bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Association and prediction utilizing craniocaudal and mediolateral oblique view digital mammography and long-term breast cancer risk
Authors: Chen Simin , Tamimi Rulla M. , Colditz Graham A. , Jiang Shu
Published: August 2023

Abstract
Mammographic percent volumetric density is an important risk factor for breast cancer. Epidemiology studies historically used film images often limited to craniocaudal (CC) views to estimate area-based breast density. More recent studies using digital mammography images typically utilize the averaged density between craniocaudal (CC) and mediolateral oblique (MLO) view mammography for 5- and 10-year risk prediction. The performance in using either and both mammogram views has not been well-investigated. We use 3,804 full-field digital mammograms from the Joanne Knight Breast Health Cohort (294 incident cases and 657 controls), to quantity the association between volumetric percent density extracted from either and both mammography views and to assess the 5 and 10-year breast cancer risk prediction performance. Our results show that the association between percent volumetric density from CC, MLO, and the average between the two, retain essentially the same association with breast cancer risk. The 5- and 10-year risk prediction also show similar prediction accuracy. Thus, one view is sufficient to assess association and predict future risk of breast cancer over a 5 or 10-year interval.
What Portuguese as a Foreign Language tells us about forms of address: an analysis of discourses of legitimation
Authors: Faria Rita
Published: August 2023

This study examines how didactic materials of Portuguese as a Foreign Language (textbooks, grammars) describe forms of address in European Portuguese and the discourses they postulate to legitimise verbal addressive behaviour, in particular when it comes to the pronoun você. The main findings are: textbooks and grammars legitimise the usage of você whilst excluding vós, despite the fact that some acknowledge the ambiguous status of você as neither a T nor a V form; the complexity and instability of the system of forms of address means that they are present in textbooks primarily apropos of other linguistic content (grammatical items such as verb conjugations, speech acts such as requests, introductions, greeting), usually precluding the field of Portuguese as a Foreign Language from postulating clear, transparent explanations guiding foreign learners in how to address others.
Encruzilhadas do Artigo Científico: língua, plano de texto, tempos verbais e voz autoral
Authors: Santos Joana Vieira , Silva Paulo Nunes da
Published: August 2023

O presente trabalho incide na análise de textos do género artigo científico com o objetivo de identificar e sistematizar algumas das suas principais propriedades. Foi analisado um corpus de 60 exemplares de Ciências (C) e de Ciências Sociais e Humanas / Humanidades (CSHH), focando a atenção em propriedades como a língua de divulgação usada, a voz autoral, o uso predominante de tempos verbais e o plano de texto adotado. Ao contrastar artigos de C e de CSHH, a análise das propriedades mencionadas permitiu detetar cruzamentos e influências recíprocas. De acordo com os dados obtidos, artigos de CSHH apresentam maior variedade no uso dos diversos mecanismos analisados, construindo vozes autorais e um posicionamento mais individualizado, ao passo que os artigos de C, escritos exclusivamente em inglês, refletem a opção por recursos mais uniformizados e formulaicos.
Abordagem dos gêneros de texto nas questões de língua portuguesa do Enem
Authors: Gondim Ana Angélica Lima , Silva Meire Celedonio da
Published: August 2023

Este trabalho tem como objetivo analisar o tratamento dado ao gênero de texto e suas dimensões contextuais e linguísticas nas questões das provas do ENEM na área de “Línguas, códigos e suas tecnologias”, especificamente nas de Língua Portuguesa. A partir dessa perspectiva, lançamos a seguinte questão: essas dimensões são abordadas para compreender o gênero como tal? Para isso, realizamos um levantamento quanti-qualitativo das provas regulares do Enem, abrangendo o período de 2015 a 2020. Como base teórica para essa análise, aderimos aos pressupostos do Interacionismo Sociodiscursivo, na análise predominantemente descendente de gêneros e o tratamento do texto como um sistema complexo, para o qual o texto é constituído por duas faces, uma dimensão social e uma dimensão linguística.
Las relaciones entre gramática del texto y escritura en los currículos españoles de lenguas primeras
Authors: Rodríguez-Gonzalo Carmen
Published: August 2023

