bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol: effect of infection, Modic and inflammation on clinical outcomes in surgery for radiculopathy (EIMICOR)
Authors: Djuric Niek , Lafeber Geraldine , van Duinen Sjoerd G. , Bernards Sandra , Peul Wilco C. , Vleggeert-Lankamp Carmen L. A. 
Published: September 2021

Abstract
Background
Evidence indicates that inflammatory processes are involved in radicular pain as well as in resorption of herniated disc tissue. Furthermore there are indications that the presence of vertebral end plate pathology (Modic changes; MC) is associated with a negative effect on inflammation. It is hypothesized that in patients with MC, the (possibly bacterial induced) inflammation will be accompanied by pro inflammatory cytokines that worsen the outcome, and that in patients without MC, the inflammation is accompanied by cytokines that induce a resorption process to accelerate recovery.

Methods
This prospective cohort study will include 160 lumbar and 160 cervical patients (total of 320), which are scheduled for surgery for either a lumbar or cervical herniated disc with ages between 18 and 75. The main and interaction effects of local bacterial infection (culture), inflammatory cells in disc material (immunohistology), MC (MRI), and blood biomarkers indicating inflammation or infection (blood sample evaluation) will be evaluated. Clinical parameters to be evaluated are leg pain on the 11 point NRS pain scale, Oswestry (lumbar spine) or Neck (cervical spine) Disability Index, Global Perceived Recovery, Womac Questionnaire, and medication status, at baseline, and after 6, 16, 26 and 52 weeks.

Discussion
Gaining insight in the aetiology of pain and discomfort in radiculopathy caused by a herniated disc could lead to more effective management of patients. If the type of inflammatory cells shows to be of major influence on the rate of recovery, new immunomodulating treatment strategies can be developed to decrease the duration and intensity of symptoms. Moreover, identifying a beneficial inflammatory response in the disc through a biomarker in blood could lead to early identification of patients whose herniations will resorb spontaneously versus those that require surgery.

Trial registration
prospectively enrolled at trialregister.nl, ID:NL8464.
Combined effects of cigarette smoking, DNA methyltransferase 3B genetic polymorphism, and DNA damage on lung cancer
Authors: Huang Chia-Chen , Lai Chung-Yu , Tsai Chin-Hung , Wang Jiun-Yao , Wong Ruey-Hong 
Published: September 2021

Abstract
Background
Smoking increases DNA methylation and DNA damage, and DNA damage acts as a vital cause of tumor development. The DNA methyltransferase 3B (DNMT3B) enhances promoter activity and methylation of tumor suppressor genes. Tea polyphenols may inhibit DNMT activity. We designed a case-control study to evaluate the combined effects of smoking, green tea consumption, DNMT3B − 149 polymorphism, and DNA damage on lung cancer occurrence.

Methods
Questionnaires were administered to obtain demographic characteristics, life styles, and family histories of lung cancer from 190 primary lung cancer cases and 380 healthy controls. Genotypes and cellular DNA damage were determined by polymerase chain reaction and comet assay, respectively.

Results
The mean DNA tail moment for lung cancer cases was significantly higher than that for healthy controls. Compared to nonsmokers carrying the DNMT3B − 149 CT genotype, smokers carrying the TT genotype had a greater lung cancer risk (odds ratio [OR]: 2.83, 95% confidence interval [CI]: 1.62–4.93). DNA damage levels were divided by the tertile of the healthy controls’ values. Compared to nonsmokers with low DNA damage, smokers with moderate DNA damage (OR: 2.37, 95% CI: 1.54–3.63) and smokers with high DNA damage (OR: 3.97, 95% CI: 2.63–5.98) had elevated lung cancer risks. Interaction between smoking and DNA damage significantly affected lung cancer risk.

Conclusions
Our study suggested that the DNMT3B − 149 TT genotype, which has higher promoter activity, can increase the lung cancer risk elicited by smoking, and DNA damage may further promote smoking related lung cancer development.
Identifying pain trajectories in children and youth with cerebral palsy: a pilot study
Authors: Shearer Heather M. , Côté Pierre , Hogg-Johnson Sheilah , McKeever Patricia , Fehlings Darcy L. 
Published: September 2021

Abstract
Background
Although chronic pain is common in children with cerebral palsy (CP), little is known about short-term pain fluctuations and their impact on children’s well-being. High-quality cohort studies are needed to understand the clinical course of pain in this population. We aimed to determine the feasibility of conducting a multicentre cohort study. In this pilot study we assessed: 1) study processes, 2) resource and 3) management indicators including recruitment and follow-up rates, data completeness, participant characteristics, and successes and barriers in the study conduct.

