bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the diagnosis of severe malaria in African children using platelet counts and plasma
Pf
HRP2 concentrations
Authors: Watson James A. , Uyoga Sophie , Wanjiku Perpetual , Makale Johnstone , Nyutu Gideon M. , Mturi Neema , George Elizabeth C. , Woodrow Charles J. , Day Nicholas P. J. , Bejon Philip , Opoka Robert O. , Dondorp Arjen M. , John Chandy C. , Maitland Kathryn , Williams Thomas N. , White Nicholas J.
Published: July 2022

Severe malaria caused by
Plasmodium falciparum
is difficult to diagnose accurately in children in high-transmission settings. Using data from 2649 pediatric and adult patients enrolled in four studies of severe illness in three countries (Bangladesh, Kenya, and Uganda), we fitted Bayesian latent class models using two diagnostic markers: the platelet count and the plasma concentration of
P. falciparum
histidine-rich protein 2 (
Pf
HRP2). In severely ill patients with clinical features consistent with severe malaria, the combination of a platelet count of ≤150,000/μl and a plasma
Pf
HRP2 concentration of ≥1000 ng/ml had an estimated sensitivity of 74% and specificity of 93% in identifying severe falciparum malaria. Compared with misdiagnosed children, pediatric patients with true severe malaria had higher parasite densities, lower hematocrits, lower rates of invasive bacterial disease, and a lower prevalence of both sickle cell trait and sickle cell anemia. We estimate that one-third of the children enrolled into clinical studies of severe malaria in high-transmission settings in Africa had another cause of their severe illness.
OXA-48-Like β-Lactamases: Global Epidemiology, Treatment Options, and Development Pipeline
Authors: Boyd Sara E. , Holmes Alison , Peck Richard , Livermore David M. , Hope William
Published: July 2022

Modern medicine is threatened by the rising tide of antimicrobial resistance, especially among Gram-negative bacteria, where resistance to β-lactams is most often mediated by β-lactamases. The penicillin and cephalosporin ascendancies were, in their turn, ended by the proliferation of TEM penicillinases and CTX-M extended-spectrum β-lactamases. These class A β-lactamases have long been considered the most important.
Preparation and Testing of Food Freshness Indicators: an Application-Oriented Learning Module Integrating Basic Concepts of Microbiology and Chemistry Laboratory
Authors: Kulkarni Anuttama
Published: July 2022

We describe a novel 4-day food microbiology laboratory learning module for a first-year, introductory undergraduate course. In the module, the students test the suitability of four different pH indicator dyes as freshness indicators for dairy products.
TrmB Family Transcription Factor as a Thiol-Based Regulator of Oxidative Stress Response
Authors: Mondragon Paula , Hwang Sungmin , Kasirajan Lakshmi , Oyetoro Rebecca , Nasthas Angelina , Winters Emily , Couto-Rodriguez Ricardo L. , Schmid Amy , Maupin-Furlow Julie A.
Published: July 2022

TrmB-like proteins, while not yet associated with redox stress, are found in bacteria and widespread in archaea. Here, we expand annotation of a large group of TrmB-like single winged-helix DNA binding domain proteins from diverse archaea to function as thiol-based transcriptional regulators of oxidative stress response.
Glucose-1,6-Bisphosphate, a Key Metabolic Regulator, Is Synthesized by a Distinct Family of α-Phosphohexomutases Widely Distributed in Prokaryotes
Authors: Neumann Niels , Friz Simon , Forchhammer Karl
Published: July 2022

Glc-1,6-BP is known as an essential activator of phosphoglucomutase (PGM) and other members of the αPHM superfamily, making it a central regulator in glycogen metabolism, glycolysis, amino sugar formation as well as bacterial cell wall and capsule formation. Despite this essential role in carbon metabolism, its origin in prokaryotes has so far remained elusive.
Greater Breadth of Vaccine-Induced Immunity in Females than Males Is Mediated by Increased Antibody Diversity in Germinal Center B Cells
Authors: Ursin Rebecca L. , Dhakal Santosh , Liu Hsuan , Jayaraman Sahana , Park Han-Sol , Powell Harrison R. , Sherer Morgan L. , Littlefield Kirsten E. , Fink Ashley L. , Ma Zexu , Mueller Alice L. , Chen Allison P. , Seddu Kumba , Woldetsadik Yishak A. , Gearhart Patricia J. , Larman H. Benjamin , Maul Robert W. , Pekosz Andrew , Klein Sabra L.
Published: July 2022

Adult females develop greater antibody responses to influenza vaccines than males. We hypothesized that female-biased immunity and protection would be dependent on the extent of virus diversity as well as molecular mechanisms in B cells which constrain the breadth of epitope recognition.
Metabolic Phenotyping of Marine Heterotrophs on Refactored Media Reveals Diverse Metabolic Adaptations and Lifestyle Strategies
Authors: Forchielli Elena , Sher Daniel , Segrè Daniel
Published: July 2022

Half of the Earth’s annual primary production is carried out by phytoplankton in the surface ocean. However, this metabolic activity is heavily impacted by heterotrophic bacteria, which dominate the transformation of organic matter released from phytoplankton.
Comparative Plant Transcriptome Profiling of Arabidopsis thaliana Col-0 and Camelina sativa var.CelineInfested with Myzus persicae Aphids Acquiring Circulative and Noncirculative Viruses Reveals Virus- and Plant-Specific Alterations Relevant to Aphid Feeding Behavior and Transmission
Authors: Chesnais Quentin , Golyaev Victor , Velt Amandine , Rustenholz Camille , Brault Véronique , Pooggin Mikhail M. , Drucker Martin
Published: July 2022

