bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial intelligence in clinical and translational science: Successes, challenges and opportunities
Authors: Bernstam Elmer V. , Shireman Paula K. , Meric‐Bernstam Funda , N. Zozus Meredith , Jiang Xiaoqian , Brimhall Bradley B. , Windham Ashley K. , Schmidt Susanne , Visweswaran Shyam , Ye Ye , Goodrum Heath , Ling Yaobin , Barapatre Seemran , Becich Michael J.
Published: October 2021

Artificial intelligence (AI) is transforming many domains, including finance, agriculture, defense, and biomedicine. In this paper, we focus on the role of AI in clinical and translational research (CTR), including preclinical research (T1), clinical research (T2), clinical implementation (T3), and public (or population) health (T4). Given the rapid evolution of AI in CTR, we present three complementary perspectives: (1) scoping literature review, (2) survey, and (3) analysis of federally funded projects. For each CTR phase, we addressed challenges, successes, failures, and opportunities for AI. We surveyed Clinical and Translational Science Award (CTSA) hubs regarding AI projects at their institutions. Nineteen of 63 CTSA hubs (30%) responded to the survey. The most common funding source (48.5%) was the federal government. The most common translational phase was T2 (clinical research, 40.2%). Clinicians were the intended users in 44.6% of projects and researchers in 32.3% of projects. The most common computational approaches were supervised machine learning (38.6%) and deep learning (34.2%). The number of projects steadily increased from 2012 to 2020. Finally, we analyzed 2604 AI projects at CTSA hubs using the National Institutes of Health Research Portfolio Online Reporting Tools (RePORTER) database for 2011–2019. We mapped available abstracts to medical subject headings and found that nervous system (16.3%) and mental disorders (16.2) were the most common topics addressed. From a computational perspective, big data (32.3%) and deep learning (30.0%) were most common. This work represents a snapshot in time of the role of AI in the CTSA program.
Long‐term efficacy and safety of apremilast in the treatment of plaques psoriasis: A real‐world, single‐center experience
Authors: Radi Giulia , Campanati Anna , Diotallevi Federico , Rizzetto Giulio , Martina Emanuela , Bobyr Ivan , Giannoni Melania , Offidani Annamaria
Published: October 2021

Apremilast is a small molecule approved for the treatment of plaques psoriasis and adult psoriatic arthritis. Pivotal studies have demonstrated short and long term efficacy and safety of apremilast but few data in real life are still available. The aim of this study is to report the efficacy and safety results of apremilast in clinical practice in patients with moderate‐to‐severe plaque psoriasis, focusing on therapeutic results obtained after 24 and 52 weeks of treatment. From May 2018 to December 2018, 40 patients with plaques psoriasis have been enrolled. Psoriasis Area Severity Index (PASI), body surface area, Physician Global Assessment, and Dermatology Life Quality Index (DLQI) were performed at baseline at 24 (W24) and 52 (W52) weeks after treatment initiation. Primary endpoint was to evaluate the percentage of patient that achieved PASI 75, PASI 90 and PASI 100 at week 24 and 52 of treatment. Additional measure of efficacy was percentage of patients reaching the minimal disease activity (MDA = PGA0/1 and DLQI 0/1) after 24 and 52 weeks of treatment. As secondary endpoint, we evaluated the percentage of patient that achieved DLQI 0–1 at W24 and W52, and long‐term safety of apremilast. The percentage of patients who achieved PASI75, PASI90 and PASI100 was 47.5%, 30% and 10% and 25%, 35% and 10% at W24 and W52 respectively. About the half of the reported patients reached MDA at W24 (n = 21) and at W52 (n = 20). The 60% of patients achieved and maintained DLQI 0–1 at W24 until W52. Diarrhea, nausea, headache, insomnia, and other AEs have been reported by 28 patients. Apremilast in real life experience confirmed the levels of efficacy and safety obtained in pivotal trials. In particular, the good initial response to the treatment is predictive of the maintenance or improvement of the outcome over W52. The efficacy is supported by an excellent safety profile even in frail patients.
Temporary overpessimism: Job loss expectations following a large negative employment shock
Authors: Emmler Julian , Fitzenberger Bernd
Published: October 2021

Job loss expectations were widespread amongst workers in East Germany following reunification with West Germany. Though experiencing a large negative employment shock, East German workers were nevertheless overpessimistic immediately after reunification with respect to their job loss risk. Over time, job loss expectations fell and converged to West German levels, which was driven by a stabilizing economic environment and by an adaptation of the interpretation of economic signals with workers learning to distinguish individual risk from firm‐level risk. In fact, conditional on actual job loss risk, East German workers quickly caught up to West Germans regarding the share of correctly predicted job losses.
A scoping review of the current evidence on treatment and outcomes following synovial sepsis
Authors: de Souza Therese C. , Suthers Joanna M. , Busschers Evita , Burford John H. , Freeman Sarah L.
Published: October 2021

Background

Synovial sepsis is a frequent cause of morbidity and mortality in horses. Despite advances in diagnostics and treatments, persistent infection or chronic lameness can occur.

Objectives

To perform a scoping review to identify and evaluate the current evidence on the factors implicated in the success of treatment for synovial sepsis.

Study design

Joanna Briggs Institute scoping review.

