there is a constantly increasing demand for natural products as well. Many customers prefer products that contain fewer toxic agents, therefore providing an environmentally friendly solution with the benefit of smaller risk to the user. Medieval and early modern medicinal knowledge might be useful when looking for natural, herbal-based components to develop modern products. Along with these considerations we created, tested, and compared an entirely natural mouthwash, named Herba Dei.

Methods

The manufacturing procedure was standardized, and the created tincture was evaluated by GC/MS analysis for active compounds, experimentally tested in cell-based cytotoxicity, salivary protein integrity, cell-free antioxidant activity, anti-bacterial and anti-viral assays, and compared with three market-leading mouthwashes.

Results

Our tincture did not show significant damage in the cytotoxicity assays to keratinocyte and Vero E6 cells and did not disrupt the low molecular weight salivary proteins. Its radical scavenging capacity surpassed that of two tested, partly natural, and synthetic mouthwashes, while its antibacterial activity was comparable to the tested products, or higher in the bacterial aerobic respiratory assay. The active compounds responsible for the effects include naturally occurring phenylpropanoids, terpenes, and terpenoids. Our mouthwash proved to be effective in vitro in lowering the copy number of SARS-CoV-2 in circumstances mimicking the salivary environment.

Conclusions

The developed product might be a useful tool to impede the transmission and spread of SARS-CoV-2 in interpersonal contact and aerosol-generating conditions. Our mouthwash can help reduce the oral bacterial flora and has an antioxidant activity that facilitates wound healing and prevents adverse effects of smoke in the oral cavity.
Guidance for management competency identification and development in the health context: a systematic scoping review
Authors: Kakemam Edris , Liang Zhanming
Published: May 2023

Background

Using management competency-based frameworks to guide developing and delivering training and formal education to managers has been increasingly recognized as a key strategy in building management capacity. Hence, interest in identifying and confirming the competency requirements in various contexts have been witnessed. Therefore, learnings from how competency studies were designed and conducted, how competencies were identified, and strategies in ensuring success in competency identification are of great value to researchers planning and conducting competency studies in their own country.

Methods

A scoping review was conducted guided by the Arksey and O’Malley framework and reported according to the PRISMA Extension for Scoping Reviews (PRISMA-ScR). All papers that published empirical studies aiming at identifying and assessing manager’s competencies at the peer-reviewed journals were identified from Web of sciences, PubMed, Scopus and Emerald Management between 2000 and 2021. In order to maximize learning, studies focusing on health and non-health sectors are all included.

Results

In total, 186 studies were included in the review including slightly more than half of the studies conducted in health sector (54.5%). 60% of the studies focused on mid to senior level managers. Surveys and Interviews were the two most commonly used methods either solely or as part of the mix-method in the studies. Half of the studies used mixed methods approach (51.1%). Large proportion of the papers failed to include all information that is necessary to contribute to learning and improvement in future study design. Based on the results of the scoping review a four steps framework was developed that can guide designing and implementing management competency studies in specific country vs. sector context and to ensure benefits of the studies are maximised.

Conclusion

The review confirmed the increasing trend in investing in management competency studies and that the management competency identification and development process varied substantially, in the choice of methods and processes. The identification of missing information in majority of the published studies calls for the development of more rigorous guidelines for the peer-review process of journal publications. The proposed framework of improving the quality and impact of the future management competency study provides clear guidance to management competency identification and development that promotes the functional alignment of methods and strategies with intended uses and contexts.
Identification and validation of immune-related biomarkers and potential regulators and therapeutic targets for diabetic kidney disease
Authors: Chen Shengnan , Li Bo , Chen Lei , Jiang Hongli
Published: May 2023

Background

Diabetic kidney disease (DKD) is a major complication of diabetes and the leading cause of end-stage renal disease worldwide. Renal inflammation and infiltration of immune cells contribute to the development and progression of DKD. Thus, the aim of the present study was to identify and validate immune-related biomarkers and analyze potential regulators including transcription factors (TFs), microRNAs (miRNAs), and drugs for DKD.

Methods

Immune-related genes from the ImmPort database and glomeruli samples from GSE1009 and GSE30528 were used to identify differentially expressed immune-related genes (DEIRGs) of DKD. The expression level and clinical correlation analyses of DEIRGs were verified in the Nephroseq database. Murine podocytes were cultured to construct the high glucose-induced podocyte injury model. The reliability of the bioinformatics analysis was experimentally validated by RT-qPCR in podocytes. Networks among DEIRGs, regulators, and drugs were constructed to predict potential regulatory mechanisms for DKD.

Results

DKD-associated DEIRGs were identified. CCL19 and IL7R were significantly upregulated in the DKD group and negatively correlated with glomerular filtration rate (GFR). GHR, FGF1, FYN, VEGFA, F2R, TGFBR3, PTGDS, FGF9, and SEMA5A were significantly decreased in the DKD group and positively correlated with GFR. RT-qPCR showed that the relative mRNA expression levels of GHR, FGF1, FYN, TGFBR3, PTGDS, FGF9, and SEMA5A were significantly down-regulated in the high glucose-induced podocyte injury group. The enriched regulators for DEIRGs included 110 miRNAs and 8 TFs. The abnormal expression of DEIRGs could be regulated by 16 established drugs.

