bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-sensitivity cardiac troponin I: is ethnicity relevant?
Authors: Kalaria Tejas R , Harris Nicola , Sensi Harminder , Valentine Ross , Asif Usama , Sharrod-Cole Hayley , Coley-Grant Deon , Min San San , Ford Clare , Gama Rousseau 
Published: March 2021

AimsTo evaluate 99th percentile upper reference limits (URLs) and investigate ethnic differences for the Abbott Architect high-sensitivity cardiac troponin I (hs-cTnI) in a middle-aged to elderly cosmopolitan population.MethodsIn subjects without cardiovascular disease and after outlier exclusion, data on hs-cTnI from 149 white men, 150 white women, 150 South Asian (SA) men and 150 SA women in their sixth, seventh and eight decades were analysed. Each ethnicity–gender–decade subgroup consisted of 50 patients except white men in their sixth decade (n=49).ResultsThe overall, women and men hs-cTnI 99th percentile URLs were 22.1, 17.9 and 24.8 ng/L, respectively. Median (IQR) hs-cTnI was higher in men (2.7 (1.8–4.1) ng/L) than in women (1.9 (1.1–3.2) ng/L; p<0.001). White men (3.2 (2.2–4.4) ng/L) had higher hs-cTnI than SA men (2.5 (1.6–3.6) ng/L; p<0.001), white women (2.1 (1.3–3.3) ng/L; p<0.001) and SA women (1.6 (1.0–3.0) ng/L; p<0.001). Hs-cTnI in white women was similar to SA women (p=0.07) and SA men (p=0.07). Patients in the eighth decade had higher hs-cTnI (p<0.05) than those in sixth decade within each ethnicity–gender subgroup. Of significant associations, age had the greatest impact on hs-cTnI followed by gender and then ethnicity.ConclusionWe report white–SA differences in hs-cTnI in men and a similar trend in women. We confirm age and gender differences in hs-cTnI, irrespective of ethnicity. Further studies are required to determine whether ethnicity-specific age and gender 99th percentile URLs improve detection or exclusion of myocardial injury.
Validation of multiplex immunofluorescence and digital image analysis for programmed death-ligand 1 expression and immune cell assessment in non-small cell lung cancer: comparison with conventional immunohistochemistry
Authors: Wu Jianghua , Mao Luning , Sun Wei , Yang Xin , Wang Haiyue , Liu Xinying , Chi Kaiwen , Huang Xiaozheng , Lin Dongmei 
Published: March 2021

AimsThis study aimed to validate the application of combined multiplex immunofluorescence (mIF) and digital image analysis (DIA) in formalin-fixed and paraffin-embedded tissues for the quantitative assessment of programmed death-ligand 1(PD-L1) and immune cells (ICs) in non-small cell lung cancer (NSCLC).MethodsFifty resected samples of NSCLC were sequentially stained with a DNA-tagged mIF (panel including PD-L1, CKpan, CD8, CD68 and 4′,6-diamidino-2-phenylindole (DAPI)) and conventional immunohistochemistry (cIHC). The assessment of cell density and consistency of tumour proportion score (TPS) via DIA were compared with those by pathologists.ResultsA strong correlation in the cell population of immune markers was obtained between mIF and cIHC (for PD-L1: R=0.9304, CKpan: R=0.8231, CD8: R=0.9314 and CD68: R=0.8366) within 95% limits of agreement. The continuous TPS calculated using mIF was highly consistent with the IHC staining results which were evaluated by pathologists (R=0.9362). However, in the comparison of TPS using interval variables, a poor agreement was obtained at a cut-off of 1% (κ=0.197), whereas excellent agreement was achieved at cut-offs of 50% (κ=0.908) and 5% (κ=0.823). DIA on mIF showed that PD-L1 commonly colocalised with CD68+macrophages and CD8+cytotoxic cells were closer to PD-L1-/CK+tumour cells (TCs) than to PD-L1+/CK+TCs in spatial distribution.ConclusionsA combination of mIF and DIA is useful for the quantification of PD-L1 expression and IC populations in NSCLC. Further validation of TPS at a cut-off of 1% and assay harmonisation is essential for translating this method in a diagnostic setting.
Suicide attempt and intentional self-harm during the earlier phase of the COVID-19 pandemic in Washtenaw County, Michigan
Authors: Bergmans Rachel S , Larson Peter S 
Published: March 2021