Plant viruses change the phenotype of their plant hosts. Some of the changes impact interactions of the plant with insects that feed on the plants and transmit these viruses. These modifications may result in better virus transmission. We examine here the transcriptomes of two plant species infected with two viruses with different transmission modes to work out whether there are plant species-specific and transmission mode-specific transcriptome changes. Our results show that both are the case.
Impact of Phyllosphere
Methylobacterium
on Host Rice Landraces
Authors: Sanjenbam Pratibha , Shivaprasad P. V. , Agashe Deepa
Published: July 2022

Plants are associated with diverse microbes in nature. Do the microbes increase host plant health, and can they be used for agricultural applications? This is an important question that must be answered in the field rather than in the laboratory or greenhouse.
LI-Detector: a Method for Curating Ordered Gene-Replacement Libraries
Authors: Goodall Emily C. A. , Morris Faye C. , McKeand Samantha A. , Sullivan Rudi , Warner Isabel A. , Sheehan Emma , Boelter Gabriela , Icke Christopher , Cunningham Adam F. , Cole Jeffrey A. , Banzhaf Manuel , Bryant Jack A. , Henderson Ian R.
Published: July 2022

The construction of ordered gene replacement libraries requires significant investment of time and resources to create a valuable community resource. During construction, technical errors may result in a limited number of incorrect mutants being made. Such mutants may confound the output of subsequent experiments. Here, using the remarkable
E. coli
Keio knockout library, we describe a method to rapidly validate the construction of every mutant.
Oridonin Attenuates Burkholderia cenocepacia Virulence by Suppressing Quorum-Sensing Signaling
Authors: Li Xia , Wang Kai , Wang Gerun , Cui Binbin , Song Shihao , Sun Xiuyun , Deng Yinyue
Published: July 2022

Burkholderia cenocepaciais an important human opportunistic pathogen that can cause life-threatening infections in susceptible individuals. It employs quorum-sensing (QS) systems to regulate biological functions and virulence.
Kaempferol-Driven Inhibition of Listeriolysin O Pore Formation and Inflammation Suppresses Listeria monocytogenes Infection
Authors: Wang Tingting , Liu Baichen , Zhang Can , Fang Tianqi , Ding Ying , Song Ge , Zhang Siqi , Shi Linlin , Deng Xuming , Wang Jianfeng
Published: July 2022

Currently, we are facing a global crisis of antibiotic resistance, and novel alternative approaches are urgently needed to curb
L. monocytogenes
infection. Our study demonstrated that kaempferol alleviated
L. monocytogenes
infection via suppressing LLO pore formation and inflammation response, which might represent a novel antimicrobial-independent strategy to curb listeriosis.
Clinical and Genomic Epidemiology of
mcr-9
-Carrying Carbapenem-Resistant
Enterobacterales
Isolates in Metropolitan Atlanta, 2012 to 2017
Authors: Babiker Ahmed , Bower Chris , Lutgring Joseph D. , Petit Robert A. , Howard-Anderson Jessica , Ansari Uzma , McAllister Gillian , Adamczyk Michelle , Breaker Erin , Satola Sarah W. , Jacob Jesse T. , Woodworth Michael H.
Published: July 2022

Colistin is a last-resort antibiotic for multidrug-resistant Gram-negative infections. A recently described allele of the mobile colistin resistance (
mcr
) gene family, designated
mcr-9,
has been widely reported among
Enterobacterales
species.
Malignant gastrointestinal neuroectodermal tumour arising in the extrahepatic bile ducts; a rare neoplasm in an unusual anatomic location
Authors: Miller C Quinn , Al-Hader Ahmad , Vance Gail H , Zhang Chen
Published: July 2022

Malignant gastrointestinal neuroectodermal tumour (GNET) is a rare, aggressive neoplasm with fewer than 100 cases reported in the literature. Most cases arise in the tubular gastrointestinal tract. We reported a unique case of GNET arising in the extrahepatic bile ducts and reviewed the literature of GNETs. The patient is a female in her mid-30s who presented with painless jaundice and diarrhoea several months after cholecystectomy for biliary dyskinesia. Workup revealed a tumour arising from the peripheral 4B bile ducts involving the left hepatic duct and bifurcation. Histologic examination of the lesion showed a malignant spindled and epithelioid neoplasm which strongly expressed S100 and SOX-10. Neoplastic cells were negative for various cytokeratins and melanoma markers. FISH testing usingEWSR1break-apart probes showed rearrangement of theEWSR1gene region. The immunohistochemical and molecular findings are consistent with a diagnosis of GNET arising in the extrahepatic bile ducts.
Relationship between obesity indicators and hypertension–diabetes comorbidity among adults: a population study from Central China
Authors: Wu Wenwen , Wu Yifan , Yang Jinru , Sun Donghan , Wang Ying , Ni Ziling , Yang Fen , Xie Yaofei , Tan Xiaodong , Li Ling , Li Li
Published: July 2022

Objective

To identify the relationship between obesity indicators and hypertension–diabetes comorbidity (HDC) among adults in central China.

Design and setting

A cross-sectional study was conducted from 1 June 2015 to 30 September 2018 in 11 districts of Hubei Province, China.

Participants

A total of 29 396 participants aged 18 years or above were enrolled in the study. 2083 subjects with missing data were excluded. Eventually, 25 356 participants were available for the present analysis.

Main outcome measures

Data were subjected to univariable and multivariable logistic regression to examine the association between obesity indicators (body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR)) and HDC prevalence. Crude odds ratio and adjusted OR (AOR) with associated 95% CI were calculated.

