bluuebunny/crossref_metadata_2025 huggingface dataset:
ALL-RIC trial protocol: a comparison of reduced dose total body irradiation (TBI) and cyclophosphamide with fludarabine and melphalan reduced intensity conditioning in adults with acute lymphoblastic leukaemia (ALL) in complete remission
Authors: Marks David I , Castleton Anna , Olavarria Eduardo , Gilleece Maria , Fielding Adele , Mikhaeel George , Beasley Matthew , Diez Patricia , Jackson Aimee , Hodgkinson Andrea , Elhanied Mohamed , Chakraverty Ronjon
Published: June 2023

Introduction

The usage of a T-cell depleted, reduced intensity conditioning (RIC) approach to haematopoietic cell transplantation (HCT) in adult patients with acute lymphoblastic leukaemia (ALL) over 40 years of age and in first complete remission (CR) has resulted in encouraging rates of event-free and overall survival in a population of adults with high risk disease. However, relapse rates remain high—with disease progression being the major cause of treatment failure. Using different, more powerful conditioning approaches is the logical next step in examining the role of RIC allogeneic HCT in adult ALL.

Methods and analysis

The ALL-RIC trial is a two-arm, phase II, multicentre, randomised clinical trial in adult patients with ALL in first or second CR, who are undergoing allogeneic HCT. Comparison of a novel RIC transplant conditioning regimen using reduced-dose total body irradiation (TBI), cyclophosphamide and alemtuzumab, is made against a standardised RIC approach using fludarabine, melphalan and alemtuzumab. The primary outcome of the study is disease-free survival at 3 years, defined as time from randomisation to the first of either relapse or death from any cause. Patients who are still alive and progression-free at the end of the trial will be censored at their last date known to be alive. Secondary outcomes include overall survival and non-relapse mortality.

Ethics and dissemination

The protocol was approved by the East Midlands—Leicester Central Research Ethics committee (18/EM/0112). Initial approval was received on 12 June 2018. Current protocol version (V.6.0) approval obtained on 18 November 2019. The Medicines and Healthcare products Regulatory Agency (MHRA) also approved all protocol versions. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.

Trial registration number

EudraCT Number: 2017-004800-23.

ISRCTN99927695.
Age-specific and genotype-specific carcinogenic human papillomavirus prevalence in a country with a high cervical cancer burden: results of a cross-sectional study in Estonia
Authors: Pärna Kersti , Nygård Mari , Tisler Anna , Toompere Karolin , Naaber Paul , Ratnik Kaspar , Ķīvīte Urtāne Anda , Zodzika Jana , Stankūnas Mindaugas , Baltzer Nicholas , Uusküla Anneli
Published: June 2023

Objectives

To describe age-specific and type-specific carcinogenic human papillomavirus (HPV) prevalence prior to large-scale effect of HPV vaccines in Estonia and to analyse the risk factors associated with carcinogenic HPV.

Design

Cross-sectional study using self-administered questionnaire and self-collected vaginal swabs for detection of HPV infection.

Setting

Estonian Biobank database.

Participants

Stratified random sample of women aged 30–33, 57–60 and 67–70 years living in one of the three largest counties in Estonia. Of 3065 women approached, 1347 (43.9%) returned questionnaires and specimens for HPV DNA detection.

Outcome measures

HPV prevalence and fully adjusted ORs with 95% CIs for risk factors.

Results

HPV prevalence was highest among women aged 30–33 years (18.7%; 95% CI 15.8 to 21.9) followed by those aged 67–70 years (16.7%; 95% CI 12.4 to 22.0) and 57–60 years (10.2%; 95% CI 7.8 to 13.3). HPV16 and HPV56 were the most common among women aged 30–33 years (both 4.0%; 95% CI 2.7 to 5.9), and HPV68 was the most common among women aged 57–60 years (2.8%; 95% CI 1.5 to 4.7) and 67–70 years (6.4%; 95% CI 3.6 to 10.4). Vaccination with nonavalent vaccine would have halved the carcinogenic HPV prevalence among women aged 30–33 years. The odds of infection with carcinogenic HPV were higher among women with six or more sexual partners among younger (OR 2.99; 95% CI 1.54 to 5.81) and older (OR 3.80; 95% CI 1.25 to 11.55) women and lower (OR 0.35; 95% CI 0.17 to 0.72) among younger married women.

Conclusions

This study demonstrated U-shaped age-specific genotype profile of carcinogenic HPV prevalence, indicating that public health providers should focus on developing exit strategies for the cervical cancer screening programme in Estonia with a possible extension of HPV testing beyond the current screening age of 65 years. Generalisability of the findings of this study may be affected by the low response rate.
Shared characteristics of intervention techniques for oral vocabulary and speech comprehensibility in preschool children with co-occurring features of developmental language disorder and a phonological speech sound disorder: protocol for a systematic review with narrative synthesis
Authors: Rodgers Lucy , Botting Nicola , Cartwright Martin , Harding Sam , Herman Rosalind
Published: June 2023

Introduction

Evidence suggests that over one-third of young children with developmental language disorder (DLD) or speech sound disorder (SSD) have co-occurring features of both. A co-occurring DLD and SSD profile is associated with negative long-term outcomes relating to communication, literacy and emotional well-being. However, the best treatment approach for young children with this profile is not understood. The aim of the proposed review is to identify intervention techniques for both DLD and SSD, along with their shared characteristics. The findings will then be analysed in the context of relevant theory. This will inform the content for a new or adapted intervention for these children.