ObjectiveDetermine the early impact of the COVID-19 pandemic on emergency department (ED) encounters for suicide attempt and intentional self-harm at a regional tertiary academic medical centre in Washtenaw County, Michigan, which is one of the wealthier and more diverse counties in the state.MethodsInterrupted time series analysis of daily ED encounters from October 2015 through October 2020 for suicide attempt and intentional self-harm (subject n=3002; 62% female; 78% Caucasian) using an autoregressive integrated moving average modelling approach.ResultsThere were 39.9% (95% CI 22.9% to 53.1%) fewer ED encounters for suicide attempt and intentional self-harm during the first 7 months of the COVID-19 pandemic (ie, on or after 10 March 2020, when the first cases of COVID-19 were identified in Michigan).ConclusionsFewer individuals sought emergency care for suicide-related behaviour during the earlier phase of the COVID-19 pandemic than expected when compared to prior years. This suggests initial outbreaks of COVID-19 and state of emergency executive orders did not increase suicide-related behaviour in the short term. More work is needed to determine long-term impacts of the COVID-19 pandemic on suicide-related behaviour and whether there are high-risk groups.
Activation of cryptic donor splice sites by non-coding and codingPAX6variants contributes to congenital aniridia
Authors: Tarilonte Maria , Ramos Patricia , Moya Jennifer , Fernandez-Sanz Guilermo , Blanco-Kelly Fiona , Swafiri Saoud Tahsin , Villaverde Cristina , Romero Raquel , Tamayo Alejandra , Gener Blanca , Calvas Patrick , Ayuso Carmen , Corton Marta 
Published: March 2021

BackgroundThe paired-domain transcription factor paired box gene 6 (PAX6) causes a wide spectrum of ocular developmental anomalies, including congenital aniridia, Peters anomaly and microphthalmia. Here, we aimed to functionally assess the involvement of seven potentially non-canonical splicing variants on missplicing of exon 6, which represents the main hotspot region for loss-of-functionPAX6variants.MethodsBy locus-specific analysis ofPAX6using Sanger and/or targeted next-generation sequencing, we screened a Spanish cohort of 106 patients withPAX6-related diseases. Functional splicing assays were performed by in vitro minigene approaches or directly in RNA from patient-derived lymphocytes cell line, when available.ResultsFive out seven variants, including three synonymous changes, one small exonic deletion and one non-canonical splice variant, showed anomalous splicing patterns yielding partial exon skipping and/or elongation.ConclusionWe describe new spliceogenic mechanisms forPAX6variants mediated by creating or strengthening five different cryptic donor sites at exon 6. Our work revealed that the activation of crypticPAX6splicing sites seems to be a recurrent and underestimated cause of aniridia. Our findings pointed out the importance of functional assessment of apparently silentPAX6variants to uncover hidden genetic alterations and to improve variant interpretation for genetic counselling in aniridia.
Timing of primary syphilis treatment and impact on the development of treponemal antibodies: a cross-sectional clinic-based study
Authors: Towns Janet M , Leslie David E , Denham Ian , Azzato Francesca , Karapanagiotidis Theo , Williamson Deborah A , Graves Stephen R , Fairley Christopher K , Bissessor Melanie , Chow Eric P F , Zhang Lei , Chen Marcus Y 
Published: March 2021