Results

Overall, 2.8% of the respondents had HDC. The odds of HDC prevalence increased with the BMI of the participants (18.5≤BMI (kg/m2)≤23.9—1; 24≤BMI (kg/m2)≤26.9—AOR: 5.66, 95% CI: 4.25 to 7.55; BMI (kg/m2)≥27—AOR: 7.96, 95% CI: 5.83 to 10.87). The risk of HDC also increased with the WHtR of participants (WHtR≤P25—1; P25≤WHtR≤P50—AOR: 1.73, 95% CI: 1.10 to 2.71; P50 ≤WHtR≤P75—AOR: 2.51, 95% CI: 1.60 to 3.92; WHtR≥P75—AOR: 3.22, 95% CI: 2.01 to 5.16). Stratified analysis by gender showed that high BMI and WHtR were risk factors of HDC in males and females. However, the odds of HDC prevalence increased only when WHtR≥P75 in males, whereas the probability of HDC increased when WHtR≥ P25 in females.

Conclusion

High BMI and WHtR can increase the risk of HDC among Chinese adults. Reasonable control of BMI and WHtR may be beneficial in preventing HDC. Females should focus on maintaining an optimal WHtR earlier.
Longitudinal impact of preregistration interprofessional education on the attitudes and skills of health professionals during their early careers: a non-randomised trial with 4-year outcomes
Authors: Darlow Ben , Brown Melanie , McKinlay Eileen , Gray Lesley , Purdie Gordon , Pullon Sue
Published: July 2022

Objective

To assess whether a preregistration interprofessional education (IPE) programme changed attitudes towards teamwork and team skills during health professionals’ final year of training and first 3 years of professional practice.

Design

Prospective, longitudinal, non-randomised trial.

Setting

Final year health professional training at three academic institutions in New Zealand.

Participants

Students from eight disciplines eligible to attend the IPE programme were recruited (617/730) prior to their final year of training. 130 participants attended the IPE programme; 115 intervention and 372 control participants were included in outcome analysis.

Intervention

The 5-week Tairāwhiti IPE (TIPE) immersion programme during which students experience clinical placements in interdisciplinary teams, complete collaborative tasks and live together in shared accommodation.

Main outcome measures

Data were collected via five surveys at 12-month intervals, containing Attitudes Towards Healthcare Teams Scale (ATHCTS), Team Skills Scale (TSS) and free-text items. Mixed-model analysis of covariance, adjusting for baseline characteristics, compared scores between groups at each time point. Template analysis identified themes in free-text data.

Results

Mean ATHCTS scores for TIPE participants were 1.4 (95% CI 0.6 to 2.3) points higher than non-TIPE participants (p=0.002); scores were 1.9 (95% CI 0.8 to 3.0) points higher at graduation and 1.1 (95% CI −0.1 to 2.4) points higher 3 years postgraduation. Mean TSS scores for TIPE participants were 1.7 (95% CI 0.0 to 3.3) points higher than non-TIPE participants (p=0.045); scores were 3.5 points (95% CI 1.5 to 5.5) higher at graduation and 1.3 (95%CI −0.8 to 3.5) points higher 3 years postgraduation. TIPE participants made substantially more free-text comments about benefits of interprofessional collaboration and perceived the TIPE programme had a meaningful influence on their readiness to work in teams and the way in which they performed their healthcare roles.

Conclusions

TIPE programme participation significantly improved attitudes towards healthcare teams and these changes were maintained over 4 years.
Evaluating the impact of a multicountry interprofessional training programme to improve HIV knowledge and clinical confidence among healthcare workers in sub-Saharan Africa: a cohort study
Authors: Kiguli-Malwadde Elsie , Forster Maeve , Martin Shayanne , Chilemba Evelyn , Couper Ian , Motlhatlhedi Keneilwe , Celentano Jessica , Haruzivishe Clara , Sears David , Budak Jehan Z , Khanyola Judy N. , Von Zinkernagel Deborah , Molwantwa Mmoloki , Semitala Fred , de Villiers Marietjie , Reid Michael , Kazembe Abigail
Published: July 2022

Objective

To assess the impact of an interprofessional case-based training programme to enhance clinical knowledge and confidence among clinicians working in high HIV-burden settings in sub-Saharan Africa (SSA).

Setting

Health professions training institutions and their affiliated clinical training sites in 12 high HIV-burden countries in SSA.

Participants

Cohort comprising preservice and in-service learners, from diverse health professions, engaged in HIV service delivery.

Intervention

A standardised, interprofessional, case-based curriculum designed to enhance HIV clinical competency, implemented between October 2019 and April 2020.

Main outcome measures

The primary outcomes measured were knowledge and clinical confidence related to topics addressed in the curriculum. These outcomes were assessed using a standardised online assessment, completed before and after course completion. A secondary outcome was knowledge retention at least 6 months postintervention, measured using the same standardised assessment, 6 months after training completion. We also sought to determine what lessons could be learnt from this training programme to inform interprofessional training in other contexts.

Results

Data from 3027 learners were collected: together nurses (n=1145, 37.9%) and physicians (n=902, 29.8%) constituted the majority of participants; 58.1% were preservice learners (n=1755) and 24.1% (n=727) had graduated from training within the prior year. Knowledge scores were significantly higher, postparticipation compared with preparticipation, across all content domains, regardless of training level and cadre (all p<0.05). Among 188 learners (6.2%) who retook the test at >6 months, knowledge and self-reported confidence scores were greater compared with precourse scores (all p<0.05).