Methods and analysis

This search will build on a previous systematic review by Roulstoneet al(2015) but with a specific focus on oral vocabulary (DLD outcome) and speech comprehensibility (SSD outcome). These outcomes were identified by parents and speech and language therapists within the prestudy stakeholder engagement work. The following databases will be searched for articles from January 2012 onwards: Ovid Emcare, MEDLINE Complete, CINAHL, APA PsycINFO, Communication Source and ERIC. Two reviewers will independently perform the title/abstract screening and the full-text screening with the exclusion criteria document being revised in an iterative process. Articles written in languages other than English will be excluded. Data will be extracted regarding key participant and intervention criteria, including technique dosage and delivery details. This information will then be pooled into a structured narrative synthesis.

Ethics and dissemination

Ethical approval is not needed for a systematic review protocol. Dissemination of findings will be through peer-reviewed publications, social media, and project steering group networks.

PROSPERO registration number

CRD4202237393.
Paving the way for solutions improving access to kidney transplantation: a qualitative study from a multistakeholder perspective
Authors: Merweland Ruben van , Busschbach Jan J V , van de Wetering Jacqueline , Ismail Sohal
Published: June 2023

Objectives

The aim of this study was to obtain an in-depth perspective from stakeholders involved in access to kidney transplantation to pave the way for solutions in improving access to kidney transplantation. This study qualitatively explored factors influencing optimal access to kidney transplantation from a broad stakeholder perspective.

Design

A qualitative study was performed using semistructured interviews both in focus groups and with individual participants. All interviews were recorded, transcribed and coded according to the principles of grounded theory.

Setting

Participants were healthcare providers (geographically spread), patients and (former living) kidney donors, policy-makers and insurers.

Participants

Stakeholders (N=87) were interviewed regarding their perceptions, opinions and attitudes regarding access to kidney transplantation.

Results

The problems identified by stakeholders within the domains—policy, medical, psychological, social and economic—were acknowledged by all respondents. According to respondents, more efforts should be made to make healthcare providers and patients aware of the clinical guideline for kidney transplantation. The same opinion applied to differences in medical inclusion criteria used in the different transplantation centres. Stakeholders saw room for improvement based on psychological and social themes, especially regarding the provision of information. Many stakeholders described the need to rethink the current economic model to improve access to kidney transplantation. This discussion led to a definition of the most urgent problems for which, according to the respondents, a solution must be sought to optimise access to kidney transplantation.

Conclusions

Stakeholders indicated a high sense of urgency to solve barriers in patient access to kidney transplantation. Moreover, it appears that some barriers are quite straightforward to overcome; according to stakeholders, it is striking that this process has not yet been overcome. Stakeholders involved in kidney transplantation have provided directions for future solutions, and now it is possible to search for solutions with them.
Pragmatic multicentre stepped-wedge cluster randomised trial to investigate the effectiveness of community-based falls prevention programme for older adults with falls risk in Singapore: a protocol paper
Authors: Tan Pey June , Ginting Mimaika Luluina , Lim Zoe Zon Be , Balachandar Nivedha , Sultana Rehena , Kadir Mumtaz Mohamed , Xu Tianma , Ismail Noor Hafizah , Yap Joyce Kwee Yong , Wong Sweet Fun , Yoong Joanne , Matchar David Bruce , Hill Keith , Wong Chek Hooi
Published: June 2023

Introduction

Falls are an important public health issue with consequences that include injuries, quality of life reduction and high healthcare costs. Studies show that falls prevention strategies are effective in reducing falls rate among community-dwelling older adults. However, the evaluation for effectiveness was usually done in a controlled setting with homogeneous population, and thus may not be generalisable to a wider population. This study aims to evaluate the impact of community falls prevention programmes with group-based strength and balance exercises, on falls risk and health outcomes for older adults with falls risk in Singapore.

Methods and analysis

This is a pragmatic closed cohort stepped-wedge cluster randomised trial design study, which involves sequential crossover of clusters from the waitlist control condition to the intervention condition, with the sequence of crossover randomly determined. The intervention will be sequentially rolled out to 12 clusters (a minimum of 5 participants/cluster), over 6 time periods with 8-week intervals in Central and North regions of Singapore. The primary analysis will be conducted under the intention-to-treat principle. A general linear mixed model or generalised estimating equation analysis appropriate for a multilevel longitudinal study incorporating an appropriate error distribution and link function will be used. Markov model will be developed to estimate the incremental cost per quality-adjusted life years and incremental cost per fall prevented from the implementation of falls prevention strategies from a societal perspective. Conditional on there being clinically relevant differences in short-term outcomes, we will implement simulation modelling to project the long-term divergence in trajectories for outcomes and costs using the Markov model.

Ethics and dissemination

Ethics approval has been obtained. Results will be disseminated in publications and other relevant platforms.

Trial registration number

NCT04788251.
Study protocol: pneumonia and inhaled corticosteroid treatment patterns in chronic obstructive pulmonary disease – a cohort study using sequence analysis (PICCS)
Authors: Klitgaard Allan , Ibsen Rikke , Hilberg Ole , Løkke Anders
Published: June 2023

Introduction

Treatment with inhaled corticosteroids (ICS) is a widely used treatment in chronic obstructive pulmonary disease. The main effects include a reduction in the number of exacerbations and, for some patients, an increase in expected mortality. Unfortunately, the treatment is also linked to an increased risk of pneumonia, and very little is known about which patients experience this increased risk. There is a need for identification of patient characteristics associated with increased risk of pneumonia and treatment with ICS.