La incorporación de los planteamientos discursivos en la enseñanza de lenguas primeras en los currículos españoles de Primaria y Secundaria se realiza en los años 90 del s.XX, en sintonía con lo ocurrido en muchos otros lugares. Se pretendía con ello un cambio de rumbo que centrara la enseñanza de la lengua en el desarrollo de las capacidades discursivas de los estudiantes. Se acudió entonces a las ciencias del lenguaje que se ocupaban del texto, como unidad lingüístico-comunicativa. Particularmente compleja y controvertida fue la articulación de los contenidos gramaticales al servicio de las capacidades discursivas. Tras el tiempo transcurrido, en este artículo analizamos qué contenidos de gramática del texto se han asentado en los currículos españoles de lenguas primeras (castellano, catalán, gallego, vasco, aragonés y asturiano), cuál es el planteamiento metodológico que se propugna en relación con ellos y qué relaciones se establecen con la escritura de textos.
Manipulação de factos e de opiniões. O debate presidencial entre Marcelo Rebelo de Sousa e André Ventura (2021)
Authors: Braz Ana Cristina , Marques Isabelle Simões
Published: August 2023

O presente trabalho tem como objetivo primordial realizar uma análise linguístico-discursiva das estratégias de argumentação e de persuasão predominantes no debate de 06 de janeiro de 2021 para as eleições presidenciais em Portugal, evidenciando as estratégias de manipulação dos locutores e candidatos. Debruçamo-nos sobre a natureza dos objetos de manipulação, assim como sobre as configurações que essa manipulação assume no género discursivo em questão e respetivas finalidades. Examinamos o apelo às emoções, aos valores e à mudança realizado pelos dois candidatos. São objeto de estudo as imagens (ethos) que os adversários políticos constroem de si e do outro no e pelo discurso, as emoções (pathos) que suscitam as suas palavras, os principais valores axiológicos dos lexemas e expressões utilizados, e os modos de refutação de factos e pontos de vista convocados. Este estudo insere-se na perspetiva da análise do discurso, assim como no quadro do estudo da argumentação, nomeadamente da argumentação no discurso político.
Friedrich Heinrich Jacobi e a crítica à imediatez no idealismo alemão
Authors: Ferrer Diogo
Published: August 2023

Este artigo estuda o papel de Jacobi nas transformações do pensamento de Fichte e de Hegel. (1) Começamos por evidenciar como as Cartas a Moses Mendelssohn de Jacobi e a subsequente querela do panteísmo contribuíram para trazer para o centro da discussão, no final do Séc. XVIII, a ideia de uma filosofia monista. (2) Mostramos então a importância da crítica de Jacobi a Kant para os desenvolvimentos seguintes, abordando (3) o seu impacto na evolução da Doutrina da ciência de Fichte e, (4) por fim, como o pensamento de Jacobi acerca da função da mediação no conhecimento condicionou Hegel.
O “Fragmento”: Primeira resposta de Fichte à “Carta” de Jacobi
Authors: Radrizzani Ives
Published: August 2023

Este artigo examina alguns aspectos da “querela sobre o ateísmo” entre F. H. Jacobi e Fichte. Em 1799, Jacobi redige a Carta a Fichte, na qual a doutrina da ciência é designada como niilista. Especial atenção será dada à resposta pouco conhecida e não publicada de Fichte Rükerinnerungen, Antworten, Fragen (Reminiscências, respostas, perguntas) e ao fragmento de uma carta que Fichte envia a Jacobi e Reinhold. Ali, Fichte ressalta a oposição entre sua filosofia e a de Jacobi, que equivale à oposição entre o ponto de vista da vida e da especulação. Embora ambos sejam contrários, podem coexistir com igual direito, desde que um não queira legislar sobre o outro.
PAD4-Induced NETosis Via Cathepsin G–Mediated Platelet-Neutrophil Interaction in ChAdOx1 Vaccine-Induced Thrombosis—Brief Report
Authors: Carnevale Roberto , Leopizzi Martina , Dominici Marcello , d’Amati Giulia , Bartimoccia Simona , Nocella Cristina , Cammisotto Vittoria , D’Amico Alessandra , Castellani Valentina , Baratta Francesco , Bertelli Alessia , Arrivi Alessio , Toni Danilo , De Michele Manuela , Pignatelli Pasquale , Marcucci Rossella , Violi Francesco
Published: August 2023

BACKGROUND:

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare syndrome characterized by platelet anti-PF4 (platelet-activating antiplatelet factor 4)–related thrombosis. Platelet-neutrophil interaction has been suggested to play a role, but the underlying mechanism has not been fully elucidated.

METHODS:

The study included 10 patients with VITT after ChAdOx1 (chimpanzee adenovirus Oxford 1) nCoV-19 (Oxford-AstraZeneca) vaccine administration, 10 patients with ischemic stroke (IS), 10 patients with acute deep vein thrombosis, and 10 control subjects in whom blood levels of neutrophil extracellular traps (NETs), soluble TF (tissue factor), and thrombin generation were examined. Furthermore, we performed in vitro studies comparing the effect of serum from patients and controls on NETs formation. Finally, immunohistochemistry was performed in cerebral thrombi retrieved from a patients with VITT and 3 patients with IS.