BackgroundSerology is negative in a proportion of primary syphilis cases where Treponema pallidum PCR testing is positive. We aimed to identify discordant, T. pallidum PCR-positive, serology-negative primary syphilis cases and any clinical or laboratory factors associated with failure to subsequently seroconvert.MethodsSerodiscordant primary syphilis cases that were T. pallidum PCR-positive and serology-negative (including rapid plasma reagin, T. pallidum particle agglutination, T. pallidum enzyme immunoassay or T. pallidum chemiluminescence assay) were identified from the Melbourne Sexual Health Centre electronic records between April 2011 and December 2019. Clinical and laboratory associations were examined.ResultsThere were 814 primary syphilis cases in the study period and 38 (4.7%) were serodiscordant, 35 in men who have sex with men. Thirty-two had follow-up serology performed a median of 24 days later, of which 16 (50%) seroconverted, mostly (81%) within 6 weeks. Failure to seroconvert was significantly associated with treatment on day 1. Of the 12 cases treated on day 1, 10 (83%) failed to seroconvert compared with 6 of 20 (30%) among those who were treated after day 1.DiscussionEarlier treatment of primary syphilis can prevent the development of serological markers. T. pallidum PCR can identify primary syphilis lesions before the development of serological markers and improve diagnosis of early primary syphilis lesions. Serology alone will miss a proportion of primary syphilis infections and should be repeated if a diagnosis of syphilis is being considered.
Neurotoxicities in the treatment of HIV between dolutegravir, rilpivirine and dolutegravir/rilpivirine: a meta-analysis
Authors: Allen Reeves Anthony , Fuentes Andrea V , Caballero Joshua , Thomas Jennifer E , Mosley II Juan F , Harrington Catherine 
Published: March 2021

ObjectiveTo assess the risk of neuropsychiatric adverse effects (ie, depression, anxiety, insomnia, dizziness, suicidal behaviour) among patients treated with rilpivirine, dolutegravir and dolutegravir/rilpivirine.DesignThis is a systematic review and meta-analysis of randomised controlled trials. Quality of evidence was assessed using Jadad scoring system.Data sourcesThree electronic databases were searched for available publications up to 1 May 2020. Searches included relevant studies, trial registers, conference proceeding abstracts and grey literature.Inclusion criteriaRandomised controlled trials with data focused on adult participants (ie, 18 years of age or older) receiving dolutegravir 50 mg, rilpivirine 25 mg or combination of dolutegravir 50 mg/rilpivirine 25 mg once daily.ResultsTwenty studies with a minimum duration of 48 weeks and average Jadad score of 4 were included (n=10 998). Primary objective demonstrated a relative risk (RR) synergistic effect on depressive symptoms for dolutegravir/rilpivirine (RR=2.82; 95% CI (1.12 to 7.10)) when compared with dolutegravir (RR=1.10; 95% CI (0.88 to 1.38)) and rilpivirine (RR=1.08; 95% CI (0.80 to 1.48)). Secondary objectives showed no difference between dolutegravir, rilpivirine and dolutegravir/rilpivirine to efavirenz. Additionally, excluding efavirenz studies, dolutegravir and dolutegravir/rilpivirine yielded increased depression (RR=1.34; 95% CI (1.04 to 1.74)).ConclusionThe combination of dolutegravir/rilpivirine appears to increase the risk of depressive symptoms. Despite the increase, the clinical significance is unknown and needs further study. Additionally, neurotoxicity risk appears similar between dolutegravir, rilpivirine and dolutegravir/rilpivirine antiretroviral therapy when compared with efavirenz-based antiretroviral therapy.
Clinical efficacy and tolerability of 1.5 g/day oral amoxicillin therapy without probenecid for the treatment of syphilis
Authors: Ikeuchi Kazuhiko , Fukushima Kazuaki , Tanaka Masaru , Yajima Keishiro , Imamura Akifumi 
Published: March 2021