Methods
A multi-centre pilot cohort study was conducted with 10 Canadian children/youth with CP attending one of two children’s rehabilitation centers. We collected self-reported pain intensity (Faces Pain Scale-Revised [FPS-R], Numeric Rating Scale [NRS]); pain interference (PROMIS PI); pain location (pain diagram); physical and psychological well-being (KIDSCREEN-27), sleep characteristics, preceding months’ interventions, and some clinical characteristics at baseline. Average pain intensity was reported weekly for five weeks. Well-being, sleep and interventions were measured at baseline and again at five weeks. We used feasibility indicators to evaluate:1) study processes (e.g. recruitment, attrition rates); 2) resources (e.g. data completion, budgetary challenges); and 3) management (e.g. data optimization, variability of participants and pain scores).

Results
Between March and May 2019, 24 children and their parents/guardians were contacted and 20 met eligibility criteria. Of those, 10 agreed to in-person screening (50%) and were subsequently enrolled. The follow-up rate was 90% and self-reported missing data was minimal. Ninety percent of participants chose e-questionnaire follow-ups versus mailed paper questionnaires. Sixty percent required reminders to complete e-follow-ups. Participants were aged 8-17 years, five were female, GMFCS levels I-IV (none with level V), 90% had spastic CP and 80% reported having pain in the preceding week. Pain intensity (FPS-R) between participants ranged from 0-8/10 at baseline and 0-6/10 across all four weekly follow-ups.

Conclusions
This pilot study demonstrates the feasibility of conducting a multicentre cohort study to identify short-term pain trajectories and measure their association with well-being in children and youth with CP. Additional strategies to improve recruitment and accessibility for those with GMFCS levels V should be implemented in future studies.
Symptoms of post-traumatic stress disorder (PTSD) in next of kin during suspension of ICU visits during the COVID-19 pandemic: a prospective observational study
Authors: Zante Bjoern , Erne Katja , Grossenbacher Julia , Camenisch Sabine A. , Schefold Joerg C. , Jeitziner Marie-Madlen 
Published: September 2021

Abstract
Background
During the COVID-19 pandemic, suspension of visits by next of kin to patients in intensive care units (ICU), to prevent spread of the SARS-CoV-2 virus, has been a common practice. This could impede established family-centered care and may affect the mental health of the next of kin. The aim of this study was to explore symptoms of post-traumatic stress syndrome (PTSD) in the next of kin of ICU patients.

Methods
In this prospective observational single-center study, next of kin of ICU patients were interviewed by telephone, using the Impact of Event Scale-Revised (IES-R), to assess symptoms of acute stress disorder during the ICU stay and PTSD symptoms at 3 months after the ICU stay. The primary outcome was the prevalence of severe PTSD symptoms (IES-R score ≥ 33) at 3 months. The secondary outcomes comprised the IES-R scores during the ICU stay, at 3 months, and the prevalence of severe symptoms of acute stress disorder during ICU stay. An inductive content analysis was performed of the next of kin’s comments regarding satisfaction with patient care and the information they were given.

Results
Of the 411 ICU patients admitted during the study period, 62 patients were included together with their next of kin. An IES-R score > 33 was observed in 90.3% (56/62) of next of kin during the ICU stay and in 69.4% (43/62) 3 months later. The median IES-R score was 49 (IQR 40–61) during the ICU stay and 41 (IQR 30–55) at 3 months. The inductive content analysis showed that communication/information (55%), support (40%), distressing emotions (32%), and suspension of ICU visits (24%) were mentioned as relevant aspects by the next of kin.

Conclusions
During the suspension of ICU visits in the COVID-19 pandemic, high prevalence and severity of both symptoms of acute stress disorder during the ICU stay and PTSD symptoms 3 months later were observed in the next of kin of ICU patients.
Social and structural factors associated with depression and suicidality among men who have sex with men and transgender women in Nepal
Authors: Storm Sanna , Deuba Keshab , Shrestha Rachana , Pandey Lok Raj , Dahal Deepak , Shrestha Madan Kumar , Pokhrel Tara Nath , Marrone Gaetano 
Published: September 2021

Abstract
Introduction
The prevalence of depression and suicidality is high among men who have sex with men (MSM) and transgender women (TGW) worldwide. Stigma and discrimination are likely contributing factors. More research is needed in low-income, non-English speaking countries to assess the effects of social and structural factors on depression and suicidality among MSM and TGW.