RESULTS:

Compared with patients with IS, patients with deep vein thrombosis, controls, and patients with VITT had significantly higher blood values of CitH3 (citrullinated histone H3), soluble TF, D-dimer, and prothrombin fragment 1+2 (
P
<0.0001). Blood CitH3 significantly correlated with blood soluble TF (Spearman rank correlation coefficient=0.7295;
P
=0.0206) and prothrombin fragment 1+2 (Spearman rank correlation coefficient=0.6809;
P
<0.0350) in patients with VITT. Platelet-neutrophil mixture added with VITT plasma resulted in higher NETs formation, soluble TF and thrombin generation, and platelet-dependent thrombus growth under laminar flow compared with IS and deep vein thrombosis plasma; these effects were blunted by PAD4 (protein arginine deiminase 4) and cathepsin G inhibitors, anti-FcγRIIa (Fc receptor for IgG class IIa), and high doses of heparin. Immunohistochemistry analysis showed a more marked expression of PAD4 along with more diffuse neutrophil infiltration and NETs formation as well as TF and cathepsin expression in VITT thrombus compared with thrombi from patients with IS.

CONCLUSIONS:

Patients with VITT display enhanced thrombogenesis by PAD4-mediated NETs formation via cathepsin G–mediated platelet/neutrophil interaction.
Prognosis of Right Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
Authors: Fayssoil Abdallah , Mansencal Nicolas , Nguyen Lee S. , Nardi Olivier , Yaou Rabah Ben , Leturcq France , Amthor Helge , Wahbi Karim , Becane Henri Marc , Lofaso Frederic , Prigent Helene , Bassez Guillaume , Behin Anthony , Stojkovic Tanya , Fontaine Bertrand , Duboc Denis , Dubourg Olivier , Clair Bernard , Laforet Pascal , Annane Djillali , Orlikowski David
Published: August 2023

Background

Chronic respiratory failure and heart involvement may occur in Duchenne muscular dystrophy. We aimed to assess the prognostic value of the right ventricular (RV) systolic dysfunction in patients with Duchenne muscular dystrophy.

Methods and Results

We studied 90 genetically proven patients with Duchenne muscular dystrophy from 2010 to 2019, to obtain respiratory function and Doppler echocardiographic RV systolic function. Prognostic value was assessed in terms of death and cardiac events. The median age was 27.5 years, and median forced vital capacity was at 10% of the predicted value: 83 patients (92%) were on home mechanical ventilation. An RV systolic dysfunction was found in 46 patients (51%). In patients without RV dysfunction at inclusion, a left ventricular systolic dysfunction at inclusion was associated with a higher risk of developing RV dysfunction during follow‐up with an odds ratio of 4.5 (
P
=0.03). RV systolic dysfunction was significantly associated with cardiac events, mainly acute heart failure (62%) and cardiogenic shock (23%). In a multivariable Cox model, the adjusted hazard ratio was 4.96 (95% CI [1.09–22.6];
P
=0.04). In terms of death, we found a significant difference between patients with RV dysfunction versus patients without RV dysfunction in the Kaplan–Meier curves (log‐rank
P
=0.045).

Conclusions

RV systolic dysfunction is frequently present in patients with Duchenne muscular dystrophy and is associated with increased risk of cardiac events, irrespective of left ventricular dysfunction and mechanical ventilation.

Registration

URL:
https://www.clinicaltrials.org
; unique identifier: NCT02501083.
Proteome‐Wide Mendelian Randomization Analysis Identified Potential Drug Targets for Atrial Fibrillation
Authors: Wang Xinpei , Huang Tao , Jia Jinzhu
Published: August 2023

Background

Finding effective and safe therapeutic drugs for atrial fibrillation (AF) is an important concern for clinicians. Proteome‐wide Mendelian randomization analysis provides new ideas for finding potential drug targets.