Methods and analysis

This is a register-based cohort study that uses the nationwide Danish registers. Data from several registers in the years 2008–2018 will be merged on an individual level using the personal identification numbers that are unique to every citizen in Denmark. Clusters based on pneumonia incidence and ICS treatment patterns will be explored with a sequence analysis in a 3-year follow-up period.

Ethics and dissemination

This is a register-based study and research ethics approval is not required according to Danish Law and National Ethics Committee Guidelines. The results will be submitted to peer-reviewed journals and reported at appropriate national and international meetings.
Adaptive nanopore sequencing to determine pathogenicity ofBRCA1exonic duplication
Authors: Filser Mathilde , Schwartz Mathias , Merchadou Kevin , Hamza Abderaouf , Villy Marie-Charlotte , Decees Antoine , Frouin Eléonore , Girard Elodie , Caputo Sandrine M , Renault Victor , Becette Véronique , Golmard Lisa , Servant Nicolas , Stoppa-Lyonnet Dominique , Delattre Olivier , Colas Chrystelle , Masliah-Planchon Julien
Published: June 2023

BRCA1andBRCA2are tumour suppressor genes that have been characterised as predisposition genes for the development of hereditary breast and ovarian cancers among other malignancies. The molecular diagnosis of this predisposition syndrome is based on the detection of inactivating variants of any type in those genes. But in the case of structural variants, functional consequences can be difficult to assess using standard molecular methods, as the precise resolution of their sequence is often impossible with short-read next generation sequencing techniques. It has been recently demonstrated that Oxford Nanopore long-read sequencing technology can accurately and rapidly provide genetic diagnoses of Mendelian diseases, including those linked to pathogenic structural variants. Here, we report the accurate resolution of a germline duplication event of exons 18–20 ofBRCA1using Nanopore sequencing with adaptive sampling target enrichment. This allowed us to classify this variant as pathogenic within a short timeframe of 10 days. This study provides a proof-of-concept that nanopore adaptive sampling is a highly efficient technique for the investigation of structural variants of tumour suppressor genes in a clinical context.
Outcomes in patients with large vessel occlusion strokes undergoing mechanical thrombectomy with concurrent COVID-19: a nationwide retrospective analysis
Authors: Ramsay Ian A , Fountain Hayes , Elarjani Turki , Govindarajan Vaidya , Silva Michael , Abdelsalam Ahmed , Burks Joshua D , Starke Robert M , Luther Evan
Published: June 2023

Background

Preliminary studies show that patients with large vessel occlusion (LVO) acute ischemic strokes have worse outcomes with concurrent COVID-19 infection. We investigated the outcomes for patients with LVO strokes undergoing mechanical thrombectomy (MT) with concurrent COVID-19 infection.

Methods

The National Inpatient Database (NIS) was used for our analysis. Patients in the year 2020 with an ICD-10 diagnosis code for acute ischemic stroke and procedural code for MT were included with and without COVID-19. Odds ratios (OR) were calculated using a logistic regression model with age, sex, stroke location, Elixhauser comorbidity score, and other patient variables deemed clinically relevant as covariates.

Results

Patients in the COVID-19 group were younger (64.3±14.4 vs 69.4±14.5 years, P<0.001), had a higher rate of inpatient mortality (22.4% vs 10.1%, P<0.001), and a longer length of stay (10 vs 6 days, P<0.001). Patients with COVID-19 had higher odds of death (OR 2.78, 95% CI 2.11 to 3.65) and lower odds of a routine discharge (OR 0.65, 95% CI 0.48 to 0.89). There was no difference in the odds of subsequent stroke and cerebral hemorrhage, but patients with COVID-19 had statistically significantly higher odds of respiratory failure, pulmonary embolism, deep vein thrombosis, myocardial infarction, acute kidney injury, and sepsis.

Conclusions

Patients with LVOs undergoing MT within the 2020 NIS database had worse outcomes when co-diagnosed with COVID-19, likely due to non-neurological manifestations of COVID-19.
Policy-relevant differences between secondhand and thirdhand smoke: strengthening protections from involuntary exposure to tobacco smoke pollutants
Authors: Matt Georg E , Greiner Lydia , Record Rachael A , Wipfli Heather , Long Jamie , Dodder Nathan G , Hoh Eunha , Lopez Galvez Nicolas , Novotny Thomas E , Quintana Penelope J E , Destaillats Hugo , Tang Xiaochen , Snijders Antoine M , Mao Jian-Hua , Hang Bo , Schick Suzaynn , Jacob Peyton , Talbot Prue , Mahabee-Gittens E Melinda , Merianos Ashley L , Northrup Thomas F , Gundel Lara , Benowitz Neal L
Published: June 2023

Starting in the 1970s, individuals, businesses and the public have increasingly benefited from policies prohibiting smoking indoors, saving thousands of lives and billions of dollars in healthcare expenditures. Smokefree policies to protect against secondhand smoke exposure, however, do not fully protect the public from the persistent and toxic chemical residues from tobacco smoke (also known as thirdhand smoke) that linger in indoor environments for years after smoking stops. Nor do these policies address the economic costs that individuals, businesses and the public bear in their attempts to remediate this toxic residue. We discuss policy-relevant differences between secondhand smoke and thirdhand smoke exposure: persistent pollutant reservoirs, pollutant transport, routes of exposure, the time gap between initial cause and effect, and remediation and disposal. We examine four policy considerations to better protect the public from involuntary exposure to tobacco smoke pollutants from all sources. We call for (a) redefining smokefree as free of tobacco smoke pollutants from secondhand
and
thirdhand smoke; (b) eliminating exemptions to comprehensive smoking bans; (c) identifying indoor environments with significant thirdhand smoke reservoirs; and (d) remediating thirdhand smoke. We use the case of California as an example of how secondhand smoke-protective laws may be strengthened to encompass thirdhand smoke protections. The health risks and economic costs of thirdhand smoke require that smokefree policies, environmental protections, real estate and rental disclosure policies, tenant protections, and consumer protection laws be strengthened to ensure that the public is fully protected from and informed about the risks of thirdhand smoke exposure.
Multiple forms of bioimmuration in a coral–crinoid–bryozoan association from the Middle Devonian Onondaga Formation of southeastern Ontario
Authors: Thomka James R. , Gunderson Lilian K.
Published: June 2023