Conclusion

To our knowledge, this is the largest interprofessional, multicountry training programme established to improve HIV knowledge and clinical confidence among healthcare professional workers in SSA. The findings are notable given the size and geographical reach and demonstration of sustained confidence and knowledge retention post course completion. The findings highlight the utility of interprofessional approaches to enhance clinical training in SSA.
Delphi study to identify consensus on patient selection for hydrogel rectal spacer use during radiation therapy for prostate cancer in the UK
Authors: Payne Heather Ann , Jain Suneil , Peedell Clive , Edwards Albert , Thomas James Andrew , Das Prantik , Hansson Hedblom Amanda , Woodward Emily , Saunders Rhodri , Bahl Amit
Published: July 2022

Objectives

To identify consensus on patient prioritisation for rectal hydrogel spacer use during radiation therapy for the treatment of prostate cancer in the UK.

Design

Delphi study consisting of two rounds of online questionnaires, two virtual advisory board meetings and a final online questionnaire.

Setting

Radical radiation therapy for localised and locally advanced prostate cancer in the UK.

Participants

Six leading clinical oncologists and one urologist from across the UK.

Interventions

Rectal hydrogel spacer.

Primary and secondary outcome measures

None reported.

Results

The panel reached consensus on the importance of minimising toxicity for treatments with curative intent and that even low-grade toxicity-related adverse events can significantly impact quality of life. There was agreement that despite meeting rectal dose constraints, too many patients experience rectal toxicity and that rectal hydrogel spacers in eligible patients significantly reduces toxicity-related adverse events. However, as a consequence of funding limitations, patients need to be prioritised for spacer use. A higher benefit of spacers can be expected in patients on anticoagulation and in patients with diabetes or inflammatory bowel disease, but consensus could not be reached regarding patient groups expected to benefit less. While radiation therapy regimen is not a main factor determining prioritisation, higher benefit is expected in ultrahypofractionated regimens.

Conclusion

There is a strong and general agreement that all patients with prostate cancer undergoing radical radiation therapy have the potential to benefit from hydrogel spacers. Currently, not all patients who could potentially benefit can access hydrogel spacers, and access is unequal. Implementation of the consensus recommendations would likely help prioritise and equalise access to rectal spacers for patients in the UK.
Protocol for a qualitative study to explore acceptability, barriers and facilitators of the implementation of new teleophthalmology technologies between community optometry practices and hospital eye services
Authors: Blandford Ann , Abdi Sarah , Aristidou Angela , Carmichael Josie , Cappellaro Giulia , Hussain Rima , Balaskas Konstantinos
Published: July 2022

Introduction

Novel teleophthalmology technologies have the potential to reduce unnecessary and inaccurate referrals between community optometry practices and hospital eye services and as a result improve patients’ access to appropriate and timely eye care. However, little is known about the acceptability and facilitators and barriers to the implementations of these technologies in real life.

Methods and analysis

A theoretically informed, qualitative study will explore patients’ and healthcare professionals’ perspectives on teleophthalmology and Artificial Intelligence Decision Support System models of care. A combination of situated observations in community optometry practices and hospital eye services, semistructured qualitative interviews with patients and healthcare professionals and self-audiorecordings of healthcare professionals will be conducted. Participants will be purposively selected from 4 to 5 hospital eye services and 6–8 affiliated community optometry practices. The aim will be to recruit 30–36 patients and 30 healthcare professionals from hospital eye services and community optometry practices. All interviews will be audiorecorded, with participants’ permission, and transcribed verbatim. Data from interviews, observations and self-audiorecordings will be analysed thematically and will be informed by normalisation process theory and an inductive approach.

Ethics and dissemination

Ethical approval has been received from London-Bromley research ethics committee. Findings will be reported through academic journals and conferences in ophthalmology, health services research, management studies and human-computer interaction.
COVID-19 and children with congenital anomalies: a European survey of parents’ experiences of healthcare services
Authors: Latos-Bieleńska Anna , Marcus Elena , Jamry-Dziurla Anna , Rankin Judith , Barisic Ingeborg , Cavero- Carbonell Clara , Den Hond Elly , Garne Ester , Genard Lucas , João Santos Ana , Lutke L Renée , Matias Dias Carlos , Neergaard Pedersen Christina , Neville Amanda , Niemann Annika , Odak Ljubica , Páramo-Rodríguez Lucía , Pierini Anna , Rissmann Anke , Morris Joan K
Published: July 2022

Objective

To survey parents and carers of children with a congenital anomaly across Europe about their experiences of healthcare services and support during the COVID-19 pandemic.

Design

Cross-sectional study.

Setting

Online survey in 10 European countries, open from 8 March 2021 to 14 July 2021.

Population

1070 parents and carers of children aged 0–10 years with a cleft lip, spina bifida, congenital heart defect (CHD) requiring surgery and/or Down syndrome.

Main outcome measures

Parental views about: the provision of care for their child (cancellation/postponement of appointments, virtual appointments, access to medication), the impact of disruptions to healthcare on their child’s health and well-being, and satisfaction with support from medical sources, organisations and close relationships.

Results

Disruptions to healthcare appointments were significantly higher (p<0.001) in the UK and Poland, with approximately two-thirds of participants reporting ‘cancelled or postponed’ tests (67/101; 256/389) and procedures compared with approximately 20% in Germany (13/74) and Belgium/Netherlands (11/55). A third of participants in the UK and Poland reported ‘cancelled or postponed’ surgeries (22/72; 98/266) compared with only 8% in Germany (5/64). In Poland, 43% (136/314) of parents reported that changes to their child’s ongoing treatment had moderately to severely affected their child’s health, significantly higher than all other countries (p<0.001). Satisfaction ratings for support from general practitioners were lowest in the UK and Poland, and lowest in Poland and Italy for specialist doctors and nurses.