Conclusions

This study identified immune-related biomarkers, regulators, and drugs of DKD. The findings of the present study provide novel insights into immune-related diagnosis and treatment of DKD.
Plasmodium falciparum kelch13 polymorphisms identified after treatment failure with artemisinin-based combination therapy in Niger
Authors: Arzika Ibrahima Issa , Lobo Neil F. , Lamine Mahaman Moustapha , Tidjani Ilagouma Amadou , Sandrine Houzé , Sarrasin-Hubert Véronique , Mahamadou Aboubacar , Adehossi Eric , Sarr Demba , Mahmud Ousman , Maman Laminou Ibrahim
Published: May 2023

Background

Artemisinin-based combination therapy (ACT) is the most effective treatment for malaria, and has significantly reduced morbimortality. Polymorphisms associated with the Plasmodium falciparum Kelch gene (Pfkelch13) have been associated with delayed parasite clearance even with ACT treatment.

Methods

The Pfkelch13 gene was sequenced from P. falciparum infected patients (n = 159) with uncomplicated malaria in Niger. An adequate clinical and parasitological response (ACPR) was reported in 155 patients. Four (n = 4) patients had treatment failure (TF) that were not reinfections—two of which had late parasitological failures (LPF) and two had late clinical failures (LCF).

Results

Thirteen single nucleotide polymorphisms (SNPs) were identified of which seven were non-synonymous (C469R, T508S, R515T, A578S, I465V, I437V, F506L,), and three were synonymous (P443P, P715P, L514L). Three SNP (C469R, F506L, P715P) were present before ACT treatment, while seven mutations (C469R, T508S, R515T, L514L, P443P, I437V, I465V) were selected by artemether/lumefantrine (AL)—five of which were non-synonymous (C469R, T508S, R515T, I437V, I465V). Artesunate/amodiaquine (ASAQ) has selected any mutation. One sample presented three cumulatively non-synonymous SNPs—C469R, T508S, R515T.

Conclusions

This study demonstrates intra-host selection of Pfkelch13 gene by AL. The study highlights the importance of LCF and LPF parasites in the selection of resistance to ACT. Further studies using gene editing are required to confirm the potential implication of resistance to ACT with the most common R515T and T508S mutations. It would also be important to elucidate the role of cumulative mutations.
Impact assessment of the Centre for Research Excellence in Stroke Rehabilitation and Brain Recovery
Authors: Ramanathan Shanthi , Lynch Elizabeth , Bernhardt Julie , Nilsson Michael , Cadilhac Dominique A. , Carey Leeanne , Middleton Sandy , Chamberlain Jan , Walker Frederick Rohan , Reeves Penny , Searles Andrew
Published: May 2023

Background

Research impact is an emerging measure of research achievement alongside traditional academic outputs such as publications. We present the results of applying the Framework to Assess the Impact from Translational health research (FAIT) to the Centre for Research Excellence (CRE) in Stroke Rehabilitation and Brain Recovery (CRE-Stroke, 2014–2019) and report on the feasibility and lessons from the application of FAIT to a CRE rather than a discrete research project.

Methods

Data were gathered via online surveys, in-depth interviews, document analysis and review of relevant websites/databases to report on the three major FAIT methods: the modified Payback Framework, an assessment of costs against monetized consequences, and a narrative account of the impact generated from CRE-Stroke activities. FAIT was applied during the last 4 years of CRE-Stroke operation.

Results

With an economic investment of AU$ 3.9 million over 5 years, CRE-Stroke delivered a return on investment that included AU$ 18.8 million in leveraged grants, fellowships and consultancies. Collectively, CRE-Stroke members produced 354 publications that were accessed 470,000 times and cited over 7220 times. CRE-Stroke supported 26 PhDs, 39 postdocs and seven novice clinician researchers. There were 59 capacity-building events benefiting 744 individuals including policy-makers and consumers. CRE-Stroke created research infrastructure (including a research register of stroke survivors and a brain biobank), and its global leadership produced international consensus recommendations to influence the stroke research landscape worldwide. Members contributed to the Australian Living Stroke Guidelines: four researchers’ outputs were directly referenced. Based only on the consequences that could be monetized, CRE-Stroke returned AU$ 4.82 for every dollar invested in the CRE.

Conclusion

This case example in the developing field of impact assessment illustrates how researchers can use evidence to demonstrate and report the impact of and returns on research investment. The prospective application of FAIT by a dedicated research impact team demonstrated impact in broad categories of knowledge-gain, capacity-building, new infrastructure, input to policy and economic benefits. The methods can be used by other research teams to provide comprehensive evidence to governments and other research funders about what has been generated from their research investment but requires dedicated resources to complete.
Examining respect, autonomy, and mistreatment in childbirth in the US: do provider type and place of birth matter?
Authors: Niles P. Mimi , Baumont Monique , Malhotra Nisha , Stoll Kathrin , Strauss Nan , Lyndon Audrey , Vedam Saraswathi
Published: May 2023

Background

Analyses of factors that determine quality of perinatal care consistently rely on clinical markers, while failing to assess experiential outcomes. Understanding how model of care and birth setting influence experiences of respect, autonomy, and decision making, is essential for comprehensive assessment of quality.