ObjectivesIntramuscular benzathine penicillin G is not available in certain countries. In a previous report, 3 g/day amoxicillin with probenecid was shown to be effective in treating syphilis in patients with HIV; however, 7.3% of patients changed their therapy owing to adverse events. The objective of this study was to assess the clinical efficacy and tolerability of 1.5 g/day amoxicillin without probenecid for the treatment of syphilis.MethodsThe routine clinical records of patients diagnosed with syphilis and treated with 1.5 g/day amoxicillin at a tertiary care hospital between 2006 and 2018 were retrospectively analysed. Syphilis was diagnosed if serum rapid plasma reagin (RPR) titres were ≥8 RU and the Treponema pallidum latex-agglutination test was positive. Serological cure was defined as a ≥fourfold decrease in the RPR titre within 12 months in symptomatic early syphilis and within 24 months in latent syphilis.ResultsOverall, 138 patients (112 with HIV) were analysed. The percentages of primary, secondary, early latent, late latent and latent syphilis of unknown duration were 8.0%, 50.0%, 25.4%, 5.8% and 10.9%, respectively. The median treatment duration was 4.5 weeks (IQR 4–8 weeks), which was not related to the stage of syphilis. Two patients (1.5%) changed treatment due to skin rash. The rate of serological cure was 94.9% (131/138; 95% CI 89.8% to 97.9%) overall; 93.8% (105/112; 95% CI 87.5% to 97.5%) in patients with HIV and 100% (26/26; 95% CI 86.8% to 100%) in patients without HIV. Treatment duration was not related to the treatment efficacy.ConclusionThe regimen of 1.5 g/day amoxicillin without probenecid is highly effective with a low switch rate in patients with and without HIV.
Evidence of HIV pre-exposure or post-exposure prophylaxis (PrEP/PEP) among blood donors: a pilot study, England June 2018 to July 2019
Authors: Harvala Heli , Reynolds Claire , Ijaz Samreen , Maddox Vicki , Penchala Sujan Dilly , Amara Alieu , Else Laura , Brailsford Susan , Khoo Saye 
Published: March 2021

ObjectiveDue to increased use of pre-exposure prohylaxis (PrEP) and its potential to affect HIV screening of blood donors, we undertook antiretroviral residual testing among HIV-negative male donors in England.MethodsResidual plasma samples were obtainnd from 46 male donors confirmed positive for syphilis and 96 donors who were repeat reactive for HIV antibodies in screening but confirmed as HIV-negative by reference testing. These were tested for concentrations of tenofovir and emtricitabine by high-performance liquid chromatograhpy coupled with mass spectrometry.ResultsWe found evidence of pre-exposure or post-exposure prophylaxis (PrEP/PEP) use in three male blood donors confirmed positive for syphilis (3 out of 46 screened, 6.5%). Two were estimated to have taken PrEP/PEP within a day of donating, and the third within 2 days. Two were new donors, whereas one had donated previously but acquired syphilis infection after his last donation.ConclusionsOur findings indicate that a small proportion of blood donors have not been disclosing PrEP/PEP use and therefore donating in non-compliance to donor eligibility criteria.
Impact of aspiration catheter size on first-pass effect in the combined use of contact aspiration and stent retriever technique
Authors: Pérez-García Carlos , Maegerlein Christian , Rosati Santiago , Rüther Charlotte , Gómez-Escalonilla Carlos , Zimmer Claus , Arrazola Juan , Berndt Maria Teresa , Moreu Manuel 
Published: March 2021