Methods and Results

Using a proteome‐wide Mendelian randomization approach, we assessed the genetic predictive causality between thousands of proteins and AF risk and found that genetically predicted plasma levels of phosphomevalonate kinase, tumor necrosis factor ligand superfamily member 12, sulfhydryl oxidase 2, interleukin‐6 receptor subunit alpha, and low‐affinity immunoglobulin gamma Fc region receptor II‐b might decrease AF risk, while genetically predicted plasma levels of beta‐mannosidase, collagen alpha‐1(XV) chain, ANXA4 (annexin A4), COF2 (cofilin‐2), and RAB1A (Ras‐related protein Rab‐1A) might increase AF risk (
P
<3.4×10
−5
). By using different Mendelian randomization methods and instrumental variable selection thresholds, we performed sensitivity analyses in 30 scenarios to test the robustness of positive findings. Replication analyses were also performed in independent samples to further avoid false‐positive findings. Drugs targeting tumor necrosis factor ligand superfamily member 12, interleukin‐6 receptor subunit alpha, low‐affinity immunoglobulin gamma Fc region receptor II‐b, and annexin A4 are approved or in development. The results of the phenome‐wide Mendelian randomization analysis showed that changing the plasma levels of phosphomevalonate kinase, cofilin‐2, annexin A4, Ras‐related protein Rab‐1A, sulfhydryl oxidase 2, and collagen alpha‐1(XV) chain did not increase the risk of other diseases while decreasing the risk of AF.

Conclusions

We found a significant causal association between genetically predicted levels of 10 plasma proteins and AF risk. Four of these proteins have drugs targeting them that are approved or in development, and our results suggest the potential for these drugs to treat AF or cause AF. Sulfhydryl oxidase 2, low‐affinity immunoglobulin gamma Fc region receptor II‐b, and beta‐mannosidase have not been suggested by previous laboratory or epidemiological studies to be associated with AF and may reveal new pathophysiological pathways as well as therapeutic targets for AF.
Utilization and Outcomes of Primary Prevention Implantable Cardioverter‐Defibrillators in Patients With Hypertrophic Cardiomyopathy
Authors: Goldstein Sarah A. , Kennedy Kevin F. , Friedman Daniel J. , Al‐Khatib Sana M. , Wang Andrew
Published: August 2023

Background

There is uncertainty about the appropriate use of primary prevention implantable cardioverter‐defibrillators (ICDs) among older patients with hypertrophic cardiomyopathy.

Methods and Results

Patients with hypertrophic cardiomyopathy who received a primary prevention ICD between 2010 and 2016 were identified using the National Cardiovascular Data Registry ICD Registry. Trends in ICD utilization and patient characteristics were assessed over time. Using linked Centers for Medicare and Medicaid Service claims data, Cox proportional hazard models assessed factors associated with mortality and postdischarge hospitalization for cardiac arrest/ventricular arrhythmia. Of 5571 patients with hypertrophic cardiomyopathy, 1511 (27.1%) were ≥65 years old. ICD utilization increased over time in all age groups. There were no changes in the prevalence of risk factors for sudden cardiac death over time. The variables most strongly associated with postdischarge mortality were older age (adjusted hazard ratio (aHR) 1.80 [95% CI, 1.47–2.21]), New York Heart Association class (III/IV versus I/II aHR 2.17 [95% CI, 1.57–2.98]), and left ventricular ejection fraction (left ventricular ejection fraction ≤35% versus >50% aHR 2.34 [95% CI, 1.58–3.48]; left ventricular ejection fraction 36%–50% versus >50% aHR 2.98 [95% CI, 2.02–4.40]), while history of nonsustained ventricular tachycardia (aHR 2.38 [95% CI, 1.62–3.51]) and New York Heart Association class (III/IV versus I/II aHR 1.84 [95% CI, 1.22–2.78]) were strongly associated with hospitalization for ventricular arrhythmia/cardiac arrest.

Conclusions

Primary prevention ICD utilization in patients with hypertrophic cardiomyopathy increased over time, including among those ≥65 years old. Among older patients, the strongest risk factors for hospitalization for ventricular arrhythmia/cardiac arrest following ICD implantation were history of nonsustained ventricular tachycardia and New York Heart Association class.
Atherosclerosis Burden of Brain‐ and Heart‐Supplying Arteries and the Relationship With Vascular Risk in Patients With Ischemic Stroke
Authors: Kong Qi , Ma Xin , Li Luguang , Wang Chen , Du Xiangying , Wan Yungao
Published: August 2023

Background

Atherosclerosis of brain‐ and heart‐supplying arteries (BHAs) are risk indicators for patients with ischemic stroke, but the atherosclerosis burden (AB) of intracranial, cervical, aortic, and coronary arteries in each and in total have not been simultaneously evaluated, and the associations with vascular risk remain unknown.