Methods
Nepalese MSM and TGW (n = 340) were recruited using a respondent-driven sampling design and filled out a survey questionnaire. The outcomes were depression and suicidality. Data was analyzed using bivariate and multivariable logistic regression.

Results
More than half of the participants (59%) suffered from depression. Severe depression was more common among TGW compared to MSM (41 and 20%, respectively). When it comes to suicidality, TGW had higher lifetime prevalence of suicidal thoughts compared to MSM (32 and 5%, respectively). Depression was positively associated with sex work both for MSM (AOR: 7.9; 95% CI 3.4–18.2) and TGW (AOR: 6.5; 95% CI: 2.3–18.2). MSM who were evicted by family had high odds of suicidal thoughts (AOR: 6.2; 95% CI: 1.3–28.8). For TGW, suicidality was associated with being cheated and threatened (AOR: 3.9; 95% CI: 1.2–12.5) and having forced to marry a female (AOR: 2.2; 95% CI 1.1–5.1).

Conclusions
Nepalese MSM and TGW suffer from a high degree of mental and psychosocial health issues. Future studies should focus on intervention research and on collecting data from a larger variety of gender and sexual minorities.
Bacteriostatic effects of benzyl isothiocyanate on Vibrio parahaemolyticus: Transcriptomic analysis and morphological verification
Authors: Liu Jianan , Zhang Ke , Song Jie , Wu Hongyan , Hao Hongshun , Bi Jingran , Hou Hongman , Zhang Gongliang 
Published: September 2021

Abstract
Background
Foodborne illness caused by Vibrio parahaemolyticus (V. parahaemolyticus) is generally associated with the consumption of seafood. Fish and other seafood can be contaminated with V. parahaemolyticus, natural inhabitants of the marine, estuarine, and freshwater environment. In this study, the antibacterial activities of benzyl isothiocyanate (BITC) against V. parahaemolyticus were investigated by both transcriptomic analysis and morphological verification.

Results
Treatment with 1/8 minimum inhibitory concentration (1/8 MIC) BITC resulted in 234 upregulated genes and 273 downregulated genes. The results validated by quantitative real-time polymerase chain reaction (qRT-PCR) revealed that the relative expression levels of the six genes VP0820, VP0548, VP2233, VPA2362, fliA and fliG were only 31.0%, 31.1%, 55.8%, 57.0%, 75.3%, and 79.9% of the control group, respectively. Among them, genes VP2233, fliA and fliG are related to flagella and VP2362 can regulate a protein relevant to biofilm formation. Morphologically, we verified that the swimming diffusion diameter of V. parahaemolyticus was significantly reduced by 14.9% by bacterial swimming ability, and biofilm formation was significantly inhibited by treatment with 1/8 MIC BITC by crystal violet quantification assay.

Conclusions
These results indicated that 1/8 MIC BITC had antibacterial effect on V. parahaemolyticus by inhibiting virulence gene expression related to flagella and biofilm.
Defining ethical challenge(s) in healthcare research: a rapid review
Authors: Schofield Guy , Dittborn Mariana , Selman Lucy Ellen , Huxtable Richard 
Published: September 2021