Methods

We examined responses (n = 1771) to an online cross-sectional national survey capturing experiences of perinatal care in the United States. We used validated patient-oriented measures and scales to assess four domains of experience: (1) decision-making, (2) respect, (3) mistreatment, and (4) time spent during visits. We categorized the provider type and birth setting into three groups: midwife at community birth, midwife at hospital-birth, and physician at hospital-birth. For each group, we used multivariate logistic regression, adjusted for demographic and clinical characteristics, to estimate the odds of experiential outcomes in all the four domains.

Results

Compared to those cared for by physicians in hospitals, individuals cared for by midwives in community settings had more than five times the odds of experiencing higher autonomy (aOR: 5.22, 95% CI: 3.65–7.45), higher respect (aOR: 5.39, 95% CI: 3.72–7.82) and lower odds of mistreatment (aOR: 0.16, 95% CI: 0.10–0.26). We found significant differences across birth settings: participants cared for by midwives in the community settings had significantly better experiential outcomes than those in the hospital settings: high- autonomy (aOR: 2.97, 95% CI: 2.66–4.27), respect (aOR: 4.15, 95% CI: 2.81–6.14), mistreatment (aOR: 0.20, 95% CI: 0.11–0.34), time spent (aOR: 8.06, 95% CI: 4.26–15.28).

Conclusion

Participants reported better experiential outcomes when cared for by midwives than by physicians. And for those receiving midwifery care, the quality of experiential outcomes was significantly higher in community settings than in hospital settings. Care settings matter and structures of hospital-based care may impair implementation of the person-centered midwifery care model.
Peripheral blood lymphocytes influence human papillomavirus infection and clearance: a retrospective cohort study
Authors: Li Ye , Feng Yebin , Chen Yanlin , Lin Wenyu , Gao Hangjing , Chen Ming , Osafo Kelvin Stefan , Mao Xiaodan , Kang Yafang , Huang Leyi , Liu Dabin , Xu Shuxia , Huang Lixiang , Dong Binhua , Sun Pengming
Published: May 2023

Background

There is a close correlation between HPV infection and systemic immune status. The purpose of this study was to determine which lymphocytes in peripheral blood influence human papillomavirus (HPV) infection and to identify whether peripheral blood lymphocyte (PBL) subsets could be used as biomarkers to predict HPV clearance in the short term.

Methods

This study involved 716 women undergoing colposcopy from 2019 to 2021. Logistic and Cox regression were used to analyze the association of PBLs with HPV infection and clearance. Using Cox regression, bidirectional stepwise regression and the Akaike information criterion (AIC), lymphocyte prediction models were developed, with the C-index assessing performance. ROC analysis determined optimal cutoff values, and their accuracy for HPV clearance risk stratification was evaluated via Kaplan‒Meier and time-dependent ROC. Bootstrap resampling validated the model and cutoff values.

Results

Lower CD4 + T cells were associated with a higher risk of HPV, high-risk HPV, HPV18 and HPV52 infections, with corresponding ORs (95% CI) of 1.58 (1.16–2.15), 1.71 (1.23–2.36), 2.37 (1.12–5.02), and 3.67 (1.78–7.54), respectively. PBL subsets mainly affect the natural clearance of HPV, but their impact on postoperative HPV outcomes is not significant (P > 0.05). Lower T-cell and CD8 + T-cell counts, as well as a higher NK cell count, are unfavorable factors for natural HPV clearance (P < 0.05). The optimal cutoff values determined by the PBL prognostic model (T-cell percentage: 67.39%, NK cell percentage: 22.65%, CD8 + T-cell model risk score: 0.95) can effectively divide the population into high-risk and low-risk groups, accurately predicting the natural clearance of HPV. After internal validation with bootstrap resampling, the above conclusions still hold.

Conclusions

CD4 + T cells were important determinants of HPV infection. T cells, NK cells, and CD8 + T cells can serve as potential biomarkers for predicting natural HPV clearance, which can aid in patient risk stratification, individualized treatment, and follow-up management.
Drainless robot-assisted minimally invasive oesophagectomy—randomized controlled trial (RESPECT)
Authors: Müssle B. , Kirchberg J. , Buck N. , Radulova-Mauersberger O. , Stange D. , Richter T. , Müller-Stich B. , Klotz R. , Larmann J. , Korn S. , Klimova A. , Grählert X. , Trips E. , Weitz J. , Welsch T.
Published: May 2023

Background

The purpose of this randomized trial is to evaluate the early removal of postoperative drains after robot-assisted minimally invasive oesophagectomy (RAMIE). Evidence is lacking about feasibility, associated pain, recovery, and morbidity.

Methods/design

This is a randomized controlled multicentric trial involving 72 patients undergoing RAMIE. Patients will be allocated into two groups. The “intervention” group consists of 36 patients. In this group, abdominal and chest drains are removed 3 h after the end of surgery in the absence of contraindications. The control group consists of 36 patients with conventional chest drain management. These drains are removed during the further postoperative course according to a standard algorithm. The primary objective is to investigate whether postoperative pain measured by NRS on the second postoperative day can be significantly reduced in the intervention group. Secondary endpoints are the intensity of pain during the first week, analgesic use, number of postoperative chest X-ray and CT scans, interventions, postoperative mobilization (steps per day as measured with an activity tracker), postoperative morbidity and mortality.