Methods

A protocol was registered, and a systematic literature search was performed on CAB abstracts, Medline, Scopus and Embase. Inclusion and exclusion criteria were developed and studies systematically reviewed against this. Studies relating to factors affecting treatment success following synovial sepsis were retained and data was extracted on study method, population characteristics and factors significantly associated with treatment outcome.

Results

In total, 2338 studies were identified, and 61 were included to full paper analysis. Eight papers reported significant factors, identifying 15 risk factors associated with two measurements of outcome, either survival and/or return to athletic function. The 15 factors were identified and categorised into pre‐, intra‐ and post‐operative factors. Risk factors that were identified included the number or type of synovial structures involved, the presence of pannus, tendon and bone pathology, and the use of systemic antimicrobials. There were many discrepancies in inclusion criteria of cases of synovial sepsis as well as measurement and description of outcome variables.

Main limitations

Non–English language studies or conference proceedings were not included. Only small numbers of papers had similar findings.

Conclusions

Standardisation of inclusion criteria is essential to enable comparisons and analysis between studies on synovial sepsis. Future studies should use methodologies to reduce bias including multicentre and multinational studies, prospective study design and robust statistical modelling.
Effects of dietary tributyrin and physterol ester supplementation on growth performance, intestinal morphology, microbiota and metabolites in weaned piglets
Authors: Chen Gang , Zhuo Ruiwen , Ding Hao , Yang Kaili , Xue Junjing , Zhang Sha , Chen Lixiang , Yin Yulong , Fang Rejun
Published: October 2021

Aim

This study was conducted to investigate the effects of dietary tributyrin (TB) and physterol ester (PSE) supplementation on the growth performance and intestinal health of weaned piglets.

Methods and Results

Ninety-six piglets were randomly allocated to one of four groups, including a control group (basal diet), TB group (basal diet + 1500 g t−1 TB), PSE group (basal diet + 300 g t−1 PSE) and TB + PSE group (basal diet + 1500 g t−1 TB + 300 g t−1 PSE). All groups had eight replicates with three piglets per replicate. The experiment lasted for 28 days. The results showed that dietary TB supplementation increased (p < 0.05) average daily feed intake and average daily gain, as well as the acetate and butyrate concentration in ileum, and dietary PSE supplementation decreased (p < 0.05) the ratio of feed to gain (F/G) on days 1–14 of the trial. Dietary TB or PSE alone supplementation improved the ratio of villus height to crypt depth (VH/CD) and the expression level of Occludin in ileum. The linear discriminant analysis effect size analysis identified eight biomarkers in the control group, 18 in the TB + PSE group, two in the PSE group in ileum respectively. Correlation analysis showed that the relative abundances of Enterococcus, and Streptococcus were positively correlated (p < 0.05) with propionate concentration, while the relative abundance of Clostridium_sensu_stricto_1 was negatively correlated (p < 0.05) with acetate concentration in ileum.

Conclusion

These findings suggest that dietary TB or PSE alone supplementation could alter the growth performance, intestinal morphology, microbiota community and metabolites of weaned piglets.

Significance and Impact of the Study

Weaning stress is a major cause of slow growth and increased diarrhoea in piglets. This study demonstrated that dietary TB and PSE presented a beneficial role in growth performance and gut health via regulating intestinal morphology, microbiota composition and metabolites.
Simultaneous evolution of host resistance and tolerance to parasitism
Authors: Singh Prerna , Best Alex
Published: October 2021

Tolerance and resistance are two modes of defence mechanisms used by hosts when faced with parasites. Here, we assume tolerance reduces infection‐induced mortality rate and resistance reduces the susceptibility of getting infected. Importantly, a negative association between these two strategies has often been found experimentally. We study the simultaneous evolution of resistance and tolerance in a host population where they are related by such a trade‐off. Using evolutionary invasion theory, we examine the patterns of optimal investment in each defence strategy, under different ecological scenarios. Our focus is on predicting which of the two strategies is favoured under various epidemiological and ecological conditions. Our key findings surround the impact of recovery and sterility of infected hosts. As the rate at which infected hosts recover from the infection, that is the recovery rate increases, the investment in tolerance increases (resistance decreases) when infected hosts are sterile, but this pattern reverses when infected hosts can reproduce. We further found that a change in the parameter determining the intraspecies competition for resources leading to a reduction in birth rate, that is the crowding factor affects investments in tolerance and resistance only when infected hosts can reproduce. These results emphasize the role of fecundity in driving the evolutionary dynamics of a host. We also find that disease prevalence can increase or decrease depending on whether or not the host evolves: prevalence is highest at low recovery rates when the host does not evolve, but the feedback of a change in tolerance and resistance reverses this pattern, leading to lower prevalence at low recovery rates as host evolves.
Quantal analysis estimates docking site occupancy determining short‐term depression at hippocampal glutamatergic synapses
Authors: Tanaka Mamoru , Sakaba Takeshi , Miki Takafumi
Published: October 2021