AbstractBackgroundDespite its ubiquity in academic research, the phrase ‘ethical challenge(s)’ appears to lack an agreed definition. A lack of a definition risks introducing confusion or avoidable bias. Conceptual clarity is a key component of research, both theoretical and empirical. Using a rapid review methodology, we sought to review definitions of ‘ethical challenge(s)’ and closely related terms as used in current healthcare research literature.MethodsRapid review to identify peer-reviewed reports examining ‘ethical challenge(s)’ in any context, extracting data on definitions of ‘ethical challenge(s)’ in use, and synonymous use of closely related terms in the general manuscript text. Data were analysed using content analysis. Four databases (MEDLINE, Philosopher’s Index, EMBASE, CINAHL) were searched from April 2016 to April 2021.Results393 records were screened, with 72 studies eligible and included: 53 empirical studies, 17 structured reviews and 2 review protocols. 12/72 (17%) contained an explicit definition of ‘ethical challenge(s), two of which were shared, resulting in 11 unique definitions. Within these 11 definitions, four approaches were identified: definition through concepts; reference to moral conflict, moral uncertainty or difficult choices; definition by participants; and challenges linked to emotional or moral distress. Each definition contained one or more of these approaches, but none contained all four. 68/72 (94%) included studies used terms closely related to synonymously refer to ‘ethical challenge(s)’ within their manuscript text, with 32 different terms identified and between one and eight different terms mentioned per study.ConclusionsOnly 12/72 studies contained an explicit definition of ‘ethical challenge(s)’, with significant variety in scope and complexity. This variation risks confusion and biasing data analysis and results, reducing confidence in research findings. Further work on establishing acceptable definitional content is needed to inform future bioethics research.
ONTbarcoder and MinION barcodes aid biodiversity discovery and identification by everyone, for everyone
Authors: Srivathsan Amrita , Lee Leshon , Katoh Kazutaka , Hartop Emily , Kutty Sujatha Narayanan , Wong Johnathan , Yeo Darren , Meier Rudolf 
Published: September 2021

AbstractBackgroundDNA barcodes are a useful tool for discovering, understanding, and monitoring biodiversity which are critical tasks at a time of rapid biodiversity loss. However, widespread adoption of barcodes requires cost-effective and simple barcoding methods. We here present a workflow that satisfies these conditions. It was developed via “innovation through subtraction” and thus requires minimal lab equipment, can be learned within days, reduces the barcode sequencing cost to < 10 cents, and allows fast turnaround from specimen to sequence by using the portable MinION sequencer.ResultsWe describe how tagged amplicons can be obtained and sequenced with the real-time MinION sequencer in many settings (field stations, biodiversity labs, citizen science labs, schools). We also provide amplicon coverage recommendations that are based on several runs of the latest generation of MinION flow cells (“R10.3”) which suggest that each run can generate barcodes for > 10,000 specimens. Next, we present a novel software, ONTbarcoder, which overcomes the bioinformatics challenges posed by MinION reads. The software is compatible with Windows 10, Macintosh, and Linux, has a graphical user interface (GUI), and can generate thousands of barcodes on a standard laptop within hours based on only two input files (FASTQ, demultiplexing file). We document that MinION barcodes are virtually identical to Sanger and Illumina barcodes for the same specimens (> 99.99%) and provide evidence that MinION flow cells and reads have improved rapidly since 2018.ConclusionsWe propose that barcoding with MinION is the way forward for government agencies, universities, museums, and schools because it combines low consumable and capital cost with scalability. Small projects can use the flow cell dongle (“Flongle”) while large projects can rely on MinION flow cells that can be stopped and re-used after collecting sufficient data for a given project.
SOCRATES-CoMix: a platform for timely and open-source contact mixing data during and in between COVID-19 surges and interventions in over 20 European countries
Authors: Verelst Frederik , Hermans Lisa , Vercruysse Sarah , Gimma Amy , Coletti Pietro , Backer Jantien A. , Wong Kerry L. M. , Wambua James , van Zandvoort Kevin , Willem Lander , Bogaardt Laurens , Faes Christel , Jarvis Christopher I. , Wallinga Jacco , Edmunds W. John , Beutels Philippe , Hens Niel 
Published: September 2021

Abstract
Background
SARS-CoV-2 dynamics are driven by human behaviour. Social contact data are of utmost importance in the context of transmission models of close-contact infections.

Methods
Using online representative panels of adults reporting on their own behaviour as well as parents reporting on the behaviour of one of their children, we collect contact mixing (CoMix) behaviour in various phases of the COVID-19 pandemic in over 20 European countries.
We provide these timely, repeated observations using an online platform: SOCRATES-CoMix. In addition to providing cleaned datasets to researchers, the platform allows users to extract contact matrices that can be stratified by age, type of day, intensity of the contact and gender. These observations provide insights on the relative impact of recommended or imposed social distance measures on contacts and can inform mathematical models on epidemic spread.