Conclusion

A large proportion of participants reported disruptions to healthcare during the pandemic, which for some had a significant impact on their child’s health. Regional differences in disruptions raise questions about the competence of certain healthcare systems to meet the needs of this vulnerable group of patients and indicate improvements should be strived for in some regions.
Prevalence of intestinal parasites and associated factors among food handlers in food establishments in the Lideta subcity of Addis Ababa, Ethiopia: an institution-based, cross-sectional study
Authors: Abera Woinishet , Gintamo Binyam , Shitemaw Tewoderos , Mekuria Zelalem Negash , Gizaw Zemichael
Published: July 2022

Objective

This study was conducted to assess the prevalence of intestinal parasites and the associated factors among food handlers in the Lideta subcity of Addis Ababa, Ethiopia.

Design

An institution-based, cross-sectional study design was used. Stool samples were collected from food handlers and examined using direct wet mount and formalin-ether concentration techniques. Personal and establishment-related information was collected using a pretested questionnaire, with a structured observation. Multivariable binary logistic regression was used to identify factors associated with the prevalence of intestinal parasites on the basis of adjusted OR (AOR) and 95% CI and p values <0.05.

Setting

Food establishments in the Lideta subcity of Addis Ababa, Ethiopia.

Participants

411 food handlers participated in the study.

Outcome measures

The primary outcome was the prevalence of intestinal parasites, defined as the presence of one or more intestinal parasitic species in stool samples.

Results

One or more intestinal parasites were detected in 171 (41.6%; 95% CI 36.6% to 46.4%) stool samples. The most common intestinal parasites were Entamoeba histolytica/dispar (12.7%), Giardia duodenalis (11.2%) and Ascaris lumbricoides (8.3%). The presence of intestinal parasites among food handlers was associated with low monthly income (AOR: 2.83, 95% CI 1.50 to 8.84), untrimmed fingernails (AOR: 4.36, 95% CI 1.98 to 11.90), no food safety training (AOR: 2.51, 95% CI 1.20 to 5.58), low level of education (AOR: 3.13, 95% CI 1.34 to 7.44), poor handwashing practice (AOR: 2.16, 95% CI 1.03 to 4.22) and lack of medical check-up (AOR: 2.31, 95% CI 1.18 to 6.95).

Conclusion

The prevalence of intestinal parasites among food handlers in food establishments in the Lideta subcity of Addis Ababa was high. The presence of intestinal parasites was linked to socioeconomic conditions, poor hand hygiene conditions and absence of food safety training. It is crucially important to promote handwashing practices and provide food hygiene and safety training in these settings.
Prevalence and determinants of atrial fibrillation progression in paroxysmal atrial fibrillation
Authors: Nguyen Bao-Oanh , Weberndorfer Vanessa , Crijns Harry JGM , Geelhoed Bastiaan , Ten Cate Hugo , Spronk Henri , Kroon Abraham , De With Ruben , Al-Jazairi Meelad , Maass Alexander H , Blaauw Yuri , Tieleman Robert G , Hemels Martin E W , Luermans Justin , de Groot Joris , Allaart Cornelis P , Elvan Arif , De Melis Mirko , Scheerder Coert , van Zonneveld Anton Jan , Schotten Ulrich , Linz Dominik , Van Gelder Isabelle , Rienstra Michiel
Published: July 2022

Objective

Atrial fibrillation (AF) often progresses from paroxysmal AF (PAF) to more permanent forms. To improve personalised medicine, we aim to develop a new AF progression risk prediction model in patients with PAF.

Methods

In this interim-analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF study, patients with PAF undergoing extensive phenotyping at baseline and continuous rhythm monitoring during follow-up of ≥1 year were analysed. AF progression was defined as (1) progression to persistent or permanent AF or (2) progression of PAF with >3% burden increase. Multivariable analysis was done to identify predictors of AF progression.

Results

Mean age was 65 (58–71) years, 179 (43%) were female. Follow-up was 2.2 (1.6–2.8) years, 51 of 417 patients (5.5%/year) showed AF progression. Multivariable analysis identified, PR interval, impaired left atrial function, mitral valve regurgitation and waist circumference to be associated with AF progression. Adding blood biomarkers improved the model (C-statistic from 0.709 to 0.830) and showed male sex, lower levels of factor XIIa:C1-esterase inhibitor and tissue factor pathway inhibitor, and higher levels of N-terminal pro-brain natriuretic peptide, proprotein convertase subtilisin/kexin type 9 and peptidoglycan recognition protein 1 were associated with AF progression.

Conclusion

In patients with PAF, AF progression occurred in 5.5%/year. Predictors for progression included markers for atrial remodelling, sex, mitral valve regurgitation, waist circumference and biomarkers associated with coagulation, inflammation, cardiomyocyte stretch and atherosclerosis. These prediction models may help to determine risk of AF progression and treatment targets, but validation is needed.

Trial registration number

NCT02726698.
Suicidal ideation and suicide attempts among older recipients of public welfare assistance in Japan
Authors: Kino Shiho , Stickley Andrew , Nishioka Daisuke , Ueno Keiko , Saito Masashige , Ojima Toshiyuki , Kondo Naoki
Published: July 2022

Background

The high suicide rate among older adults is an important public health issue. Financial insecurity has been linked to suicidal behaviour. Despite this, as yet, there has been little research on suicide-related behaviours among older recipients of public welfare. This study will examine if suicidal ideation and suicide attempts are more prevalent in older recipients of public welfare assistance in Japan.

Methods

This cross-sectional study analysed data from 16 135 adults aged ≥65 years who participated in the 2019 wave of the Japan Gerontological Evaluation Study. Information was obtained on receiving public welfare assistance, lifetime suicidal ideation and attempts, and a variety of covariates. Poisson regression analysis with robust variance estimates was used to examine associations.