Before fusion, synaptic vesicles (SVs) pause at discrete release/docking sites. During repetitive stimulation, the probability of site occupancy changes following SV fusion and replenishment. The occupancy probability is considered to be one of the crucial determinants of synaptic strength, but it is difficult to estimate separately because it usually blends with other synaptic parameters. Thus, the contribution of site occupancy to synaptic function, particularly to synaptic depression, remains elusive. Here, we directly estimated the occupancy probability at the hippocampal mossy fibre‐CA3 interneuron synapse showing synaptic depression, using statistics of counts of vesicular events detected by deconvolution. We found that this synapse had a particularly high occupancy (∼0.85) with a high release probability of a docked SV (∼0.8) under 3 mm external calcium conditions. Analyses of quantal amplitudes and SV counts indicated that quantal size reduction decreased the amplitudes of all responses in a train to a similar degree, whereas release/docking site number was unchanged during trains, suggesting that quantal size and release/docking site number had little influence on the extent of synaptic depression. Model simulations revealed that the initial occupancy with high release probability and slow replenishment determined the time course of synaptic depression. Consistently, decreasing external calcium concentration reduced both the occupancy and release probability, and the reductions in turn produced less depression. Based on these results, we suggest that the occupancy probability is a crucial determinant of short‐term synaptic depression at glutamatergic synapses in the hippocampus.

image

Key points

The occupancy probability of a release/docking site by a synaptic vesicle at presynaptic terminals is considered to be one of the crucial determinants of synaptic strength, but it is difficult to estimate separately from other synaptic parameters.

Here, we directly estimate the occupancy probability at the hippocampal mossy fibre‐interneuron synapse using statistics of vesicular events detected by deconvolution.

We show that the synapses have particularly high occupancy (0.85) with high release probability (0.8) under high external calcium concentration ([Ca2+]o) conditions, and that both parameter values change with [Ca2+]o, shaping synaptic depression.

Analyses of the quantal amplitudes and synaptic vesicle counts suggest that quantal sizes and release/docking site number have little influence on the extent of synaptic depression.

The results suggest that the occupancy probability is a crucial determinant of short‐term synaptic depression at glutamatergic synapses in the hippocampus.
Extreme atomic-scale surface roughening: Amino acids on Ag on Au(111)
Authors: Boyd Kennedy P. S. , Cook Emily A. , Paszkowiak Maria A. , Iski Erin V.
Published: October 2021

A clear description of how surface morphology is affected by the bonding of biomolecules with metal surfaces is critical to identify due to the potential applications in microelectronics, medical devices, and biosensors. Amino acids (AAs) on bare Au(111) were previously observed to trap Au adatoms, eventually leading to the formation of one atom high metal islands. To better understand the role of surface identity, L-isoleucine on Au(111) modified with a Ag thin film was investigated at ambient conditions with electrochemical scanning tunneling microscopy. The mere presence of an Ag monolayer drastically changed the amino acid/surface interactions despite the chemical similarity of Au and Ag. The adsorption of the AAs on the Ag monolayer drastically altered the surface and caused significant surface roughening distinct from 2D growth which had previously existed only on top of the surface. This roughening occurred layer-by-layer and was not restricted to the first layer of the surface as seen with sulfur containing molecules. Notably, this study demonstrates surface roughening that is occurring under extremely mild conditions highlighting the ability of Ag thin films to markedly alter surface chemistry in concert with biomolecules.
The Two Dimensions of Passion for Sport: A New Look Using a Quadripartite Approach
Authors: Schellenberg Benjamin J.I. , Verner-Filion Jérémie , Gaudreau Patrick , Mbabaali Sophia
Published: October 2021

Research relying on the dualistic model of passion has consistently found that harmonious passion for sport is positively associated with adaptive outcomes and that obsessive passion for sport is positively associated with maladaptive outcomes. In this research, we tested if various sport outcomes were related to within-person combinations of both harmonious and obsessive passion. Three samples of athletes (total N = 1,290) completed online surveys that assessed various sport outcomes (e.g., sport enjoyment, goal attainment), along with harmonious and obsessive passion for their sport. We found that athletes were best served by having either high harmonious passion or low obsessive passion or, in many cases, high harmonious passion that was combined with low obsessive passion. These results add to our understanding of passion by showing that combinations of harmonious and obsessive passion for sport are differentially associated with indicators of a positive sport experience.
Theta oscillations coordinate grid-like representations between ventromedial prefrontal and entorhinal cortex
Authors: Chen Dong , Kunz Lukas , Lv Pengcheng , Zhang Hui , Zhou Wenjing , Liang Shuli , Axmacher Nikolai , Wang Liang
Published: October 2021

Human iEEG reveals synchronous theta oscillations and coordinated grid-like representations between vmPFC and entorhinal cortex.
Discovery of a Novel Glucuronan Lyase System in
Trichoderma parareesei
Authors: Pilgaard Bo , Vuillemin Marlene , Munk Line , Holck Jesper , Meier Sebastian , Wilkens Casper , Meyer Anne S.
Published: October 2021

This paper reports the discovery of a set of six complementary glucuronan lyase enzymes in the mycoparasite
Trichoderma parareseei
. Apart from the novelty of the discovery of these enzymes in
T. parareesei
, the key importance of the study is the finding that the majority of these lyases are induced when
T. parareesei
is inoculated on Basidiomycete cell walls that contain glucuronan.
Characterization of M116.1p, a Murine Cytomegalovirus Protein Required for Efficient Infection of Mononuclear Phagocytes
Authors: Ružić Tina , Juranić Lisnić Vanda , Mahmutefendić Lučin Hana , Lenac Roviš Tihana , Železnjak Jelena , Cokarić Brdovčak Maja , Vrbanović Ana , Oreb Deni , Kveštak Daria , Gotovac Jerčić Kristina , Borovečki Fran , Lučin Pero , Adler Barbara , Jonjić Stipan , Lisnić Berislav
Published: October 2021