Methods and Results

With computed tomography angiography, single‐territory AB was triple ranked on the basis of the number of arterial segments with a significant atherosclerotic lesion. The total AB (TAB) of BHAs was triple ranked on the basis of the number of arterial territories with a significant atherosclerotic lesion, or according to the sum of 4 single‐territory AB rank‐scores. After a 12‐month follow‐up of 395 patients with ischemic stroke, a composite outcome of ischemic stroke, myocardial infarction, and vascular death occurred in 10.9%. The single‐territory AB of intracranial, cervical, aortic, and coronary arteries showed distinct strata patterns and different associations with vascular risk. The score‐based TAB of BHAs predicted vascular risk (crude hazard ratios [95% CIs]: per level increase, 2.35 [1.54–3.58]; median versus low, 3.37 [1.45–7.82]; high versus low, 6.00 [2.36–15.24]) independently of vascular risk factors and single‐territory AB, providing more prognostic information than the TAB of BHAs measured by the number of significantly atherosclerotic territories. Vascular events occurred in 3.0%, 13.6%, and 22.6% of patients in the low (41.8%), median (44.8%), and high (13.4%) strata of the score‐based TAB of BHAs, respectively.

Conclusions

The single‐territory AB of intracranial, cervical, aortic, or coronary arteries might be not reliable for vascular risk stratification in patients with ischemic stroke, and evaluating the TAB of BHAs by quantitatively integrating the single‐territory AB is advisable.
Green Financial and Regulatory Policies: Why Are Some Central Banks Moving Faster than Others?
Authors: Gupta Bhavya , Cheng Ruijie , Rajan Ramkishen S.
Published: August 2023

Climate change poses financial risks to individual firms and is a source of systemic risk to the stability of financial systems. Central banks are emerging as key state actors in environmental governance to tackle these risks, implementing policies encompassing regulatory oversight, credit guidance, and the greening of prudential regulations. The diffusion of these policies across countries is at various stages of deliberation and implementation. In this context, this article uses a newly constructed index measuring the intensity of green financial and regulatory policies imposed by central banks of various developed and developing countries from 1996 through 2018. We empirically assess whether central banks in countries that are more vulnerable to climate change are more likely to be implementers of these policies and find robust evidence in support of our hypothesis.
Interrupting the Human: Shuffling
Authors: van Bever Donker Maurits
Published: August 2023

What does it mean to be adequate to a conjuncture? What, if anything, can such a project, and the failure thereof, teach us with regard to the work of freedom, and its time? In this paper, I suggest that “inaugurating postcolonial difference lodges difference not as a marker of identity … It is, instead, an ethics of response … [It] is, ultimately a possibility of reading.” It is Sylvia Wynter, throughout her oeuvre but most explicitly in her conversations with Katherine McKittrick, who posits a sense of the human that grasps it as a blending of “mythoi” and “bios”, of story and genetics. In this crucial framing for my intervention, being adequate means to always interrupt the narrative of the human: where one starts matters. The human functions as a ground for the articulation of, and claims to, particular rights. It is the human that claims freedom, and it is in the name of the human that the limits of these claims are also set out. As such, the paper offers “reading”, specifically a form of slow reading named as “shuffling”, which is gleaned from different scenes – among them the preambles and post-ambles of founding texts in South Africa’s transition from apartheid, and Biko’s court case – each of which add a new aspect to the “shuffle” by which a reading happens, as a method for exodus.
A regional analysis of the competitiveness of industries in the Nelson Mandela Bay Metropolitan Municipality, South Africa
Authors: Neethling Roan Jan , Kleynhans Ewert PJ , Mncayi Precious
Published: August 2023

The Nelson Mandela Bay Metropolitan Municipality is situated on the Eastern Coastline of South Africa. The metropolitan itself has the potential for major local and regional economic growth but has experienced significantly low growth over the past few years. Internal constraints that the province faces include high production costs, limited economic development and support, deteriorating infrastructure and limited financial resources. To assess the local economy of the Nelson Mandela Bay Metropolitan Municipality, the methodological techniques used include the location quotient and shift-share analysis. The empirical analysis showed that the municipality is highly specialised in industries such as agriculture, forestry and fishing, and transport equipment. The evaluation of the top five industries revealed that business services, wholesale and retail trade, transport and storage, catering and accommodation, and social and personal services have the highest growth potential and may contribute to future development initiatives. Efforts to stimulate industrial growth include the promotion of tourism, increasing the market share of wholesale and retail trade, establishing an integrated approach to the services industry, and finally, expanding the market share of the transport and storage industry.
Health literacy strengths and challenges of people in New South Wales prisons: a cross-sectional survey using the Health Literacy Questionnaire (HLQ)
Authors: Gill Scott , Zeki Reem , Kaye Sharlene , Zingirlis Panayiota , Archer Vicki , Lewandowski Amy , Creighton Grantley , Shaw Caron , Bowman Julia
Published: August 2023

Background

Health literacy is an important factor for enabling people to manage their health and live long fulfilling lives. People in prison are frequently from marginalised communities, often out of reach of conventional community based health organisations, and have poorer health outcomes. It is essential to understanding the health literacy profiles of people in prison, and its contribution to the well-established health inequities and outcomes of this population. This study aimed to use a multi-dimensional health literacy measurement tool to describe the strengths and challenges of adults incarcerated in NSW prisons.