Results

Suicidal ideation was reported by 4.8% of the participants, while the corresponding figure for attempted suicide was 2.2%. In fully adjusted analyses public welfare recipients had an almost 1.5 times higher prevalence of lifetime suicidal ideation (prevalence ratio, PR 1.47, 95% CI 1.02 to 2.13), and an almost two times higher prevalence of attempted suicide (PR 1.91, 95% CI 1.20 to 3.04) when compared with their counterparts not receiving public welfare assistance.

Conclusion

Older recipients of public welfare have a higher prevalence of suicidal behaviour in Japan. An urgent focus is now warranted on this vulnerable population to determine the specific factors underlying this association.
Acute Myocardial Infarction and Concomitant Acute Intracranial Hemorrhage: Clinical Characteristics and Outcomes
Authors: Cao Xiangqi , Wei Meng , Tang Manyun , Jian Zhijie , Liu Hui , Yue Xin , Luo Guogang , Sun Chaofeng , Guo Fengwei
Published: July 2022

This study aimed to evaluate the demographic and clinical characteristics, treatments and outcomes of concomitant acute myocardial infarction (AMI) and acute intracranial hemorrhage (ICH). All patients diagnosed with concomitant AMI and acute ICH admitted to our institution were included retrospectively. The patient demographics, clinical characteristics, neuroimaging and treatment approaches were analyzed, and the outcomes of interest included disability as defined by the modified Rankin Scale (mRS) score and all-cause mortality within 1 year of follow-up. Of a total of 4972 patients with AMI, 8 patients (0.2%) with concomitant acute ICH were recruited for the study, including ST-segment elevation myocardial infarction (STEMI, 5 cases) and non-STEMI (3 cases). New-onset acute ICH in 4 of the 5 patients (80%) occurred within 24 hours after the AMI event, and all these patients had a sudden decrease in the level of consciousness, with an average decrease of 4.6 on the Glasgow Coma Scale. All 5 out of 8 patients had irregular shapes and uncommon sites of hematoma presentation documented on CT scans. Unfortunately, 2 patients died from a progression of ICH within 1 week, and 2 of the 6 survivors had poor functional outcomes (mRS ≥3) at the 1-year follow-up. Concomitant acute ICH and AMI are rare complications displaying unique iconography. Acute ICH caused serious prejudice in AMI with higher mortality and poor functional outcomes, and cardiac catheterization without the administration of antithrombotic or antiplatelet agents was feasible for patients who had unstable hemodynamics or STEMI.
Colocalized targeting of TGF-β and PD-L1 by bintrafusp alfa elicits distinct antitumor responses
Authors: Lan Yan , Yeung Tsz-Lun , Huang Hui , Wegener Ansgar A , Saha Somdutta , Toister-Achituv Mira , Jenkins Molly H , Chiu Li-Ya , Lazorchak Adam , Tarcic Ohad , Wang Hong , Qi Jin , Locke George , Kalimi Doron , Qin Guozhong , Marelli Bo , Yu Huakui , Gross Alec W , Derner Melissa G , Soloviev Maria , Botte Mathieu , Sircar Aroop , Ma Hong , Sood Vanita D , Zhang Dong , Jiang Feng , Lo Kin-Ming
Published: July 2022

Background

Bintrafusp alfa (BA) is a bifunctional fusion protein designed for colocalized, simultaneous inhibition of two immunosuppressive pathways, transforming growth factor-β (TGF-β) and programmed death-ligand 1 (PD-L1), within the tumor microenvironment (TME). We hypothesized that targeting PD-L1 to the tumor by BA colocalizes the TGF-β trap (TGF-βRII) to the TME, enabling it to sequester TGF-β in the tumor more effectively than systemic TGF-β blockade, thereby enhancing antitumor activity.

Methods

Multiple technologies were used to characterize the TGF-β trap binding avidity. BA versus combinations of anti-PD-L1 and TGF-β trap or the pan-TGF-β antibody fresolimumab were compared in proliferation and two-way mixed lymphocyte reaction assays. Immunophenotyping of tumor-infiltrating lymphocytes (TILs) and RNA sequencing (RNAseq) analysis assessing stromal and immune landscape following BA or the combination therapy were performed in MC38 tumors. TGF-β and PD-L1 co-expression and their associated gene signatures in MC38 tumors and human lung carcinoma tissue were studied with single-cell RNAseq (scRNAseq) and immunostaining. BA-induced internalization, degradation, and depletion of TGF-β were investigated in vitro.

Results

BA and fresolimumab had comparable intrinsic binding to TGF-β1, but there was an ~80× avidity-based increase in binding affinity with BA. BA inhibited cell proliferation in TGF-β-dependent and PD-L1-expressing cells more potently than TGF-β trap or fresolimumab. Compared with the combination of anti-PD-L1 and TGF-β trap or fresolimumab, BA enhanced T cell activation in vitro and increased TILs in MC38 tumors, which correlated with efficacy. BA induced distinct gene expression in the TME compared with the combination therapy, including upregulation of immune-related gene signatures and reduced activities in TGF-β-regulated pathways, such as epithelial-mesenchymal transition, extracellular matrix deposition, and fibrosis. Regulatory T cells, macrophages, immune cells of myeloid lineage, and fibroblasts were key PD-L1/TGF-β1 co-expressing cells in the TME. scRNAseq analysis suggested BA modulation of the macrophage phenotype, which was confirmed by histological assessment. PD-L1/TGF-β1 co-expression was also seen in human tumors. Finally, BA induced TGF-β1 internalization and degradation in the lysosomes.