Human cytomegalovirus (HCMV) is a species-specific herpesvirus that causes severe disease in immunocompromised individuals and immunologically immature neonates. Murine cytomegalovirus (MCMV) is biologically similar to HCMV, and it serves as a widely used model for studying the infection, pathogenesis, and immune responses to HCMV.
Deciphering the Role of Mucosal Immune Responses and the Cervicovaginal Microbiome in Resistance to HIV Infection in HIV-Exposed Seronegative (HESN) Women
Authors: Munusamy Ponnan Sivasankaran , Thiruvengadam Kannan , Tellapragada Chaitanya , Ambikan Anoop T. , Narayanan Aswathy , Kathirvel Sujitha , Mathayan Manikannan , Shankar Janani , Rajaraman Akshaya , Afshan Amanulla Mehar , Dinesha Thongadi Ramesh , Poongulali Selvamuthu , Saravanan Shanmugam , Murugavel Kailapuri Gangatharan , Swaminathan Soumya , Velu Vijayakumar , Shacklett Barbara , Neogi Ujjwal , Hanna Luke Elizabeth
Published: October 2021

The vast majority of human immunodeficiency virus (HIV) infections across the world are transmitted sexually, so understanding the correlates of protection at the genital mucosa level is very important. The genital tract mucosa is a primary site of HIV replication, and discerning the nature of HIV-specific immune responses in this compartment is crucial.
Multidrug Resistance Dynamics in Salmonella in Food Animals in the United States: An Analysis of Genomes from Public Databases
Authors: Pires João , Huisman Jana S. , Bonhoeffer Sebastian , Van Boeckel Thomas P.
Published: October 2021

Next-generation sequencing has led to an exponential increase in the number of genomes deposited in public repositories. This growing volume of information presents opportunities to track the prevalence of genes conferring antimicrobial resistance (AMR), a growing threat to the health of humans and animals.
Evaluation of RNA
later
as a Field-Compatible Preservation Method for Metaproteomic Analyses of Bacterium-Animal Symbioses
Authors: Jensen Marlene , Wippler Juliane , Kleiner Manuel
Published: October 2021

Metaproteomics, the large-scale identification and quantification of proteins from microbial communities, provide direct insights into the phenotypes of microorganisms on the molecular level. To ensure the integrity of the metaproteomic data, samples need to be preserved immediately after sampling to avoid changes in protein abundance patterns.
Synthesis and Some Properties of New 5-Hydroxy-2-[(hetarylthio)methyl]-4H-pyran-4-ones
Authors: Dotsenko V. V. , Guz D. D. , Tebiev D. T. , Kindop V. K. , Aksenov N. A. , Aksenova I. V. , Netreba E. E.
Published: October 2021

The reaction of 2-thioxoazines with chlorokojic acid in the presence of KOH in DMF led to the formation of new hybrid molecules containing fragments of kojic acid and azaheterocycle linked by the SCH2 spacer. In silico prediction of bioavailability parameters was carried out, possible protein targets were predicted by the protein ligand docking method.
Zinner’s syndrome, a retrospective series of three cases: different strategies to the same problem
Authors: Pina-Vaz Teresa , Dias Nuno , Martins Silva Carlos , Alturas Silva João
Published: October 2021

A 106 years have passed since Zinner’s syndrome was first described and current knowledge is still almost exclusively based on case reports. This article presents three patients with Zinner’s syndrome with different clinical presentations and consequent different treatment options, showing the possible full spectrum of this condition. The first patient presented with storage lower urinary tract symptoms and benefited from laparoscopic removal of the seminal vesicle. The second patient has an incidental diagnosis on CT and remains asymptomatic on follow-up. The third patient presented with persistent lumbar pain and underwent open surgical removal of the seminal vesicle. The authors further present a literature review of the current knowledge on this topic, hopefully to clarify the state of art and improve the management of these patients.
Late diagnosis of pulmonary agenesis
Authors: Pimenta Diana Alexandra , Aguiar Filipa Lemos , Fernandes Beatriz Celeiros , Rolo Rui
Published: October 2021

Pulmonary agenesis is defined as the complete absence of one or both lungs, including the bronchi, bronchioles, vasculature and lung parenchyma. Most of these malformations are detected in early childhood. A residual number remains asymptomatic and undiagnosed until adulthood. The clinical presentation is wide, ranging from asymptomatic to respiratory complaints like dyspnoea, respiratory distress and a history of recurrent lung infections. This case presents a 54-year-old woman with complaints of coughing, dyspnoea for medium exertion and wheezing for a couple of months. Based on the results of complementary diagnosis methods, right pulmonary agenesis was diagnosed without other malformations. Simultaneously, an asthma diagnosis was also performed. The treatment of pulmonary agenesis is symptomatic. Simultaneous cardiovascular malformations could require surgical interventions. This case demonstrates that pulmonary agenesis may remain undiagnosed, be identified incidentally, and have a good and long prognosis.
Distal transradial artery access for coronary angiography in a patient having rheumatoid arthritis-related severe arthropathies
Authors: Rahman Nasir , Ullah Ihsan , Farhad Awais , Adnan Ghufran
Published: October 2021