Methods

A cross-sectional survey was conducted for people in prison across 14 publicly operated metropolitan prisons. Data were collected from 471 participants using the Health Literacy Questionnaire (HLQ). Participant characteristics and health conditions were also collected. Data were analysed using descriptive statistics. Effect sizes (ES) for standardised differences in means were used to describe the magnitude of difference between participant characteristic groups.

Results

Participants’ median age was 38.0 (range 19 – 91) years. Males comprised 81% of the sample, 21% identified as Aboriginal and/or Torres Strait Islander, and 53% reported a health problem. People in prison had lower scores for all nine HLQ scales when compared to the general Australian population. Small to medium ES were seen for mean differences between most demographic groups. Compared to males, females had lower scores for several of the HLQ scales including ‘having sufficient information to manage health’ (ES 0.30 [95% Confidence Interval (CI) 0.07, 0.53]), ‘ability to actively engage with health care professionals’ (ES 0.30 [95% CI 0.06, 0.53]), ‘navigating the healthcare system’ (ES 0.30 [95% CI 0.06, 0.53]), and, ‘ability to find good health information’ (ES 0.33 [95% CI 0.10, 0.57]). Differing health literacy scale scores with small to medium ES were found when comparing participants by legal status. Mainly small ES were seen when comparing other participant characteristic groups.

Conclusions

This study provides insights into the health literacy strengths and challenges for people in NSW prisons. These findings highlight the important role health literacy could have in addressing health disparities in this vulnerable population and can inform prison health services.
Association between systemic immune-inflammation index and chronic obstructive pulmonary disease: a population-based study
Authors: Ye Chenglin , Yuan Li , Wu Kailang , Shen Bingzheng , Zhu Chengliang
Published: August 2023

Background

The Systemic Immune-Inflammation Index (SII) is a quantitative measurement of the systemic immune-inflammatory response in the human body. The SII has been shown to have prognostic value in various clinical settings, including critical illness, sepsis, and cancer. Its role in chronic obstructive pulmonary disease (COPD) remains unclear and requires further investigation.

Methods

We analyzed demographic data from 16,636 participants in the National Health and Nutrition Examination Survey. Logistic regression analysis was performed to assess the correlation between COPD, lung function, chronic respiratory symptoms and SII. We used Cox proportional hazards (PH) model to analyze the relationship between SII and mortality in COPD patients and healthy individuals. We used propensity score matching (PSM) method to match the COPD population with similar baseline levels with the normal population to further analyze the correlation between SII and COPD.

Results

We recruited 16,636 participants, ages 40 and above, for the study. A multivariable logistic regression analysis revealed that a higher SII level was independently associated with an elevated likelihood of COPD (Odds Ratio (OR) = 1.449; 95% Confidence Interval (CI): 1.252–1.676, P < 0.0001) after controlling for all other factors. Results of subgroup analysis showed a significant positive correlation between SII and COPD in different age groups, gender, Body Mass Index, smoking status, and those with a history of hypertension. The SII index had positive correlation with COPD after PSM (OR = 1.673; 95%CI: 1.443–1.938). After full adjustment, an increase in the SII is associated with a higher all-cause mortality rate. The hazard ratio (HR) with a 95% CI in the general population, COPD patients, and healthy individuals are 1.161 (1.088, 1.239), 1.282 (1.060, 1.550), and 1.129 (1.055, 1.207), respectively.

Conclusions

Higher SII levels are linked to higher prevalence of COPD. COPD patients with a higher SII levels have a higher risk of all-cause mortality. Additional large-scale, long-term studies are necessary to confirm these results.
Nonlinear relationship between atherogenic index of plasma and the risk of prediabetes: a retrospective study based on Chinese adults
Authors: Zheng Xiaodan , Zhang Xin , Han Yong , Hu Haofei , Cao Changchun
Published: August 2023

Background

The atherogenic index of plasma (AIP) can reflect the burden of atherosclerosis. Hyperglycemia is one of the leading causes of atherosclerosis. However, the relationship between AIP and prediabetes is rarely studied. Therefore, we aimed to explore the relationship between AIP and prediabetes.