Discussion

Until now, there have been no trials investigating different intraoperative chest drain strategies in patients undergoing RAMIE for oesophageal cancer with regard to perioperative complications until discharge. Minimally invasive approaches combined with enhanced recovery after surgery (ERAS) protocols lower morbidity but still include the insertion of chest drains. Reduction and early removal have been proposed after pulmonary surgery but not after RAMIE. The study concept is based on our own experience and the promising current results of the RAMIE procedure. Therefore, the presented randomized controlled trial will provide statistical evidence of the effectiveness and feasibility of the “drainless” RAMIE.

Trial registration

ClinicalTrials.gov NCT05553795. Registered on 23 September 2022.
Single-nucleus RNA sequencing of human pancreatic islets identifies novel gene sets and distinguishes β-cell subpopulations with dynamic transcriptome profiles
Authors: Kang Randy B. , Li Yansui , Rosselot Carolina , Zhang Tuo , Siddiq Mustafa , Rajbhandari Prashant , Stewart Andrew F. , Scott Donald K. , Garcia-Ocana Adolfo , Lu Geming
Published: May 2023

Background

Single-cell RNA sequencing (scRNA-seq) provides valuable insights into human islet cell types and their corresponding stable gene expression profiles. However, this approach requires cell dissociation that complicates its utility in vivo. On the other hand, single-nucleus RNA sequencing (snRNA-seq) has compatibility with frozen samples, elimination of dissociation-induced transcriptional stress responses, and affords enhanced information from intronic sequences that can be leveraged to identify pre-mRNA transcripts.

Methods

We obtained nuclear preparations from fresh human islet cells and generated snRNA-seq datasets. We compared these datasets to scRNA-seq output obtained from human islet cells from the same donor. We employed snRNA-seq to obtain the transcriptomic profile of human islets engrafted in immunodeficient mice. In both analyses, we included the intronic reads in the snRNA-seq data with the GRCh38-2020-A library.

Results

First, snRNA-seq analysis shows that the top four differentially and selectively expressed genes in human islet endocrine cells in vitro and in vivo are not the canonical genes but a new set of non-canonical gene markers including ZNF385D, TRPM3, LRFN2, PLUT (β-cells); PTPRT, FAP, PDK4, LOXL4 (α-cells); LRFN5, ADARB2, ERBB4, KCNT2 (δ-cells); and CACNA2D3, THSD7A, CNTNAP5, RBFOX3 (γ-cells). Second, by integrating information from scRNA-seq and snRNA-seq of human islet cells, we distinguish three β-cell sub-clusters: an INS pre-mRNA cluster (β3), an intermediate INS mRNA cluster (β2), and an INS mRNA-rich cluster (β1). These display distinct gene expression patterns representing different biological dynamic states both in vitro and in vivo. Interestingly, the INS mRNA-rich cluster (β1) becomes the predominant sub-cluster in vivo.

Conclusions

In summary, snRNA-seq and pre-mRNA analysis of human islet cells can accurately identify human islet cell populations, subpopulations, and their dynamic transcriptome profile in vivo.
Spatial transcriptomic analysis of Sonic hedgehog medulloblastoma identifies that the loss of heterogeneity and promotion of differentiation underlies the response to CDK4/6 inhibition
Authors: Vo Tuan , Balderson Brad , Jones Kahli , Ni Guiyan , Crawford Joanna , Millar Amanda , Tolson Elissa , Singleton Matthew , Kojic Marija , Robertson Thomas , Walters Shaun , Mulay Onkar , Bhuva Dharmesh D. , Davis Melissa J. , Wainwright Brandon J. , Nguyen Quan , Genovesi Laura A.
Published: May 2023

Background

Medulloblastoma (MB) is a malignant tumour of the cerebellum which can be classified into four major subgroups based on gene expression and genomic features. Single-cell transcriptome studies have defined the cellular states underlying each MB subgroup; however, the spatial organisation of these diverse cell states and how this impacts response to therapy remains to be determined.

Methods

Here, we used spatially resolved transcriptomics to define the cellular diversity within a sonic hedgehog (SHH) patient-derived model of MB and show that cells specific to a transcriptional state or spatial location are pivotal for CDK4/6 inhibitor, Palbociclib, treatment response. We integrated spatial gene expression with histological annotation and single-cell gene expression data from MB, developing an analysis strategy to spatially map cell type responses within the hybrid system of human and mouse cells and their interface within an intact brain tumour section.

Results

We distinguish neoplastic and non-neoplastic cells within tumours and from the surrounding cerebellar tissue, further refining pathological annotation. We identify a regional response to Palbociclib, with reduced proliferation and induced neuronal differentiation in both treated tumours. Additionally, we resolve at a cellular resolution a distinct tumour interface where the tumour contacts neighbouring mouse brain tissue consisting of abundant astrocytes and microglia and continues to proliferate despite Palbociclib treatment.