Conventional radial access has become the default access for coronary angiography. Sometime, it is difficult to take a conventional radial access, especially in patients having severe arthropathies leading to limited wrist joint mobility. In such scenarios, distal transradial access (dTRA) can be adopted. We describe a case of an elderly male patient having rheumatoid arthritis with arthropathies. He presented to us with unstable angina; coronary angiogram was advised for ischaemia assessment. Right dTRA was adopted due to severe joint deformity at wrist joint, limiting joint extension. A successful coronary angiogram was performed via the right dTRA without major discomfort and complications. Haemostasis was secured with TR band radial artery compression device. In this case report, we have evaluated the importance of practising dTRA in a patient with severe arthropathies.
Vascular endothelial growth factor tyrosine kinase inhibitor targeted therapy: a potential cause of an acute aortic dissection lesser known to the emergency physician
Authors: Ting Jocelyn , Lo Zhiwen Joseph
Published: October 2021

A 59-year-old Chinese male presented to the emergency department with acute onset epigastric pain. He had no cardiovascular risk factors and was only on targeted therapy, pazopanib, for newly diagnosed metastatic renal clear cell carcinoma. He was found to have a Stanford type B acute aortic dissection with moderately elevated systolic blood pressure of 150 mm Hg. Although not a listed side effect, various case reports have shown a potential association between the use of vascular endothelial growth factor tyrosine kinase inhibitor targeted therapy and an acute aortic dissection. It would be prudent to consider the possibility of an aortic dissection in patients on such drugs with suspicious clinical presentation, even in the absence of other risk factors.
Cerebral venous sinus thrombosis after ChAdOx1 vaccination: the first case of definite thrombosis with thrombocytopenia syndrome from India
Authors: Maramattom Boby Varkey , Moidu Fathima Mihta , Varikkottil Sajira , Syed Akheel A
Published: October 2021

Cerebral venous sinus thrombosis (CVST) following novel coronavirus-2019 (nCoV-19) vaccination is a rare adverse effect. We report the first case of CVST associated with ChAdOx1 vaccination, with positive anti-platelet factor 4 (PF4) antibodies, from India. A 44-year-old woman developed a thunderclap headache 4 days after the first dose of the adenoviral vector vaccine ChAdOx1 (Covishield). Physical examination was unremarkable barring mild neck stiffness with no focal neurological deficits. MRI identified right transverse sinus thrombosis. Laboratory tests revealed raised D-dimer and thrombocytopenia; anti-PF4 antibodies were subsequently identified, consistent with thrombosis with thrombocytopenia syndrome (TTS). She was treated with non-heparin anticoagulation and intravenous immunoglobulin and made an uneventful recovery. Early recognition of adenoviral vector vaccine-related TTS, which resembles heparin-induced thrombocytopenia syndrome, is important as heparin and heparin analogues are best avoided in the treatment.
Difficulty removing a leadless pacemaker in a post-transfusion patient
Authors: Tajima Atomu , Mizutani Yoshiaki , Kanasiro Masaaki , Amano Tetsuya
Published: October 2021

A 99-year-old woman with atrial fibrillation bradycardia and symptomatic long pauses underwent a leadless pacemaker implantation after red blood cell transfusion due to anaemia. The patient’s blood tests after transfusion showed hypercoagulability; haematocrit, haemoglobin and fibrinogen levels were increased from 24.5% to 33.2%, 76 g/L to 111g/L, and 346 mg/dL to 646 mg/dL, respectively. Blood tests showed no hereditary hypercoagulability disorder and she had no history of thrombophilia. A leadless pacemaker was implanted in the correct position in the right ventricle. Heparin was administered after sheath insertion and the leadless pacemaker system was thoroughly flushed with heparinised saline before the tether was cut; however, removing the tether after leadless pacemaker implantation was difficult because clots had formed on the tether.
Prevalence and prognostic value ofMYD88andCD79Bmutations in ocular adnexal large B-cell lymphoma: a reclassification of ocular adnexal large B-cell lymphoma
Authors: Kirkegaard Marina Knudsen , Minderman Marthe , Sjö Lene Dissing , Pals Steven T , Eriksen Patrick R G , Heegaard Steffen
Published: October 2021

Aims

To (1) reclassify ocular adnexal large B-cell lymphomas (OA-LBCLs) per 2016 WHO lymphoma classification and (2) determine the prevalence ofMYD88andCD79Bmutations and their association with clinical parameters among OA-LBCLs.

Methods

This study is a retrospective analysis of all OA-LBCLs diagnosed in Denmark between 1980 and 2018. Medical records and tissue samples were retrieved. Thirty-four OA-LBCLs were included. Fluorescence in situ hybridisation and Epstein-Barr-encoded RNA in situ hybridisation were used for the reclassification. Mutational status was established by allele-specific PCR and confirmed by Sanger sequencing. Primary endpoints were overall survival, disease-specific survival (DSS) and progression-free survival (PFS).

Results

Two LBCL subtypes were identified: diffuse large B-cell lymphoma (DLBCL) (27 of 32; 84%) and high-grade B-cell lymphoma (HGBL) withMYCandBCL2and/orBCL6rearrangements (5 of 32; 16%). cMYC/BCL2 double-expressor DLBCLs had a poorer DSS than non-double-expressor DLBCLs (5-year DSS, 25% vs 78%) (HR 0.23; 95% CI 0.06 to 0.85; p=0.014).MYD88mutations were present in 10 (29%) of 34 lymphomas and carried a poorer PFS than wild-type cases (5-year PFS, 0% vs 43%) (HR 0.78; 95% CI 0.61 to 0.98; p=0.039).CD79Bmutations were present in 3 (9%) of 34 cases.