Methods

This retrospective cohort study recruited 100,069 Chinese adults at the Rich Healthcare Group from 2010 to 2016. AIP was calculated according to Log10 (triglyceride/high-density lipoprotein cholesterol) formula. Cox regression method, sensitivity analyses and subgroup analyses were used to examine the relationship between AIP and prediabetes. Cox proportional hazards regression with cubic spline functions and smooth curve fitting was performed to explore the non-linearity between AIP and prediabetes. The two-piece Cox proportional hazards regression model was used to determine the inflection point of AIP on the risk of prediabetes.

Results

After adjusting for confounding covariates, AIP was positively associated with prediabetes (HR: 1.41, 95%CI: 1.31–1.52, P < 0.0001). The two-piecewise Cox proportional hazards regression model discovered that the AIP’s inflection point was 0.03 (P for log-likelihood ratio test < 0.001). AIP was positively associated with the risk of prediabetes when AIP ≤ 0.03 (HR: 1.90, 95%CI: 1.66–2.16, P < 0.0001). In contrast, When AIP > 0.03, their association was not significant (HR: 1.04, 95%CI: 0.91–1.19, P = 0.5528).

Conclusion

This study shows that AIP was positively and non-linearly associated with the risk of prediabetes after adjusting for other confounding factors. When AIP ≤ 0.03, AIP was positively associated with the risk of prediabetes.
Local delivery of hrBMP4 as an anticancer therapy in patients with recurrent glioblastoma: a first-in-human phase 1 dose escalation trial
Authors: Bos Eelke M. , Binda Elena , Verploegh Iris S.C. , Wembacher Eva , Hoefnagel Daphna , Balvers Rutger K. , Korporaal Anne L. , Conidi Andrea , Warnert Esther A. H. , Trivieri Nadia , Visioli Alberto , Zaccarini Paola , Caiola Laura , van Wijck Rogier , van der Spek Peter , Huylebroeck Danny , Leenstra Sieger , Lamfers Martine L.M. , Ram Zvi , Westphal Manfred , Noske David , Legnani Federico , DiMeco Francesco , Vescovi Angelo Luigi , Dirven Clemens M.F.
Published: August 2023

Background

This Phase 1 study evaluates the intra- and peritumoral administration by convection enhanced delivery (CED) of human recombinant Bone Morphogenetic Protein 4 (hrBMP4) – an inhibitory regulator of cancer stem cells (CSCs) – in recurrent glioblastoma.

Methods

In a 3 + 3 dose escalation design, over four to six days, fifteen recurrent glioblastoma patients received, by CED, one of five doses of hrBMP4 ranging from 0·5 to 18 mg. Patients were followed by periodic physical, neurological, blood testing, magnetic resonance imaging (MRI) and quality of life evaluations. The primary objective of this first-in-human study was to determine the safety, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of hrBMP4. Secondary objectives were to assess potential efficacy and systemic exposure to hrBMP4 upon intracerebral infusion.

Results

Intra- and peritumoral infusion of hrBMP4 was safe and well-tolerated. We observed no serious adverse events related to this drug. Neither MTD nor DLT were reached. Three patients had increased hrBMP4 serum levels at the end of infusion, which normalized within 4 weeks, without sign of toxicity. One patient showed partial response and two patients a complete (local) tumor response, which was maintained until the most recent follow-up, 57 and 30 months post-hrBMP4. Tumor growth was inhibited in areas permeated by hrBMP4.

Conclusion

Local delivery of hrBMP4 in and around recurring glioblastoma is safe and well-tolerated. Three patients responded to the treatment. A complete response and long-term survival occurred in two of them. This warrants further clinical studies on this novel treatment targeting glioblastoma CSCs.

Trial registration

: ClinicaTrials.gov identifier: NCT02869243.
Lung abscess as a complication of Lemierre Syndrome in adolescents: a single center case reports and review of the literature
Authors: Venditto Laura , Ferrante Giuliana , Caccin Anna , Franchini Giulia , Zaffanello Marco , Tenero Laura , Piazza Michele , Di Gioia Stefano , Piacentini Giorgio , Pietrobelli Angelo
Published: August 2023

Background

Fusobacterium necrophorum is an anaerobic, gram-negative, non-motile, filamentous, non-spore forming bacillus found in the oral cavity, gastrointestinal tract, and female genital tract, responsible of a rare disease named Lemierre Syndrome, characterized by septic thrombophlebitis of the internal jugular vein, which mainly affects previously healthy adolescents and young adults; some risk factors are reported, as smoking or primary viral or bacterial infection leading to the disruption of mucosa. The syndrome originates commonly from an upper respiratory infection such as pharyngotonsillitis, acute otitis media, cervical lymphadenitis, sinusitis, or odontogenic abscess, and may result in multiorgan metastasis, more frequently leading to pulmonary complications, especially lung abscesses.