Background and purposeThe first-pass effect (FPE), defined as a first-pass Expanded Treatment in Cerebral Ischaemia (eTICI) 2c/3 reperfusion, has emerged as a key metric of efficacy in mechanical thrombectomy (MT) for acute ischaemic stroke. The proximal balloon occlusion together with direct thrombus aspiration during stent retriever thrombectomy (PROTECT)-PLUS technique consists in the use of a balloon guide catheter and a combined MT approach involving contact aspiration and a stent retriever. The aim of this study is to assess the effectiveness and safety of the PROTECT-PLUS technique using distal aspiration catheters (DACs) with different inner diameters by comparing the large-bore DAC Catalyst 7 versus the use of medium-bore DACs.MethodsRetrospective analysis of a prospectively maintained database of patients treated with PROTECT-PLUS using Catalyst 7, Catalyst 6 or Catalyst 5 with an occlusion of either the terminal carotid artery or the M1 or M2 segments of the middle cerebral artery from 2018 to 2020 in two comprehensive stroke centres. Baseline characteristics and procedural, safety and clinical outcomes were compared between groups. Multivariable logistic regression analysis was performed in order to find independent predictors of FPE.ResultsWe identified 238 consecutive patients treated with PROTECT-PLUS as front-line approach using Catalyst 7 (n=86), Catalyst 6 (n=78) and Catalyst 5 (n=76). The rate of FPE was higher with Catalyst 7 (54%) than Catalyst 6 (33%, p=0.009) and Catalyst 5 (32%, p=0.005), in addition to higher final eTICI 2c/3 reperfusion rates, shorter procedural times, lower need of rescue therapy and fewer procedure-related complications. After multivariable analysis the sole independent factor associated to FPE was the use of Catalyst 7 (OR 2.34; 95% CI 1.19 to 4.58; p=0.014).ConclusionFurther development of combined MT by incorporating larger-bore aspiration catheters is associated with higher reperfusion rates, shorter procedure times, and lower need of rescue therapy while reducing the complication rates.
Impact of COVID-19 lockdown on smoking consumption in a large representative sample of Italian adults
Authors: Carreras Giulia , Lugo Alessandra , Stival Chiara , Amerio Andrea , Odone Anna , Pacifici Roberta , Gallus Silvano , Gorini Giuseppe 
Published: March 2021

ObjectivesItaly is one of the first countries that imposed a nationwide stay-at-home order during the COVID-19 outbreak, inevitably resulting in changes in lifestyles and addictive behaviours. The aim of this work is to investigate the impact of lockdown restrictions on smoking habits using data collected within the Lost in Italy project.MethodsA web-based cross-sectional study was conducted on a representative sample of 6003 Italian adults aged 18–74 years. Study subjects were recruited from 27 April to 3 May 2020 and were asked to report changes in smoking habits before the lockdown and at the time of interview.ResultsDuring the lockdown, 5.5% of the overall sample quit or reduced smoking, but 9.0% of the sample started, relapsed smoking or increased their smoking intensity. In total, the lockdown increased cigarette consumption by 9.1%. An improvement in smoking habits was associated with younger age, occasional smoking and unemployment, whereas a worsening was mainly associated with mental distress. In particular, an increase in cigarette consumption during lockdown was more frequently reported among those with worsening quality of life (OR: 2.05; 95% CI: 1.49 to 2.80), reduction in sleep quantity (OR: 2.29; 95% CI: 1.71 to 3.07) and increased anxiety (OR: 1.83; 95% CI: 1.38 to 2.43) and depressive symptoms (OR: 2.04; 95% CI: 1.54 to 2.71).ConclusionsCOVID-19 lockdown had a huge impact on smoking consumption of the Italian general population. The main concern is for smokers who increase their cigarette consumption due to an increased mental distress. Providing greater resources for cessation services capable of reducing mental health symptoms in smokers is urgently needed.
Prognostic Role of Prior Heart Failure Hospitalization Among Patients Hospitalized for Worsening Chronic Heart Failure
Authors: Blumer Vanessa , Mentz Robert J. , Sun Jie-Lena , Butler Javed , Metra Marco , Voors Adriaan A. , Hernandez Adrian F. , O’Connor Christopher M. , Greene Stephen J. 
Published: March 2021

Background:
Hospitalization for heart failure (HF) is associated with increased risk of death among patients with chronic HF. The degree to which hospitalization for HF is a distinct biologic entity with independent prognostic value versus a marker of higher risk chronic HF patients is unclear.