Conclusions

Our data highlight the power of using spatial transcriptomics to characterise the response of a tumour to a targeted therapy and provide further insights into the molecular and cellular basis underlying the response and resistance to CDK4/6 inhibitors in SHH MB.
Expression of Myomaker and Myomerger in myofibers causes muscle pathology
Authors: Witcher Phillip C. , Sun Chengyi , Millay Douglas P.
Published: May 2023

Background

Skeletal muscle development and regeneration depend on cellular fusion of myogenic progenitors to generate multinucleated myofibers. These progenitors utilize two muscle-specific fusogens, Myomaker and Myomerger, which function by remodeling cell membranes to fuse to each other or to existing myofibers. Myomaker and Myomerger expression is restricted to differentiating progenitor cells as they are not detected in adult myofibers. However, Myomaker remains expressed in myofibers from mice with muscular dystrophy. Ablation of Myomaker from dystrophic myofibers results in reduced membrane damage, leading to a model where persistent fusogen expression in myofibers, in contrast to myoblasts, is harmful.

Methods

Dox-inducible transgenic mice were developed to ectopically express Myomaker or Myomerger in the myofiber compartment of skeletal muscle. We quantified indices of myofiber membrane damage, such as serum creatine kinase and IgM+ myofibers, and assessed general muscle histology, including central nucleation, myofiber size, and fibrosis.

Results

Myomaker or Myomerger expression in myofibers independently caused membrane damage at acute time points. This damage led to muscle pathology, manifesting with centrally nucleated myofibers and muscle atrophy. Dual expression of both Myomaker and Myomerger in myofibers exacerbated several aspects of muscle pathology compared to expression of either fusogen by itself.

Conclusions

These data reveal that while myofibers can tolerate some level of Myomaker and Myomerger, expression of a single fusogen above a threshold or co-expression of both fusogens is damaging to myofibers. These results explain the paradigm that their expression in myofibers can have deleterious consequences in muscle pathologies and highlight the need for their highly restricted expression during myogenesis and fusion.
A wound-friendly antibacterial hyaluronic acid dressing with on-demand removability for infected wound healing
Authors: Hu Datao , Wen Jinpeng , Zhao Xinxin , Liu Kailai , Zhang Yuchen , Bu Yizhuo , Wang Ke
Published: May 2023

Background

Antibacterial activity and on-demand removability are key characteristics governing the effectiveness of clinic wound dressing. However, the excellent tissue adhesion of new dressings is often overemphasized without a detailed discussion of dressing replacement. Besides, the inherent antibacterial ability of dressings is beneficial for promoting the healing of infected wound. Therefore, we rationally design an injectable antibacterial wound dressing with on-demand removability to accelerate infected wound healing.

Method

We design this wound dressing with a simple and feasible method based on the electrostatic self-assembly of hyaluronic acid and ε-polylysine. We investigated the efficacy of this dressing in terms of its microtopography, rheology, self-healing performance, adhesive ability, antimicrobial, hemostatic, on-demand removal properties, and wound healing promotion through various tests.

Results

The prepared dressing possesses injectability, self-healing ability and antibacterial activity, showing NaCl-triggered on-demand dissolution due to the disruption of electrostatic interactions. When used as dressings for healing full-thickness wounds, it could effectively accelerate wound healing by killing bacteria, downregulating inflammation, promoting collagen deposition, enhancing keratinocyte migration and angiogenesis due to its excellent adhesion ability, favorable hemostatic property, and potent antibacterial performance.

Conclusion

All results indicate that this is a simple and practical dressing for clinical application. This strategy provides a novel idea for developing on-demand removal dressings with antibacterial and injectable properties.
The aggregate and sectoral time-varying market efficiency during crisis periods in Turkey: a comparative analysis with COVID-19 outbreak and the global financial crisis
Authors: Erer Deniz , Erer Elif , Güngör Selim
Published: May 2023

This study aims to examine the time-varying efficiency of the Turkish stock market’s major stock index and eight sectoral indices, including the industrial, financial, service, information technology, basic metals, tourism, real estate investment, and chemical petrol plastic, during the COVID-19 outbreak and the global financial crisis (GFC) within the framework of the adaptive market hypothesis. This study employs multifractal detrended fluctuation analysis to illustrate these sectors’ multifractality and short- and long-term dependence. The results show that all sectoral returns have greater persistence during the COVID-19 outbreak than during the GFC. Second, the real estate and information technology industries had the lowest levels of efficiency during the GFC and the COVID-19 outbreak. Lastly, the fat-tailed distribution has a greater effect on multifractality in these industries. Our results validate the conclusions of the adaptive market hypothesis, according to which arbitrage opportunities vary over time, and contribute to policy formulation for future outbreak-induced economic crises.
Non-linear dose response of DNA double strand breaks in response to chronic low dose radiation in individuals from high level natural radiation areas of Kerala coast
Authors: Jain Vinay , Saini Divyalakshmi , Soren D. C. , Kumar V. Anil , Vivek Kumar P. R. , Koya P. K. M. , Jaikrishan G. , Das Birajalaxmi
Published: May 2023