Conclusion

OA-LBCL consists mainly of two subtypes: DLBCL and HGBL withMYCandBCL2and/orBCL6rearrangements.MYD88mutations are important drivers of OA-LBCL.MYD88mutations, as well as cMYC/BCL2 double-expressor DLBCL, appear to be associated with a poor prognosis. ImplementingMYD88mutational analysis in routine diagnostics may improve OA-LBCL prognostication.
Where there is no local author: a network bibliometric analysis of authorship parasitism among research conducted in sub-Saharan Africa
Authors: Rees Chris A , Ali Mohsin , Kisenge Rodrick , Ideh Readon C , Sirna Stephanie J , Britto Carl D , Kazembe Peter N , Niescierenko Michelle , Duggan Christopher P , Manji Karim P
Published: October 2021

Introduction

Authorship parasitism (ie, no authors affiliated with the country in which the study took place) occurs frequently in research conducted in low-income and middle-income countries, despite published recommendations defining authorship criteria. The objective was to compare characteristics of articles exhibiting authorship parasitism in sub-Saharan Africa to articles with author representation from sub-Saharan African countries.

Methods

A bibliometric review of articles indexed in PubMed published from January 2014 through December 2018 reporting research conducted in sub-Saharan Africa was performed. Author affiliations were assigned to countries based on regular expression algorithms. Choropleth maps and network diagrams were created to determine where authorship parasitism occurred, and multivariable logistic regression was used to determine associated factors.

Results

Of 32 061 articles, 14.8% (n=4754) demonstrated authorship parasitism, which was most common among studies from Somalia (n=175/233, 75.1%) and Sao Tome and Principe (n=20/28, 71.4%). Authors affiliated with USA and UK institutions were most commonly involved in articles exhibiting authorship parasitism. Authorship parasitism was more common in articles: published in North American journals (adjusted OR (aOR) 1.26, 95% CI 1.07 to 1.50) than in sub-Saharan African journals, reporting work from multiple sub-Saharan African countries (aOR 8.41, 95% CI 7.30 to 9.68) compared with work from upper-middle income sub-Saharan African countries, with <5 authors (aOR 14.46, 95% CI 12.81 to 16.35) than >10 authors, and was less common in articles published in French (aOR 0.60, 95% CI 0.41 to 0.85) than English.

Conclusions

Authorship parasitism was common in articles reporting research conducted in sub-Saharan Africa. There were reliable predictors of authorship parasitism. Investigators and institutions in high-income countries, as well as funding agencies and journals should promote research from sub-Saharan Africa, including its publication, in a collaborative and equitable manner.
Autoimmune glial fibrillary acidic protein astrocytopathy presented as ataxia, myoclonus and bulbar syndrome: a case report and review of the literature
Authors: C Novo Azael , Venegas Pérez Begoña
Published: October 2021

Objective

To describe an atypical case of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.

Results

A patient in his 60s presented with 6 months of progressive ataxia, proximal myoclonus and bulbar symptomatology. Cerebrospinal fluid (CSF) analysis showed monocytic pleocytosis, elevated protein level and elevated adenosine deaminase (ADA) level. CSF microbiological studies were negative and brain and cervical MRI showed no significant findings. We tested for nuclear, cytoplasmatic and synaptic neural autoantibodies as well as anti-GFAP antibodies. While awaiting these results, the patient was commenced on methylprednisolone boluses (1 g/day for 5 days), noting rapid neurological improvement. Eventually, CSF tests were positive for anti-GFAP antibodies.

Conclusion

We report atypical manifestations of GFAP astrocytopathy. Further research is needed to fully understand the spectrum of neurological manifestations of this autoimmune disease and facilitate timely diagnosis.
Antineoplastic prescription among patients with colorectal cancer in eight major cities of China, 2015–2019: an observational retrospective database analysis
Authors: Yao Difei , Yu Lingyan , He Wei , Hu Yangmin , Xu Huimin , Yuan Ying , Dai Haibin
Published: October 2021

Objectives

It is unclear what is driving rising colorectal cancer (CRC) treatment costs in China, whether an adjustment in drug prices changes use and total cost. This study aims to estimate trends in drug use, prescribing patterns and spending for antineoplastic drug therapies for CRC in major cities of China.

Methods

Information from 128 811 antineoplastic drug prescriptions in CRC was retrospectively collected from the Hospital Prescription Analysis Cooperative Project. The prescriptions extracted included demographic information of patients, the generic name and the price of antineoplastic drugs. The Mann-Kendall and Cochran-Armitage trend test was used to estimate the trends of antineoplastic agent usage.

Results

The number of antineoplastic prescriptions ranged from 18 966 in 2015 to 34 219 in 2019. Among the prescriptions collected in this study, the annual cost of antineoplastic drugs increased by 117.2%, and average prescription cost increased by 20%. Throughout the study period, the most prescribed antineoplastic drugs were capecitabine, oxaliplatin, fluorouracil and irinotecan, representing 49%, 27%, 21% and 9% of (per cent of visits (PV)). The PV of bevacizumab and cetuximab increased by 494% and 338% (from 1.8% and 1.3% in 2015 to 10.7% and 5.7% in 2019). In prescribing patterns of antineoplastic agents, monotherapy gradually decreased, while combination therapy, especially three-drug combination, increased significantly from 1.35% to 7.31%.