A large favositid tabulate coral colony from the Middle Devonian Edgecliff Member of the Onondaga Formation, collected from Port Colborne, southernmost Ontario, is described herein because of several noteworthy paleontological features preserved via overgrowth by the coral. The initial substratum colonized and subsequently overgrown by the favositid was a large solitary rugose coral, and outward growth resulted in overgrowth of multiple macrofossils, including relatively long portions of large-diameter (probably camerate) crinoid columns. The crinoid columns, which likely represent portions of robust, recumbent dististelar attachment structures, are otherwise known almost entirely from isolated columnals at the collection locality and similar high-energy biostromal lithofacies in the Edgecliff Member elsewhere. One of the crinoid columns is encrusted by a stenolaemate bryozoan containing several examples of a parasitic bioclaustration structure similar to Catellocaula. Hence, the composite coral–crinoid–bryozoan association contains two forms of bioimmuration: preservation of the relatively intact crinoid columns via overgrowth and eventual incorporation into the base of the tabulate coral and preservation of the outline of the bioclaustrated organism (potentially an ascidian tunicate) via embedment in the bryozoan. This specimen serves as a testament to the diversity of biotic interactions and preservational mechanisms that occurred in Paleozoic carbonate build-ups.
Exploring departures from Schwarzschild black hole in f(R) gravity
Authors: De Falco Vittorio , Bajardi Francesco , D’Agostino Rocco , Benetti Micol , Capozziello Salvatore
Published: June 2023

Different astrophysical methods can be combined to detect possible deviations from General Relativity. In this work, we consider a class of f(R) gravity models selected by the existence of Noether symmetries. In this framework, it is possible to determine a set of static and spherically symmetric black hole solutions, encompassing small departures from the Schwarzschild geometry. In particular, when gravity is the only dominating interaction, we exploit the ray-tracing technique to reconstruct the image of a black hole, the epicyclic frequencies, and the black hole shadow profile. Moreover, when matter dynamics is also affected by an electromagnetic radiation force, we take into account the general relativistic Poynting–Robertson effect. In light of the obtained results, the proposed strategy results to be robust and efficient: on the one hand, it allows to investigate gravity from strong to weak field regimes; on the other hand, it is capable of detecting small departures from General Relativity, depending on the current observational sensitivity.
Accommodation Recommendation on Shared Platforms Considering Bidirectional Selection and Review Mechanisms
Authors: Lin Yuanyuan , Huang Chao , Zhang Xi , Li Xin , Yao Wei
Published: June 2023

In recent years, shared accommodation platforms have developed rapidly and become increasingly popular. They commonly adopt unique bidirectional selection and review mechanisms. However, most existing accommodation recommendation strategies overlook the impact of these mechanisms on the recommendation performance. To address this gap, we propose a two-stage recommendation method as Shared Accommodation Recommendation based on Bidirectional Selection and Review mechanisms (SARBSR) to improve the recommendation performance of shared accommodation. The first stage combines a multi-attribute recommendation method (MAR) with a hybrid recommendation method based on similarity and ratings (HRSR) to predict guests’ preferences and generate candidate lists. In the second stage, considering bidirectional selection and reviews mechanisms, we assess hosts’ willingness to accept guests’ requests via trust evaluation and select rooms from the candidate lists as the final recommendation strategy. To evaluate the performance of SARBSR, an empirical study on real-world data from Airbnb is conducted. The results demonstrate the validity of SARBSR and indicate the necessity of considering bidirectional selection and review mechanisms.
Revolutionizing Diabetes Disease Prediction Through Novel Machine Learning Techniques
Authors: Singh Yogendra , Tiwari Mahendra
Published: June 2023

Diabetes is a chronic disease that affects millions of people worldwide. Accurate and timely diagnosis of diabetes is crucial for its effective treatment and management. While machine learning has shown promise in predicting the disease, missing data, outliers, class imbalance and limitations of classifiers can hinder accuracy.

To address these challenges, we propose a novel machine learning approach that combines adaptive iterative imputation (AII) for missing value imputation, dynamic ensemble isolation forest (DE-IF) for outlier detection and removal, Iterated KMeans SMOTEENN (IKMSENN) for class imbalance, and an adaptive extra tree classifier (AETC) for classification. Our approach is evaluated using the Pima Indian Diabetes Dataset (PIDD), a widely used benchmark dataset in diabetes disease prediction.

Experimental results show that our approach outperforms several state-of-the-art machine learning models in terms of accuracy, precision, recall, [Formula: see text]-measure, and the area under the receiver operating characteristic (ROC) curve (AUC-ROC). Our approach achieved an accuracy of 98.58%, with a precision of 0.986, recall of 0.987, [Formula: see text]-measure of 0.985, and ROC of 0.965 on the PIDD dataset.