Background

The human population living in high level natural radiation areas (HLNRAs) of Kerala coast provide unique opportunities to study the biological effects of low dose and low dose rate ionizing radiation below 100 mGy. The level of radiation in this area varies from < 1.0 to 45 mGy/year. The areas with ≤ 1.50 mGy/year are considered as normal level natural radiation areas (NLNRA) and > 1.50 mGy/year, as high level natural radiation areas (HLNRA). The present study evaluated dose response relationship between DNA double strand breaks (DSBs) and background radiation dose in individuals residing in Kerala coast. Venous blood samples were collected from 200 individuals belonging to NLNRA (n = 50) and four dose groups of HLNRA; 1.51-5.0 mGy/year (n = 50), 5.01-10.0 mGy/year (n = 30), 10.01-15.0 mGy/year (n = 33), > 15.0 mGy/year (n = 37) with written informed consent. The mean dose of NLNRA and four HLNRA dose groups studied are 1.21 ± 0.21 (range: 0.57–1.49), 3.02 ± 0.95 (range: 1.57–4.93), 7.43 ± 1.48 (range: 5.01–9.75), 12.22 ± 1.47 (range: 10.21–14.99), 21.64 ± 6.28 (range: 15.26–39.88) mGy/year, respectively. DNA DSBs were quantified using γH2AX as a marker, where foci were counted per cell using fluorescence microscopy.

Results

Our results revealed that the frequency of γH2AX foci per cell was 0.090 ± 0.051 and 0.096 ± 0.051, respectively in NLNRA and HLNRA individuals, which were not significantly different (t198 = 0.33; P = 0.739). The frequency of γH2AX foci was observed to be 0.090 ± 0.051, 0.096 ± 0.051, 0.076 ± 0.036, 0.087 ± 0.042, 0.108 ± 0.046 per cell, respectively in different dose groups of ≤ 1.50, 1.51-5.0, 5.01-10.0, 10.01-15.0, > 15.0mGy/year (ANOVA, F4,195 = 2.18, P = 0.072) and suggested non-linearity in dose response. The frequency of γH2AX foci was observed to be 0.098 ± 0.042, 0.078 ± 0.037, 0.084 ± 0.042, 0.099 ± 0.058, 0.097 ± 0.06 and 0.114 ± 0.033 per cell in the age groups of ≤ 29, 30–34, 35–39, 40–44, 45–49 and ≥ 50 years, respectively (ANOVA, F5,194 = 2.17, P = 0.059), which suggested marginal influence of age on the baseline of DSBs. Personal habits such as smoking (No v/s Yes: 0.092 ± 0.047 v/s 0.093 ± 0.048, t198 = 0.13; P = 0.895) and drinking alcohol (No v/s Yes: 0.096 ± 0.052 v/s 0.091 ± 0.045, t198 = 0.62; P = 0.538) did not show any influence on DSBs in the population.

Conclusion

The present study did not show any increase in DSBs in different dose groups of HLNRA compared to NLNRA, however, it suggested a non-linear dose response between DNA DSBs and chronic low dose radiation.
A qualitative study to identify thematic areas for HIV related patient-reported outcome measures (PROM) and patient-reported experience measures (PREM)
Authors: Lohiniva Anna-Leena , Isosomppi Sanna , Pasanen Sini , Sutinen Jussi
Published: May 2023

Background

The use of patient-reported outcome measures (PROM) and patient-reported experience measures (PREM) provide health providers with valuable feedback on how to improve clinical care and patient outcomes. This paper describes a qualitative study that was conducted to learn about factors influencing the well-being of people living with HIV (PLHIV) in Finland. The findings will be used to develop themes for HIV-specific PROM and PREM questions.

Methods

PROMs and PREMs were developed by the Finnish Institute for Health (THL) as a part of a project to develop a national quality-of-care registry for HIV. The study aimed to identify issues and concerns among people living with HIV (PLHIV) that influence their well-being (PROMs) and their experiences in the healthcare system (PREMs). The data were collected through face-to-face in-depth interviews and focus group discussions based on open-ended and semi-structured questions. The data were analyzed using thematic analysis.

Results

The assessment identified the following PROMs of concern: psychological well-being, concerns about stigma, physical health, social well-being, sexual well-being, medication uptake, managing other medications with antiretrovirals (ARVs), and growing old. The assessment identified the following PREMs: helping patients understand their own health status, proving an opportunity for patients to discuss physical health, psychological and sexual well-being, supporting the uptake of ARVs, assisting patients with medication use, showing compassion towards patients, and empowering patients against stigma.

Conclusion

These findings of the study can be used to develop domain-specific PROM and PREM questions for the national HIV quality care register.
Optimization design of interdigitated microelectrodes with an insulation layer on the connection tracks to enhance efficiency of assessment of the cell viability
Authors: Sherif Sameh. , Ghallab Yehya H. , AbdelRaheem Omnia , Ziko Laila , Siam Rania , Ismail Yehea
Published: May 2023

Background

Microelectrical Impedance Spectroscopy (µEIS) is a tiny device that utilizes fluid as a working medium in combination with biological cells to extract various electrical parameters. Dielectric parameters of biological cells are essential parameters that can be extracted using µEIS. µEIS has many advantages, such as portability, disposable sensors, and high-precision results.