Conclusion

BA more effectively blocks TGF-β by targeting TGF-β trap to the tumor via PD-L1 binding. Such colocalized targeting elicits distinct and superior antitumor responses relative to single agent combination therapy.
ELK3 modulates the antitumor efficacy of natural killer cells against triple negative breast cancer by regulating mitochondrial dynamics
Authors: Park Joo Dong , Kim Kwang-Soo , Choi Seung Hee , Jo Gae Hoon , Choi Jin-Ho , Park Si-Won , Ko Eun-Su , Lee Minwook , Lee Dae-Keum , Jang Hye Jung , Hwang Sohyun , Jung Hae-Yun , Park Kyung-Soon
Published: July 2022

Background

Triple negative breast cancer (TNBC) is the most lethal subtype of breast cancer due to its aggressive behavior and frequent development of resistance to chemotherapy. Although natural killer (NK) cell-based immunotherapy is a promising strategy for overcoming barriers to cancer treatment, the therapeutic efficacy of NK cells against TNBC is below expectations. E26 transformation-specific transcription factor ELK3 (ELK3) is highly expressed in TNBCs and functions as a master regulator of the epithelial-mesenchymal transition.

Methods

Two representative human TNBC cell lines, MDA-MB231 and Hs578T, were exposed to ELK3-targeting shRNA or an ELK3-expressing plasmid to modulate ELK3 expression. The downstream target genes of ELK3 were identified using a combined approach comprising gene expression profiling and molecular analysis. The role of ELK3 in determining the immunosensitivity of TNBC to NK cells was investigated in terms of mitochondrial fission–fusion transition and reactive oxygen species concentration both in vitro and in vivo.

Results

ELK3-dependent mitochondrial fission–fusion status was linked to the mitochondrial superoxide concentration in TNBCs and was a main determinant of NK cell-mediated immune responses. We identified mitochondrial dynamics proteins of 51 (Mid51), a major mediator of mitochondrial fission, as a direct downstream target of ELK3 in TNBCs. Also, we demonstrated that expression of ELK3 correlated inversely with that of Mid51, and that the ELK3-Mid51 axis is associated directly with the status of mitochondrial dynamics. METABRIC analysis revealed that the ELK3-Mid51 axis has a direct effect on the immune score and survival of patients with TNBC.

Conclusions

Taken together, the data suggest that NK cell responses to TNBC are linked directly to ELK3 expression levels, shedding new light on strategies to improve the efficacy of NK cell-based immunotherapy of TNBC.
Teaching poster design to enhance research presentation quality at academic conferences: a guide for educators
Authors: Belilos Eleanor , Kamande Stanley , Morrison Mike , Malmut Laura
Published: July 2022

Poster sessions are one of the most common platforms for presenting research at academic conferences, yet posters are often inefficient at transferring knowledge to their readers due to suboptimal design and content selection. Physician trainees may not receive education on constructing posters as a traditional part of their residency curriculum. The purpose of this work is to propose a curriculum that will provide residents foundational knowledge and skills needed for designing high-quality research posters. The curriculum uses the flipped classroom model, a pedagogical approach that reverses the traditional learning environment by delivering instructional content outside of the classroom and moves activities into the classroom. Preparatory work includes watching an educational video on ‘how to create a better research poster in less time’ and preparing a poster to be presented at an upcoming conference. An 1-hour workshop is conducted during protected resident didactic time. It incorporates a 10-min slide show presentation on poster design and 50 min of active learning. During the active learning component, learners are asked to ‘think–pair–share’ to construct a research poster rubric using the information they just learnt. The learners work as a group to evaluate sample research posters. The class is then broken down into small groups of 2–3 learners to spend time working on their own posters and provide peer feedback. Following the workshop, residents continue to develop their research posters for conference presentation. This curriculum has the potential to enhance the quality of resident research posters presented at academic conferences, advance research education and ultimately improve dissemination of research within academic communities. The lesson plan outlined in this work can be used as a guide for teaching poster design to physician trainees in a number of specialties and may encourage programmes to consider integrating poster design as a formal part of the residency curriculum.

Research questions
Impact of varying degrees of peripheral nerve blockade on experimental pressure and ischemic pain: adductor canal and sciatic nerve blocks in a human model of compartment syndrome pain
Authors: Chen Yun-Yun Kathy , Lirk Philipp , Flowers K Mikayla , Colebaugh Carin A , Wilson Jenna M , Zeballos Jose , Von Keudell Arvind , Barrett Karyn E , Vlassakov Kamen , Schreiber Kristin L
Published: July 2022

Introduction

Early diagnosis of acute extremity compartment syndrome is crucial to timely surgical management. Pain is commonly used as an early diagnostic sign for acute extremity compartment syndrome, making regional anesthesia after lower extremity surgery controversial. This randomized study tested whether different concentrations of local anesthetics, or combinations of nerve blocks, would differentially impact the perception of acute extremity compartment syndrome-like pressure and ischemic pain.

Methods

Healthy volunteers underwent quantitative sensory testing, including determination of pressure pain thresholds and prolonged pressure/ischemic pain in the leg using a variable cuff inflation system. Subjects were randomized to receive (1) adductor canal block alone (ACB), (2) ACB with low-concentration sciatic nerve block (ACB +LC SNB), or (3) ACB with high-concentration SNB (ACB +HC SNB). For the primary outcome, we assessed block-induced increases in pressure threshold to reach 6/10 pain, and compared the degree of increase between the three groups. The main secondary outcome was a comparison of average pain score during a 5 min hold at the 6/10 pressure pain threshold between the three groups.