Our research presents a significant contribution to the field of diabetes disease prediction by introducing novel machine learning approaches that address common challenges such as missing data, outliers and class imbalance, as well as limitations of classifiers. Our approach has the potential to greatly improve the accuracy and effectiveness of diabetes disease prediction and has important implications for the diagnosis and management of the disease.
Tips for Supporting Students with Social Skill, Mental Health, and Communication Disabilities in Digital Settings
Authors: Park Tulare Williams , Sheward Kari L. , Rogers-Shaw Carol
Published: June 2023

Teaching online learners with social skill, mental health, and communication disabilities requires post-secondary instructors to become more than content experts. The purpose of this article is to provide recommendations for postsecondary instructors for building inclusive communities, focusing on accessible course design, and increasing specialized professional knowledge that serves all learners, saves planning time, and diminishes frustration from excessive individualization of instruction.
Remarking the Unmarked: An Anthropology of Masculinity Redux
Authors: Gutmann Matthew
Published: June 2023

This review surveys studies of men and masculinities in anthropology and ethnography from other disciplines, as well as theoretical frameworks and debates among anthropologists and other relevant scholars in the field. It also aims to assess developments in these studies since an earlier Annual Review of Anthropology article was published on this subject. By considering the ethnographic boom in men and masculinities studies across the globe since 2000, increasingly authored by anthropologists from the Global South, this review considers anthropology's singular contributions topically and conceptually—for example, masculinity and militarism, men and public health, gender inequalities, and trans*social movements—including through innovative research in biological and linguistic anthropology and archaeology. Throughout, this article reflects on the extent to which anthropologists have moved (and if they should have moved) beyond the study of women or men to instead explore gender, sex, and sexuality of humans and nonhuman animals in less binary frameworks.
Less sodium, more potassium, or both: population-wide strategies to prevent hypertension
Authors: Nissaisorakarn Voravech , Ormseth George , Earle William , Morales-Alvarez Martha Catalina , Hiremath Swapnil , Juraschek Stephen P.
Published: June 2023

Hypertension is among the most prevalent medical conditions globally and a major contributor to chronic kidney disease, cardiovascular disease, and death. Prevention through nonpharmacological, population-level interventions is critically needed to halt this worldwide epidemic. However, there are ongoing disagreements as to where public policy efforts should focus. Recently the Salt Substitute and Stroke Study demonstrated the efficacy of substituting table salt with potassium salt to reduce the risk of stroke, major cardiovascular events, and death. However, this sparked debate over whether sodium or potassium should be prioritized in countries where table salt substitution was less feasible. In this commentary, we summarize arguments in favor of either strategy: reduced sodium or increased potassium intake. Moreover, we discuss evidence and policy approaches related to either or combined approaches relevant to cultural context. Ultimately, there is an urgent need for policies that both reduce sodium and increase potassium intake; however, identifying a strategy that fits cultural context will be key to improve population-wide blood pressures.
Phytochemical Content, Antibacterial Activity, and Antioxidant, Anti‐Inflammatory, and Cytotoxic Effects of Traditional Medicinal Plants against Respiratory Tract Bacterial Pathogens
Authors: Matotoka Mashilo M. , Mashabela Gabriel T. , Masoko Peter
Published: June 2023

Respiratory tract infections (RTIs) are frequent ailments among humans and are a high burden on public health. This study aimed to determine the in vitro antibacterial, anti‐inflammatory, and cytotoxic effects of indigenous medicinal plants used in the treatment of RTIs, namely, Senna petersiana, Gardenia volkensii, Acacia senegal, and Clerodendrum glabrum. Dried leaves were extracted using various organic solvents. Antibacterial activity was quantified using the microbroth dilution assay. Protein denaturation assays were used to evaluate anti‐inflammatory activity. The cytotoxicity of the extracts towards THP‐1 macrophages was evaluated using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Antioxidant activity was determined using free radical scavenging activity and ferric‐reducing power. Total polyphenolics were quantified. Liquid chromatography mass spectrometry was used to evaluate the acetone plant extracts. Nonpolar extracts had noteworthy antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Mycobacterium smegmatis where MIC values ranged between 0.16 and 0.63 mg/mL. At 100 μg/mL, A. senegal, G. volkensii, and S. petersiana had a nonsignificant effect on the viability of the THP‐1 macrophages. The LC‐MS analysis of the leaf extracts of S. petersiana detected Columnidin, Hercynine, L‐Lysine citrate, and Gamma‐Linolenate. A pentacyclic triterpenoid, cochalate, was detected in G. volkensii. Two flavonoids 7‐hydroxy‐2‐(4‐methoxyphenyl)‐4‐oxo‐chroman‐5‐olate and (3R)‐3‐(2,4‐dimethoxyphenyl)‐7‐hydroxy‐4‐oxo‐chroman‐5‐olate were detected in the C. glabrum extract. The findings from this study indicated that the leaves of the selected plant extracts possess antioxidant, anti‐inflammatory, and antibacterial activity. Therefore, they may serve as good candidates for further pharmaceutical investigations.
Teaching Dental Drawings for Freshman Dental Students and Its Correlation with Manual Dexterity
Authors: Elgendy Hanan , Cui Xiaoxi , Watkins Todd , McQuistan Michelle
Published: June 2023