Results

The paper compares different configurations of interdigitated microelectrodes with and without a passivation layer on the cell contact tracks. The influence of the number of electrodes on the enhancement of the extracted impedance for different types of cells was provided and discussed. Different types of cells are experimentally tested, such as viable and non-viable MCF7, along with different buffer solutions. This study confirms the importance of µEIS for in vivo and in vitro applications. An essential application of µEIS is to differentiate between the cells’ sizes based on the measured capacitance, which is indirectly related to the cells’ size. The extracted statistical values reveal the capability and sensitivity of the system to distinguish between two clusters of cells based on viability and size.

Conclusion

A completely portable and easy-to-use system, including different sensor configurations, was designed, fabricated, and experimentally tested. The system was used to extract the dielectric parameters of the Microbeads and MCF7 cells immersed in different buffer solutions. The high sensitivity of the readout circuit, which enables it to extract the difference between the viable and non-viable cells, was provided and discussed. The proposed system can extract and differentiate between different types of cells based on cells’ sizes; two other polystyrene microbeads with different sizes are tested. Contamination that may happen was avoided using a Microfluidic chamber. The study shows a good match between the experiment and simulation results. The study also shows the optimum number of interdigitated electrodes that can be used to extract the variation in the dielectric parameters of the cells without leakage current or parasitic capacitance.
Prenatal detection of Kaposiform Hemangioendothelioma with Kasabach–Merritt phenomenon: a case report
Authors: Maurya Vinay , Sharma Shweta , Singh Samarjeet , Sharma Pankaj , Gupta Amul
Published: May 2023

Background

Kaposiform Hemangioendothelioma is a rare vascular neoplasm that typically presents in neonates and infancy. Most of the cases of Kaposiform Hemangioendothelioma are reported in neonates (60%) and infancy (93%), and very few cases have been reported prenatally. We describe here a case which was diagnosed prenatally in the 3rd trimester with rapid growth of upper limb and appearance of non-immune hydrops.

Case presentation

A 25-year-old primigravida, an antenatally booked case, presented for routine third trimester level III scan at 34-week gestation. Level I scan for nasal bone and nuchal translucency at 12 weeks and level II anomaly scan at 20 weeks were normal. Level III ultrasound scan revealed increased echogenicity and hypertrophy of soft tissues of right upper limb and trunk involving both the subcutaneous and muscular compartments. Fetal middle cerebral artery Doppler, echocardiography and magnetic resonance imaging revealed fetal anemia, cardiac failure, and non-immune hydrops. These findings with hemodynamic changes and rapid evolution were suggestive of Kaposiform Hemangioendothelioma with Kasabach–Merritt phenomenon.

Conclusion

The diagnosis of Kaposiform Hemangioendothelioma should be suspected in prenatal period if there is unilateral hypertrophy of limb which has evolved rapidly over a short interval of time and shows findings suggestive of Kasabach–Merritt Phenomenon. Prenatal presentation is life threatening if it is associated with poor fetal hemodynamics. Prenatal counseling in such cases should include advice on termination of pregnancy with emphasis on neonatal management.
Correlation between the perineural invasion and neck metastasis in patients with laryngeal carcinoma: a cross sectional study
Authors: Hamela Mo’men Ali , Bestawy Ahmed , Gharib Fadi
Published: May 2023

Background

One of the most problematic issues of laryngeal carcinoma is recurrence after surgery one of the causes of recurrence this study tries to find its relevance is the peri neural invasion.

Aim of the work

To determine whether there is a relationship between perineural invasion and cervical nodal metastases of laryngeal squamous cell carcinoma.

Methods

Between December 2019 and September 2020, this study was conducted on 30 individuals who had laryngeal SCC. After the surgical removal of the tumor, a histological examination was done to check for the existence of perineural invasion, which was later linked to the cervical nodal metastases.

Results

Of our patients 26.7% (8/30) had perineural invasion. Perineural invasion and cervical nodal metastasis were statistically significantly associated (P value = 0.018).

Conclusion

A strong histologic predictor of cervical nodal metastases is perineural invasion.
Rationale and clinical application of antimicrobial stewardship principles in the intensive care unit: a multidisciplinary statement
Authors: Cortegiani Andrea , Antonelli Massimo , Falcone Marco , Giarratano Antonino , Girardis Massimo , Leone Marc , Pea Federico , Stefani Stefania , Viaggi Bruno , Viale Pierluigi
Published: May 2023

Background

Antimicrobial resistance represents a major critical issue for the management of the critically ill patients hospitalized in the intensive care unit (ICU), since infections by multidrug-resistant bacteria are characterized by high morbidity and mortality, high rates of treatment failure, and increased healthcare costs worldwide. It is also well known that antimicrobial resistance can emerge as a result of inadequate antimicrobial therapy, in terms of drug selection and/or treatment duration. The application of antimicrobial stewardship principles in ICUs improves the quality of antimicrobial therapy management. However, it needs specific considerations related to the critical setting.

Methods

The aim of this consensus document gathering a multidisciplinary panel of experts was to discuss principles of antimicrobial stewardship in ICU and to produce statements that facilitate their clinical application and optimize their effectiveness. The methodology used was a modified nominal group discussion.