Conclusion

This study estimated recent trends of antineoplastic drug use and expenditure for Chinese patients with CRC. These results would inform CRC treatment decisions, including health insurance negotiation, precision therapy access, allocation of research funding and evaluation of the financial burden of CRC drug treatment.
Response to cardiac resynchronisation therapy in men and women: a secondary analysis of the SMART-AV randomised controlled trial
Authors: Howell Stacey , Stivland Timothy M , Stein Kenneth , Ellenbogen Kenneth , Tereshchenko Larisa G
Published: October 2021

Objectives

There is a controversy about whether both sexes’ response to cardiac resynchronisation therapy (CRT) is similar. We aimed to assess a causal effect of sex on CRT response.

Design

Secondary analysis of a randomised controlled trial (RCT) data. Doubly robust augmented-inverse-probability-weighted (AIPW) estimation of sex effect on CRT response.

Setting

The SmartDelay Determined Atrioventricular (AV) Optimisation (SMART-AV) RCT.

Participants

The SMART-AV RCT enrolled New York Heart Association class III-IV patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤35% despite optimal medical therapy and QRS duration ≥120 ms, in sinus rhythm. After exclusion of those with missing outcome or covariates, 741 participants (age 66±11 years; 33% female; 78% white; LVEF 28%±9%; 58% ischaemic cardiomyopathy; 75% left bundle branch block; left ventricular end-systolic volume index (LVESVI) 65±30 mL/m2) were included.

Interventions

Implanted CRT defibrillator with randomly assigned AV delay as either (1) fixed at 120 ms, or (2) echocardiography-determined, or (3) SmartDelay algorithm-programmed.

Outcome

A composite of freedom from death and HF hospitalisation and a >15% reduction in LVESVI at 6 month post-CRT was the endpoint.

Results

The primary endpoint was met by 337 patients (45.5%); 134 were women (55.6% response) and 203 were men (40.6% response); p<0.0001. After conditioning for 33 covariates that included baseline demographic, clinical, ECG, echocardiographic and biomarker characteristics, known predictors of CRT response, logistic regression showed a higher probability for composite CRT response for women versus men (OR 1.79; 95% CI 1.08 to 2.98; p<0.0001), whereas AIPW estimation showed no difference in CRT response (average treatment effect 0.88; 95% CI 0.41 to 1.89; p=0.739). After removing colliders from the model, both logistic regression (OR 1.00; 95% CI 0.69 to 1.44) and AIPW (ATE 1.06; 95% CI 0.96 to 1.16) reported similar results.

Conclusions

Both sexes’ response to CRT is similar. Sex differences in HF substrate, treatment and comorbidities explain sex disparities in CRT outcomes.

Trial registration number

ClinicalTrials.gov Identifier;NCT00677014.
Decision (not) to disclose mental health conditions or substance abuse in the work environment: a multiperspective focus group study within the military
Authors: Bogaers Rebecca , Geuze Elbert , van Weeghel Jaap , Leijten Fenna , Rüsch Nicolas , van de Mheen Dike , Varis Piia , Rozema Andrea , Brouwers Evelien
Published: October 2021

Objectives

Many workers in high-risk occupations, such as soldiers, are exposed to stressors at work, increasing their risk of developing mental health conditions and substance abuse (MHC/SA). Disclosure can lead to both positive (eg, support) and negative (eg, discrimination) work outcomes, and therefore, both disclosure and non-disclosure can affect health, well-being and sustainable employment, making it a complex dilemma. The objective is to study barriers to and facilitators for disclosure in the military from multiple perspectives.

Design

Qualitative focus groups with soldiers with and without MHC/SA and military mental health professionals. Sessions were audiotaped and transcribed verbatim. Content analysis was done using a general inductive approach.

Setting

The study took place within the Dutch military.

Participants

In total, 46 people participated in 8 homogeneous focus groups, including 3 perspectives: soldiers with MHC/SA (N=20), soldiers without MHC/SA (N=10) and military mental health professionals (N=16).

Results

Five barriers for disclosure were identified (fear of career consequences, fear of social rejection, lack of leadership support, lack of skills to talk about MHC/SA, masculine workplace culture) and three facilitators (anticipated positive consequences of disclosure, leadership support, work-related MHC/SA). Views of the stakeholder groups were highly congruent.

Conclusions

Almost all barriers (and facilitators) were related to fear for stigma and discrimination. This was acknowledged by all three perspectives, suggesting that stigma and discrimination are considerable barriers to sustainable employment and well-being. Supervisor knowledge, attitudes and behaviour were critical for disclosure, and supervisors thus have a key role in improving health, well-being and sustainable employment for soldiers with MHC/SA. Furthermore, adjustments could be made by the military on a policy level, to take away some of the fears that soldiers have when disclosing MHC/SA.
Challenges and solutions: surveying researchers on what type of community engagement and involvement activities are feasible in low and middle income countries during the COVID-19 pandemic
Authors: Kroese Karolin , Porter Katie , Surridge Heidi , Tembo Doreen
Published: October 2021

Objectives

Measures to limit the spread of infection during the COVID-19 global pandemic have made engaging and involving members of the community in global health research more challenging. This research aimed to explore how global health researchers adapted to the imposed pandemic measures in low and middle income countries (LMICs) and how they overcame challenges to effective community engagement and involvement (CEI).