Objective. To assess whether the implementation of teeth drawing exercises in a dental anatomy course improves first-year (D1) dental students’ understanding of tooth morphology, their dexterity, and their clinical skills compared with D1s who did not participate in the drawing exercises. Methods. In 2020, a “Teeth Drawing Module” was implemented within the D1 dental anatomy curriculum. In this course, students learn how to draw accurate outlines of teeth. The students are required to complete two types of drawing projects. Illustrations and instructions of teeth drawings that are outlined in a manual drawing book, PowerPoint presentations, illustration videos, and assessments are provided. Students’ grades in the drawing module, waxing skills assessments, and their didactic exams were used to evaluate and assess the correlation between their drawing aptitude and their manual skills. Students who took the drawing course were compared with students who did not take the drawing course to determine if the drawings improved students’ understanding of tooth morphology, their dexterity, and their clinical skills. A comprehensive survey was also developed and distributed to students who had the drawing module in their curriculum. Results. Students who participated in the drawing module were more successful in the dental anatomy course compared with students in the control classes. Classes that had drawing exercises scored significantly higher in all dental anatomy waxing exercises compared with classes that did not have drawing exercises (

p
<
0.001

). There was a significant positive correlation between drawing and waxing scores (

p
<
0.05

). Moreover, there was a significant positive correlation between drawing and didactic scores (

p
<
0.001

). Conclusions. Drawing exercises can be useful instruments for effectively representing and integrating the spatial domain of anatomical information. Teeth drawings as an adjunctive tool offer excellent visualization and allow students to improve their manual dexterity and knowledge in the dental anatomy course.
Liver Segment Disposition of Hepatocellular Carcinoma Predicts Microvascular Invasion
Authors: Forlemu Arnold Nongmoh , Nana Sede Mbakop Raissa , Bandaru Praneeth , Gayam Vijay , Moparty Hamsika , Sempokuya Tomoki , Pradhan Faruq , Reddy Madhavi , Olivera Marco
Published: June 2023

Background. Hepatocellular carcinoma (HCC) is a leading cause of cancer morbidity and mortality. Findings of microvascular invasion (MVI) in patients with HCC have emerged as an important prognostic factor for poor survival after tumor resection. Aim. This study evaluated the relation between MVI and HCC within various anatomical Couinaud’s segments of the liver. Method. A multicenter retrospective review of HCC records was conducted from 2012 to 2017. HCC cases were identified using ICD-9 and 10 codes 155, C22.0, and C22.8. HCC patients who underwent liver transplants were included in this study. Liver segment of the location of HCC was obtained from radiographic records, and MVI information was obtained from pathology reports. Segmental distributions of HCC in MVI versus non-MVI groups were compared using Wilcoxon rank sum tests.

p

value was set at <0.05. Results. We analyzed 120 HCC patients who underwent liver transplantation. The mean age of our cohort was 57 years, and the most common etiology of liver disease was hepatitis C at 58.3%. The median HCC size was 3.1 cm, and MVI was present in 23.3% of the explanted specimens. MVI was 2 to 3 times significantly higher in patients with HCC affecting segments 2 and 3 and segments 4b and 5 (

p
=
0.01

). Moreover, median survival was significantly lower in patients with MVI versus those without MVI (50 vs. 137 months,

p
<
0.05

). Conclusion. MVI was significantly higher in HCC tumors located in liver segments 2 and 3 and 4b and 5, and survival was lower in patients with MVI compared with those without.
Gonioscopy-Assisted Transluminal Trabeculotomy following Failed Glaucoma Surgery in Primary Congenital Glaucoma: One-Year Results
Authors: Elhusseiny Abdelrahman M. , Aboulhassan Reem M. , El Sayed Yasmine M. , Gawdat Ghada I. , Elhilali Hala M.
Published: June 2023

Purpose. To evaluate the one-year outcomes of gonioscopy-assisted transluminal trabeculotomy (GATT) in primary congenital glaucoma (PCG) with a history of prior glaucoma surgery. Methods. A retrospective chart review was performed to identify all PCG

patients
≤
16

years who underwent GATT surgery at Cairo University Children’s Hospital from January 2016 to March 2022. Pre- and postoperative intraocular pressure (IOP) and glaucoma medications were collected at 1, 3, 6, 9, 12, and last follow-up visits. Success was defined as

IOP
≤
21

 mmHg without (complete) or with (qualified) glaucoma medications at the last follow-up. Results. Seven eyes of 6 subjects were included in the study. The mean IOP was statistically significantly reduced from

25.7
±
5.9

 mmHg preoperatively to a mean IOP of

 
12
±
1.5

 mmHg (

P
=
0.001

) at 12 months and

11.5
±
1.2

 mmHg (

P
=
0.001

) at the last follow-up visit. Six eyes (85.7%) achieved complete success, and one eye (14.2%) achieved qualified success. No patients required further glaucoma procedures. No serious intra- or postoperative complications were identified. Conclusions. Our early experience highlights that GATT can be performed as an alternative procedure before considering conjunctival or scleral glaucoma surgeries.
Mechanism and Pharmacodynamic Substance Basis of Raw and Wine-Processed Evodia rutaecarpa on Smooth Muscle Cells of Dysmenorrhea Mice
Authors: Liu Yeqian , Li Hong , Chen Lei , Zhao Hongxia , Liu Jian , Gong Shan , Ma Danfeng , Chen Chunming , Zeng Shuiqing , Long Hongping , Ren Weiqiong
Published: June 2023