Methods:
After excluding patients with new-onset HF, the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) included 4205 patients hospitalized for worsening chronic HF with reduced or preserved ejection fraction. The present analysis compared patients by presence or absence of prior HF hospitalization within 12 months and by timing of prior HF hospitalization relative to index hospitalization. Associations with 180-day all-cause mortality were assessed, including adjustment for 27 prespecified clinical factors.

Results:

Overall, 2241 (53.3%) patients had a HF hospitalization within the prior 12 months and 1964 (46.7%) did not. Mortality rates at 180 days were 15.5% and 11.9%, respectively. In unadjusted analyses, prior HF hospitalization was associated with increased risk of 180-day mortality (HR, 1.35 [95% CI, 1.14–1.59];
P
<0.01). After adjustment, the point estimate was attenuated and the association not statistically significant (HR, 1.18 [95% CI, 0.99–1.40];
P
=0.064). Similarly, after adjustment, compared with patients without prior hospitalization, prior HF hospitalization was not associated with mortality, irrespective of timing (0–4 months: HR, 1.10 [95% CI, 0.87–1.39],
P
=0.41; 4–8 months: HR, 0.95 [95% CI, 0.70–1.27];
P
=0.72; 8–12 months: HR, 1.06 [95% CI, 0.74–1.51],
P
=0.77; >12 months: HR, 0.81 [95% CI, 0.63–1.06],
P
=0.12).

Conclusions:
In this cohort of patients hospitalized for worsening HF, prior HF hospitalization was not associated with 180-day mortality after comprehensively accounting for patient characteristics measured during the index patient visit. Clinical confounders measured at the point-of-care may explain previously observed associations between prior HF hospitalization and mortality, and these clinical factors may be a more direct means of predicting patient survival.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT00475852.
CausaLM: Causal Model Explanation Through Counterfactual Language Models
Authors: Feder Amir , Oved Nadav , Shalit Uri , Reichart Roi 
Published: March 2021

Abstract
Understanding predictions made by deep neural networks is notoriously difficult, but also crucial to their dissemination. As all machine learning–based methods, they are as good as their training data, and can also capture unwanted biases. While there are tools that can help understand whether such biases exist, they do not distinguish between correlation and causation, and might be ill-suited for text-based models and for reasoning about high level language concepts. A key problem of estimating the causal effect of a concept of interest on a given model is that this estimation requires the generation of counterfactual examples, which is challenging with existing generation technology. To bridge that gap, we propose CausaLM, a framework for producing causal model explanations using counterfactual language representation models. Our approach is based on fine-tuning of deep contextualized embedding models with auxiliary adversarial tasks derived from the causal graph of the problem. Concretely, we show that by carefully choosing auxiliary adversarial pre-training tasks, language representation models such as BERT can effectively learn a counterfactual representation for a given concept of interest, and be used to estimate its true causal effect on model performance. A byproduct of our method is a language representation model that is unaffected by the tested concept, which can be useful in mitigating unwanted bias ingrained in the data.
Technology and Ecosocialism
Authors: Wallis Victor 
Published: March 2021

Abstract
Ecosocialist technology is technology guided by universal human need and by concern for the health of the natural environment. It contrasts with capitalist technology, which is driven above all by the imperatives of cost-reduction and profit-maximization within a market whose contours are shaped by the owners or state agents of capital. The contrast between ecosocialist and capitalist technology appears across all sectors of production and services. Following a theoretical overview, we examine the sectors of transport, housing, and food production and reflect on the newest technologies of communication, surveillance, and artificial intelligence. I argue that devices and infrastructures that would transform the conditions of life should in all cases be subject, at the planning stage, to full disclosure, informed public debate, and democratic resolution.