Results

All blocks raised pressure pain threshold and decreased ischemic pain, but to variable extents. Specifically, the amount the block increased pressure pain threshold was significantly different among ACB, ACB+LC SNB, and ACB+HC SNB groups (mean±SD: 24±32 mm Hg, 120±103 mm Hg, 159±93 mm Hg; p=0.002), with post hoc testing revealing ACB as less than the other two groups. Similarly, average pain scores during a prolonged/ischemic cuff hold differed among the groups (4.2±1.4, 1.4±1.7, 0.4±0.7; p<0.001), with post hoc testing revealing ACB as significantly higher.

Discussion

This study suggests the possible utility of titrating regional anesthesia, to provide some analgesia while still allowing acute extremity compartment syndrome detection.

Trial registration number

NCT04113954.
Laparoscopic management of benign splenic tumors in children
Authors: Qingjiang Chen , Wang Linyan , Chen Xiaoli , Zhang Yuebin , Zhang Lifeng , Zhu Kun , Xiong Qixing , Gao Zhigang
Published: July 2022

Background

The splenic tumor is relatively rare in children. However, diagnosing and managing this disease remain controversial. This study aimed to evaluate the clinical characteristics and pathological features of benign splenic tumors and to explore the feasibility and safety of laparoscopic splenectomy in children.

Methods

The clinical data of all patients who were diagnosed with benign splenic tumors and admitted to our center between January 2014 and December 2020 were analyzed retrospectively. Factors that were documented included demographic criteria, clinical manifestations, preoperative examinations, surgical methods, histopathological characteristics, postoperative complications and outcomes.

Results

Totally, 24 consecutive patients with a mean age of 10.21±2.59 years were operated laparoscopically. Nine patients presented with recurrent abdominal pain, vomiting or backache. The remaining 15 cases were asymptomatic and were identified incidentally. Laparoscopic total splenectomy (LTS) was performed in 12 cases, laparoscopic partial splenectomy (LPS) in 9 cases and deroofing of splenic cyst in 3 cases. No significant differences were observed in operation time, intraoperative bleeding and postoperative abdominal drainage between the LTS and LPS groups. Histopathology examination reported 12 cases of splenic epithelial cyst, 5 cases of splenic lymphangioma or lymphatic malformation, 3 cases of splenic hamartoma, 3 cases of splenic littoral cell angioma and 1 case of splenic hemangioma. No postoperative complications and tumor recurrence were observed.

Conclusions

It is still difficult to precisely diagnose the splenic tumor preoperatively. Laparoscopic splenectomy is safe and feasible in treating the benign splenic tumors, and partial splenectomy is of great significance in preserving the immune function in children.
Paleomagnetism of the Grum Zn–Pb–Ag deposit, Selwyn Basin, Yukon, Canada
Authors: Kawasaki Kazuo , Symons David T.A.
Published: July 2022

The Grum deposit is one of five large clastic-dominated Zn–Pb–Ag deposits in the Anvil district of the Selwyn Basin, Yukon. Grum's mineralization occurs at the contact between the late Proterozoic to Cambrian Mount Mye Formation and the Cambrian to Early Ordovician Vangorda Formation. Paleomagnetic analyses of 113 specimens from 15 mineralized sites in the Grum open pit were undertaken to date Grum's mineralization. The analyses isolated a stable characteristic remanent magnetization (ChRM), mostly by thermal and then alternating field demagnetization. The main ChRM carrier is single- or pseudosingle-domain pyrrhotite with minor magnetite that give a paleopole at 67.8°N latitude and 317.4°E longitude (radius of the cone of 95% confidence, A95 = 7.2°). The paleopole yields an age of 176 ± 12 Ma for the Grum deposit after a clockwise rotation and northward translation of the basin to best fit the North American apparent polar wander path. Thus, the Zn–Pb–Ag Grum mineralization significantly predates intrusion of the nearby mid-Cretaceous Anvil Batholith, but is coeval with widespread Early Jurassic metamorphism in the Selwyn Basin that correlates with the Early Jurassic collision of the Intermontane Belt terranes with the North America craton.
The role of drought stress on the acquisition of freezing tolerance in asparagus under controlled conditions
Authors: Short William , Wolyn David J.
Published: July 2022

Cold acclimation induces freezing tolerance in asparagus ( Asparagus officinalis L.), which is important for survival and longevity in temperate climates. Previous studies indicated that cultivar “Guelph Millennium” (GM), adapted to Southern Ontario, acquired freezing tolerance earlier in the fall and maintained it later in the spring than “UC157” (UC), a cultivar commonly grown in desert climates. As the drought and cold acclimation metabolic pathways overlap, the objective of this research was to determine whether drought alone induced freezing tolerance or interacted synergistically with cold temperatures. Seedlings of GM and UC were subjected to control, drought, or cold acclimating conditions for 6 weeks. Additional treatments included 6 weeks of drought or control conditions followed by 6 weeks of cold acclimation, and plants grown for 12 weeks under control conditions. LT50, the temperature at which 50% of plants die, and metabolites or parameters associated with freezing tolerance were measured. GM had decreased LT50 levels (increased freezing tolerance) compared with UC under both drought and cold acclimating conditions, and no cultivar differences were observed under control conditions. Drought stress before cold acclimation resulted in an increased LT50 (reduced freezing tolerance) for UC compared with GM. A high root:shoot ratio and low crown water percentage were associated with increased freezing tolerance in GM, while a high crown sucrose concentration in UC was related to decreased freezing tolerance for the drought treatment. Overall, drought stress induced cultivar-specific adaptations causing differences in freezing tolerance, thus confirming the interrelationship between these two physiological pathways.