Conclusion
These data provide essential information for policymakers to balance non-pharmaceutical interventions, economic activity, mental health and wellbeing, during vaccine rollout.
Performance of acute respiratory distress syndrome definitions in a high acuity paediatric intensive care unit
Authors: Rudolph Michelle , van Dijk Jefta , de Jager Pauline , Dijkstra Sandra K. , Burgerhof Johannes G. M. , Blokpoel Robert G. T. , Kneyber Martin C. J. 
Published: September 2021

Abstract
Background
For years, paediatric critical care practitioners used the adult American European Consensus Conference (AECC) and revised Berlin Definition (BD) for acute respiratory distress syndrome (ARDS) to study the epidemiology of paediatric ARDS (PARDS). In 2015, the paediatric specific definition, Paediatric Acute Lung Injury Consensus Conference (PALICC) was developed. The use of non-invasive metrics of oxygenation to stratify disease severity were introduced in this definition, although this potentially may lead to a confounding effect of disease severity since it is more common to place indwelling arterial lines in sicker patients. We tested the hypothesis that PALICC outperforms AECC/BD in our high acuity PICU, which employs a liberal use of indwelling arterial lines and high-frequency oscillatory ventilation (HFOV).

Methods
We retrospectively collected data from children < 18 years mechanically ventilated for at least 24 h in our tertiary care, university-affiliated paediatric intensive care unit. The primary endpoint was the difference in the number of PARDS cases between AECC/BD and PALICC. Secondary endpoints included mortality and ventilator free days. Performance was assessed by the area under the receiver operating characteristics curve (AUC-ROC).

Results
Data from 909 out of 2433 patients was eligible for analysis. AECC/BD identified 35 (1.4%) patients (mortality 25.7%), whereas PALICC identified 135 (5.5%) patients (mortality 14.1%). All but two patients meeting AECC/Berlin criteria were also identified by PALICC. Almost half of the cohort (45.2%) had mild, 33.3% moderate and 21.5% severe PALICC PARDS at onset. Highest mortality rates were seen in patients with AECC acute lung injury (ALI)/mild Berlin and severe PALICC PARDS. The AUC-ROC for Berlin was the highest 24 h (0.392 [0.124–0.659]) after onset. PALICC showed the highest AUC-ROC at the same moment however higher than Berlin (0.531 [0.345–0.716]). Mortality rates were significantly increased in patients with bilateral consolidations (9.3% unilateral vs 26.3% bilateral, p = 0.025).

Conclusions
PALICC identified more new cases PARDS than the AECC/Berlin definition. However, both PALICC and Berlin performed poorly in terms of mortality risk stratification. The presence of bilateral consolidations was associated with a higher mortality rate. Our findings may be considered in future modifications of the PALICC criteria.
The efficacy of insecticide-treated window screens and eaves against Anopheles mosquitoes: a scoping review
Authors: Anaele Beverly I. , Varshney Karan , Ugwu Francis S. O. , Frasso Rosemary 
Published: September 2021

Abstract
Background
Female mosquitoes serve as vectors for a host of illnesses, including malaria, spread by the Plasmodium parasite. Despite monumental strides to reduce this disease burden through tools such as bed nets, the rate of these gains is slowing. Ongoing disruptions related to the COVID-19 pandemic may also negatively impact gains. The following scoping review was conducted to examine novel means of reversing this trend by exploring the efficacy of insecticide-treated window screens or eaves to reduce Anopheles mosquito bites, mosquito house entry, and density.

Methods
Two reviewers independently searched PubMed, Scopus, and ProQuest databases on 10 July, 2020 for peer-reviewed studies using insecticide-treated screens or eaves in malaria-endemic countries. These articles were published in English between the years 2000–2020. Upon collection, the reports were stratified into categories of biting incidence and protective efficacy, mosquito entry and density, and mosquito mortality.

Results
Thirteen out of 2180 articles were included in the final review. Eaves treated with beta-cyfluthrin, transfluthrin or bendiocarb insecticides were found to produce vast drops in blood-feeding, biting or mosquito prevalence. Transfluthrin-treated eaves were reported to have greater efficacy at reducing mosquito biting: Rates dropped by 100% both indoors and outdoors under eave ribbon treatments of 0.2% transfluthrin (95% CI 0.00–0.00; p < 0.001). Additionally, co-treating window screens and eaves with polyacrylate-binding agents and with pirimiphos-methyl has been shown to retain insecticidal potency after several washes, with a mosquito mortality rate of 94% after 20 washes (95% CI 0.74–0.98; p < 0.001).

Conclusions
The results from this scoping review suggest that there is value in implementing treated eave tubes or window screens. More data are needed to study the longevity of screens and household attitudes toward these interventions.