Objectives. Evodia rutaecarpa (ER) is a well-known herbal Chinese medicine traditionally used for analgesia in dysmenorrhea, headaches, abdominal pain, etc. Notably, the analgesic effect of wine-processed Evodia rutaecarpa (PER) was more potent than that of raw ER. This research aimed to investigate the mechanism and pharmacodynamic substance basis of raw ER and PER on smooth muscle cells of dysmenorrhea mice. Methods. Metabolomics methods based on UPLC-Q-TOF-MS were utilized to analyse the differential components of ER before and after wine processing. Afterwards, the uterine smooth muscle cells were isolated from the uterine tissue of dysmenorrhea and normal mice. The isolated dysmenorrhea uterine smooth muscle cells were randomly divided into four groups: model group, 7-hydroxycoumarin group (1 mmol/L), chlorogenic acid (1 mmol/L), and limonin (50 μmol/L). The normal group consisted of the isolated normal mouse uterine smooth muscle cells, which were repeated 3 times in each group. The cell contraction and the expression of P2X3 and Ca2+ in vitro were determined using immunofluorescence staining and laser confocal; ELISA was used for detection of PGE2, ET-1, and NO content after 7-hydroxycoumarin, chlorogenic acid, and limonin administered for 24 h. Results. The metabolomics results suggested that seven differential compounds were identified in the extracts of raw ER and PER, including chlorogenic acid, 7-hydroxycoumarin, hydroxy evodiamine, laudanosine, evollionines A, limonin, and 1-methyl-2-[(z)-4-nonenyl]-4 (1H)-quinolone. The in vitro results showed that 7-hydroxycoumarin, chlorogenic acid, and limonin were able to inhibit cell contraction and PGE2, ET-1, P2X3, and Ca2+ in dysmenorrhea mouse uterine smooth muscle cells and increase the content of NO. Conclusion. Our finding suggested that the compounds of the PER were different from those of the raw ER, and 7-hydroxycoumarin, chlorogenic acid, and limonin could improve dysmenorrhea in mice whose uterine smooth muscle cell contraction was closed with endocrine factors and P2X3-Ca2+ pathway.
A Single Bout of High Heels Dancing Causes an Increase in Circulating Markers of Muscle Tissue Degradation and MMP-3 in Young Healthy Women
Authors: Silva Jamila , Borges Leandro , Weimann Eleine , Belmiro Dias Beatriz , Gomes Faria Flavio , Ferreira Salgado Beatriz , de Freitas Paulo , Cristina Pithon-Curi Tania , Hatanaka Elaine
Published: June 2023

Prolonged wearing of high heels can cause chronic injury and inflammation. Herein, we investigated the presence of muscle injury, inflammation, and neutrophil function in young women after a single bout of stiletto dance class. Sixteen volunteers (23.4 ± 3.8 years; 61.7 ± 8.1 kg; 23.4 ± 2.3 kg/m2; and 27.2 ± 3.8% body fat) participated in the study. The plasma biomarkers matrix metalloproteinase 3 (MMP-3), muscle damage (myoglobin (Mb), total creatine kinase (CK), and lactate dehydrogenase (LDH)), and inflammation (interleukin 8 (IL-8), tumour necrosis factor-alpha (TNF-α), interleukin (IL]-1β, and IL-6) were quantified before and immediately after a single stiletto class (60 min) of moderate intensity. After class, our data showed that the plasma concentration of MMP-3, Mb, and CK increased by 56% (

p
=
0.04

; d = 0.8), 113% (

p
=
0.007

; d = 1.1), and 21% (

p
<
0.001

; d = 0.4), respectively. Reactive oxygen species produced by neutrophils and the plasma concentration of IL-8, TNF-α, IL-1β, and IL-6 were not affected under the study conditions. We concluded that a single bout of stiletto dance class caused muscle damage but did not alter the plasma concentration of proinflammatory cytokines. These findings are crucial in preventing the progress of chronic injuries that are often noted in dancers with synovitis and arthritis.
Figure 3 from Somatic Mosaic Chromosomal Alterations and Death of Cardiovascular Disease Causes among Cancer Survivors
Authors: Sun Maxine , Cyr Marie-Christyne , Sandoval Johanna , Lemieux Perreault Louis-Philippe , Busque Lambert , Tardif Jean-Claude , Dubé Marie-Pierre
Published: June 2023

Multivariable Cox regression models evaluating the effect of mCAs on incident cardiovascular phenotypes. All models are adjusted for age at baseline, sex, smoking status, chemotherapy, radiotherapy, number of days between the date of recruitment and the date of cancer diagnosis, and principal components 1 to 10. MI: myocardial infarction, NSTEMI, non-ST-elevation myocardial infarction; STEMI, ST-elevation myocardial infarction; TIA, transient ischemic attack.
Figure 2 from Somatic Mosaic Chromosomal Alterations and Death of Cardiovascular Disease Causes among Cancer Survivors
Authors: Sun Maxine , Cyr Marie-Christyne , Sandoval Johanna , Lemieux Perreault Louis-Philippe , Busque Lambert , Tardif Jean-Claude , Dubé Marie-Pierre
Published: June 2023

Multivariable Cox regression models evaluating the effect of mCAs on death of CVD causes, of CAD causes, from cancer, and death of any cause. All models are adjusted for age at baseline, sex, smoking status, chemotherapy, radiotherapy, number of days between the date of recruitment and the date of cancer diagnosis, and principal components 1 to 10. Ref., referent category (1.0).
Figure 3 from Exploring the Complex Relationship between Gut Microbiota and Risk of Colorectal Neoplasia Using Bidirectional Mendelian Randomization Analysis
Authors: Li Wanxin , Zhou Xuan , Yuan Shuai , Wang Lijuan , Yu Lili , Sun Jing , Chen Jie , Xiao Qian , Wan Zhongxiao , Zheng Ju-Sheng , Zhang Cai-Xia , Larsson Susanna C. , Farrington Susan M. , Law Philip , Houlston Richard S. , Tomlinson Ian , Ding Ke-Feng , Dunlop Malcolm G. , Theodoratou Evropi , Li Xue
Published: June 2023