Design

A qualitative two-stage mixed-methods study involving an online survey and a virtual round table.

Setting

The survey and round table were completed online.

Participants

Of 53 participants, 43 were LMIC-based or UK-based global health researchers and/or CEI professionals, and 10 worked for the National Institute for Health Research or UK Government’s Department of Health and Social Care.

Outcome measures

This study aimed to capture data on: the number of CEI activities halted and adapted because of the COVID-19 pandemic; where CEI is possible; how it has been adapted; what the challenges and successes were; and the potential impact of adapted or halted CEI on global health research.

Results

Pandemic control measures forced the majority of researchers to stop or amend their planned CEI activities. Most face-to-face CEI activities were replaced with remote methods, such as online communication. Virtual engagement enabled researchers to maintain already established relationships with community members, but was less effective when developing new relationships or addressing challenges around the inclusion of marginalised community groups.

Conclusions

COVID-19 has highlighted the need for contingency planning and flexibility in CEI. The redesigning and adopting of remote methods has come with both advantages and disadvantages, and required new skills, access to technology, funding, reliable services and enthusiasm from stakeholders. The methods suggested have the potential to augment or substitute previously preferred CEI activities. The effectiveness and impact of these remote CEI activities need to be assessed.
Barriers and determinants of asthma control in children and adolescents in Africa: a systematic review
Authors: Mphahlele Reratilwe Ephenia , Kitchin Omolemo , Masekela R
Published: October 2021

Objective

To identify reasons for poor asthma control in African children and adolescents.

Design

Systematic review

Data sources

PubMed, Scopus, CINHAL, PsycINFO, MEDLINE and Web of Science databases were systematically searched up to 31 May 2020. Hand searching was done on Sabinet, African Journal online and Google Scholar.

Eligibility criteria

Studies identifying barriers to asthma control, where asthma control was assessed by the validated Asthma Control Test/Child Asthma Control Test and/or Asthma Control Questionnaire were included.

Data extraction and synthesis

Two reviewers independently selected studies for inclusion with disagreements resolved by a research team discussion, including a third reviewer. Data were extracted using the Cochrane Effective Practice and Organization of Care data collection form. The quality of the included studies was assessed using the modified Newcastle-Ottawa quality assessment scale. Identified barriers were reported in a thematic narrative synthesis.

Primary outcomes

Poorly controlled asthma and associated factors.

Results

From 914 records, three studies conducted between 2014 and 2019 in Nigeria, Uganda and South Africa met the inclusion criteria. A total of 883 children aged 4–19 years were analysed. Older age, concurrent allergy and city-dwelling significantly impacted asthma control. Few children with asthma symptoms in the community had ever used inhaled corticosteroids (6.7%) and identified reasons included lack of asthma diagnosis (38.8%) and no prescribed treatment (47.6%).

Conclusion

Asthma control in African children is impacted by age, allergy, urbanisation and lack of access to asthma diagnosis and treatment. More studies focusing on identifying barriers to asthma control in Africa are needed.

PROSPERO

Registration no: CRD42020196755)
Dehydroepiandrosterone (DHEA) role in enhancement and maintenance of implantation (DREAM): randomised double-blind placebo-controlled trial—study protocol
Authors: Noushin Majiyd Abdul , Sahu Apeksha , Singh Swati , Singh Sankalp , Jayaprakasan Kannamannadiar , Basheer Reema , Ramachandran Aravind , Ashraf Mohamed
Published: October 2021

Introduction

Dehydroepiandrosterone (DHEA) is an important precursor of androgen and has been studied and researched extensively for improving the various outcome measures of ovarian stimulation in women with advanced age or poor ovarian response. Androgens also play an important role in the enhancement of endometrial and decidual function by regulating both the transcriptome and secretome of the endometrial stromal cells and have a positive effect on various factors like insulin-like growth factor binding protein 1, homeobox genes (HOXA10, HOXA11), secreted phosphoprotein 1, prolactin which are necessary for implantation. It is well-known that the circulating ‘precursor pool’ of DHEA declines with age more so in poor ovarian reserve patients and exogenous supplementation may be beneficial in such cases. This double-blinded randomised controlled trial (RCT) aims to test the hypothesis whether transient targeted supplementation of DHEA as an adjuvant to progesterone in frozen embryo transfer (FET) cycles, for women with low serum testosterone, helps in improving live birth rate.

Methods and analysis

This study is planned as a double-blinded, placebo-controlled randomised trial and the sample size, calculated for the primary outcome measure—live birth rate, is 140. All participants will be having a flexible antagonist protocol for controlled ovarian stimulation and an elective freeze-all policy for the embryos as per the hospital protocol after written informed consent. For FET, the endometrium will be prepared by hormone replacement treatment protocol. During the FET cycle, the intervention group will be receiving DHEA 25 mg two times a day for 15 days from the day of starting progesterone supplementation and the control group will be receiving a placebo.

Ethics and dissemination

The approval of the study was granted by the Clinical Trials Registry—India and the Institutional Ethical Committee of CRAFT Hospital and Research Center. All participants will provide written informed consent before being randomised into allocated treatment groups. The results will be disseminated to doctors and patients through conference presentations, peer-reviewed publications, social media and patient information booklets.

Trial registration numbers

CTRI/2020/06/025918; ECR/1044/Inst/KL/2018.