Conclusion

The final set of statements underlined the importance of the specific interpretation of antimicrobial stewardship’s principles in critically ill patient management, quasi-targeted therapy, the use of rapid diagnostic methods, the personalization of antimicrobial therapies’ duration, obtaining microbiological surveillance data, the use of PK/PD targets, and the use of specific indicators in antimicrobial stewardship programs.
President's Page: Fostering collaboration for regional success: Uniting local and global perspectives
Authors: Chandola Sandeep K.
Published: May 2023

When Ken Tubman approached me about writing the President's Page for TLE, I felt both honored and thrilled to be given the opportunity. However, it took me a while to decide on a topic that would truly resonate with myself and my fellow professionals. After much contemplation, I chose to write about something close to my heart — how SEG members in the Asia-Pacific region, particularly Southeast Asia, have been working to balance regional needs with the evolving global perspective of the Society.
Reviews
Authors: Aitken Julie
Published: May 2023

Modern Computer Vision with PyTorch: Explore Deep Learning Concepts and Implement Over 50 Real-World Image Applications, by V. Kishore Ayyadevara and Yeshwanth Reddy, 2020.
Endocrine Therapy for Primary and Secondary Prevention After Diagnosis of High-Risk Breast Lesions or Preinvasive Breast Cancer
Authors: Laws Alison , Punglia Rinaa S.
Published: May 2023

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice.

Patients with high-risk breast lesions (HRLs) or preinvasive breast cancers face an elevated risk of future breast cancer diagnoses. Endocrine therapy in this setting reduces the risk of a future diagnosis but does not confer improved survival, thus the side effects of primary/secondary prevention must be considered relative to the benefits. Here, we discuss the available chemoprevention regimens for patients with HRLs and considerations for selecting a regimen, as well as the decision making surrounding use of adjuvant endocrine therapy for patients with ductal carcinoma in situ (DCIS). For patients with HRLs, available chemoprevention regimens differ by menopausal status, including tamoxifen 20 mg once daily for 5 years and more recently tamoxifen 5 mg once daily for 3 years in both premenopausal and postmenopausal women as well as raloxifene or aromatase inhibitors for postmenopausal women. We recommend a shared decision-making approach with attention to patient preferences related to risk tolerance and side-effect profiles. Low-dose tamoxifen appears to be a particularly favorable choice that is well tolerated, without risk of serious adverse events and offers comparable risk reduction to other regimens. For DCIS, the benefit of endocrine therapy in addition to radiation is small, and appears to be driven mainly by a reduction in contralateral breast diagnoses or new breast cancers. A strategy that reduces the side-effect profile of chemoprevention such as low-dose tamoxifen may be especially appealing in the setting of secondary prevention.
Closing the Testing Gap: Standardization of Comprehensive Biomarker Testing for Metastatic Non–Small-Cell Lung Cancer in a Large Community Oncology Practice
Authors: Waterhouse David M. , Ward Patrick , Arnal Suzzette , Neubauer Marcus , Drosick David R. , Davies Dan , Mendenhall Molly A.
Published: May 2023

PURPOSE:

Non–small-cell lung cancer (NSCLC), the leading cause of cancer death in the United States, accounts for 85% of all lung cancer cases. Biomarker testing is an integral part of the care of patients with NSCLC. Despite broad consensus recommendations that all patients with metastatic NSCLC (mNSCLC) undergo comprehensive biomarker testing (comprehensive genomic profiling and PD-L1), testing rates remain suboptimal.

METHODS:

The primary goal of this project was to apply National Comprehensive Cancer Network (NCCN) guidelines for comprehensive biomarker testing to all new patients with mNSCLC within a large community practice. Plan-Do-Study-Act methodology was used, with cycle 1 focused on provider education and the creation of a mNSCLC initial consult Note (electronic health record template/McKesson iKnowMed G2) and accompanying order set. Staging, template/order set utilization, and comprehensive biomarker testing rates were recorded while workflow processes were monitored. Cycle 2 centered on improved cancer staging, data analytic reporting, auditing, and reeducation.

RESULTS:

The comprehensive biomarker testing rates increased from a historic rate of 68% to 92.7% during the 1-year intervention period. The template utilization rate was 71% with complete staging (TNM stage and relevant biomarkers) documented in 40%.

CONCLUSION:

Implementation and standardization of comprehensive biomarker testing of patients with mNSCLC in a large multisite community-based oncology practice is feasible and results in significant improvement in comprehensive biomarker testing and reporting. Establishing reliable and measurable tracking metrics to ensure that these new processes are used and maintained can assist in scaling these processes. Efforts to scale this best practice are planned across the US Oncology Network.
Containing the Canon
Authors: Gilmore Shawn
Published: May 2023

Ever since Star Wars became a franchise -- immediately after the release of A New Hope - -there have been a wide variety of efforts to structure, explain, and systematize its ever-expanding narrative universe. Going under various names, including the "Extended Universe," the Star Wars franchise beyond the core films has always been somewhat contentious, both as markers of fan knowledge and as potential for nearly endless corporate profit. What was originally kept in a vast archive of narrative data at Lucasfilm led to a hierarchy of canons and canonicity, which was distributed back to fans via elaborate reference books and contained within Star Wars plots as holocrons kept as lore in Jedi and Sith temples. This paper examines the fate of that canonicity in the wake of the 2012 purchase of Lucasfilm by Disney, exploring how various aspects of these already commodified franchise elements have been contained and redeployed as Disney both continued the Skywalker saga of films and elaborated the Star Wars franchise in new ways.