Effects of genetic liability to adenoma on Enterobacteriaceae from MiBioGen consortium. A and C, Forest plot for summarizing the results of all MR methods and heterogeneity tests of IVW and MR-PRESSO. B, Scatter plot for comparison of MR methods. Abbreviations: Q-test, Cochran's Q statistic heterogeneity test. MR-PRESSO, MR pleiotropy residual sum and outlier test.
Data from Exploring the Complex Relationship between Gut Microbiota and Risk of Colorectal Neoplasia Using Bidirectional Mendelian Randomization Analysis
Authors: Li Wanxin , Zhou Xuan , Yuan Shuai , Wang Lijuan , Yu Lili , Sun Jing , Chen Jie , Xiao Qian , Wan Zhongxiao , Zheng Ju-Sheng , Zhang Cai-Xia , Larsson Susanna C. , Farrington Susan M. , Law Philip , Houlston Richard S. , Tomlinson Ian , Ding Ke-Feng , Dunlop Malcolm G. , Theodoratou Evropi , Li Xue
Published: June 2023

AbstractBackground:
Human gut microbiome has complex relationships with the host, contributing to metabolism, immunity, and carcinogenesis.
Methods:
Summary-level data for gut microbiota and metabolites were obtained from MiBioGen, FINRISK and human metabolome consortia. Summary-level data for colorectal cancer were derived from a genome-wide association study meta-analysis. In forward Mendelian randomization (MR), we employed genetic instrumental variables (IV) for 24 gut microbiota taxa and six bacterial metabolites to examine their causal relationship with colorectal cancer. We also used a lenient threshold for nine apriori gut microbiota taxa as secondary analyses. In reverse MR, we explored association between genetic liability to colorectal neoplasia and abundance of microbiota studied above using 95, 19, and 7 IVs for colorectal cancer, adenoma, and polyps, respectively.
Results:
Forward MR did not find evidence indicating causal relationship between any of the gut microbiota taxa or six bacterial metabolites tested and colorectal cancer risk. However, reverse MR supported genetic liability to colorectal adenomas was causally related with increased abundance of two taxa: Gammaproteobacteria (β = 0.027, which represents a 0.027 increase in log-transformed relative abundance values of Gammaproteobacteria for per one-unit increase in log OR of adenoma risk; P = 7.06×10−8), Enterobacteriaceae (β = 0.023, P = 1.29×10−5).
Conclusions:
We find genetic liability to colorectal neoplasia may be associated with abundance of certain microbiota taxa. It is more likely that subset of colorectal cancer genetic liability variants changes gut biology by influencing both gut microbiota and colorectal cancer risk.
Impact:
This study highlights the need of future complementary studies to explore causal mechanisms linking both host genetic variation with gut microbiome and colorectal cancer susceptibility.
Associations of Fat Mass and Sarcopenia With All-Cause and Cancer-Specific Mortality in Cancer Survivors
Authors: Aduse-Poku L , Karanth SD , Wheeler M , Yang D , Washington C , Fabregas J , Cheng TYD , Braithwaite D
Published: June 2023

Purpose of the study: The role of body composition in cancer outcomes is of great clinical interest. We investigated whether the risks of all-cause and cancer-specific mortality differ by levels of total fat mass and sarcopenia status in cancer survivors. Methods: Participants included 1682 adult cancer survivors who had undergone dual-energy x-ray absorptiometry (DXA) examination to measure body composition, gathered from the 1999–2006 and 2011–2018 National Health and Nutrition Examination Survey (NHANES). Total fat mass was categorized into tertiles (we assessed high vs. low tertiles), and sarcopenia was defined by appendicular skeletal muscle mass index (females < 5.45 kg/m2 and males < 7.26 kg/m2). Multivariable Cox proportional hazards models were performed to estimate adjusted hazard ratio (aHR) and 95% confidence interval (CI); we also stratified by race. In addition, we performed a restricted cubic spline analysis to assess the potential non-linear association between fat mass and all-cause mortality. Results: The mean age of study participants was 61.9 years, and they were followed up for an average of 9.67 years. Overall, sarcopenia was present in 304 (25.0%), and 561 (33.4%) of the participants had high total fat mass. Participants with higher fat mass had 30% increased risk of all-cause mortality (aHR = 1.30, 95% CI = 1.06–1.61) compared to participants with low fat mass, while participants with sarcopenia had a 51% higher risk (aHR = 1.51, 95% CI = 1.22–1.88) than participants with no sarcopenia. A restricted cubic spline analysis revealed a J-shaped association between fat mass and all-cause mortality. Further, sarcopenia was also associated with a higher risk of cancer-specific mortality (aHR = 1.74, 95% CI = 1.23–2.29) compared to non-sarcopenia. The association between sarcopenia and all-cause mortality was twice as strong in Non-Hispanic Blacks (aHR = 2.99, 95% CI = 1.39–6.06) compared to Non-Hispanic Whites (aHR = 1.53, 95% CI = 1.19–1.95). Conclusion: Our findings show opposing relations of fat mass and appendicular skeletal muscle mass index with mortality in a national sample of cancer survivors, and the relationships may differ by race. These results emphasize the importance of maintaining a healthy body composition among cancer survivors.