Case presentation

We describe two cases of adolescents with atypical Lemierre Syndrome evaluated in a tertiary care center, one with a confirmed infection by Fusobacterium necrophorum and one with a presumptive diagnosis based on clinical features, who developed lung abscesses needing a prolonged antibiotic course and hospitalization. Of interest, both were user of electronic cigarette, configuring a possible new risk factor. The proper diagnosis of Lemierre Syndrome is often difficult to establish, so a high degree of suspicion is needed, especially in the case of lung abscesses in otherwise healthy adolescents.

Conclusion

The current study will contribute to providing insight into Lemierre Syndrome clinical presentation and management in adolescents, promoting awareness for a rare but potentially fatal disease. Moreover, it suggests a possible relationship between Lemierre syndrome and the use of electronic cigarette, that should be investigated by future studies.
Introduction of a multiplex amplicon sequencing assay to quantify DNA methylation in target cytosine markers underlying four selected epigenetic clocks
Authors: Pośpiech Ewelina , Pisarek Aleksandra , Rudnicka Joanna , Noroozi Rezvan , Boroń Michał , Masny Aleksander , Wysocka Bożena , Migacz-Gruszka Kamila , Lisman Dagmara , Pruszkowska-Przybylska Paulina , Kobus Magdalena , Szargut Maria , Dowejko Joanna , Stanisz Kamila , Zacharczuk Julia , Zieliński Piotr , Sitek Aneta , Ossowski Andrzej , Spólnicka Magdalena , Branicki Wojciech
Published: August 2023

Background

DNA methylation analysis has proven to be a powerful tool for age assessment. However, the implementation of epigenetic age prediction in diagnostics or routine forensic casework requires appropriate laboratory methods. In this study, we aimed to compare the performance of large-scale DNA methylation analysis protocols that show promise in terms of accuracy, throughput, multiplexing capacity, and high sensitivity.

Results

The protocols were designed to target a predefined panel of 161 genomic CG/CA sites from four known estimators of epigenetic age-related parameters, optimized and validated using artificially methylated controls or blood samples. We successfully targeted 96% of these loci using two enrichment protocols: Ion AmpliSeq™, an amplicon-based method integrated with Ion Torrent S5, and SureSelectXT Methyl-Seq, a hybridization-based method followed by MiSeq FGx sequencing. Both protocols demonstrated high accuracy and robustness. Although hybridization assays have greater multiplexing capabilities, the best overall performance was observed for the amplicon-based protocol with the lowest variability in DNA methylation at 25 ng of starting DNA, mean observed marker coverage of ~ 6.7 k reads, and accuracy of methylation quantification with a mean absolute difference between observed and expected methylation beta value of 0.054. The Ion AmpliSeq method correlated strongly with genome-scale EPIC microarray data (R = 0.91) and showed superiority in terms of methylation measurement accuracy. Method-to-method bias was accounted for by the use of linear transformation, which provided a highly accurate prediction of calendar age with a mean absolute error of less than 5 years for the VISAGE and Hannum age clocks used. The pace of aging (PoAm) and the mortality risk score (MRS) estimators included in our panel represent next-generation clocks, were found to have low to moderate correlations with the VISAGE and Hannum models (R < 0.75), and thus may capture different aspects of epigenetic aging.

Conclusions

We propose a laboratory tool that allows the quantification of DNA methylation in cytosines underlying four different clocks, thus providing broad information on epigenetic aging while maintaining a reasonable number of CpG markers, opening the way to a wide range of applications in forensics, medicine, and healthcare.
Willingness to use novel reversible methods of male birth control: a community-based survey of cisgender men in the United States
Authors: Martins Summer L. , Boraas Christy M.
Published: August 2023

Background

There is high global demand for new methods of male birth control (MBC). However, contemporary evidence regarding men’s method-specific attitudes and their determinants is sparse.

Methods

Non-sterilized cisgender men ages 18–45 with recent history of female sex partners were surveyed at a large community event in the Midwestern US. We examined variation in participants’ willingness to use MBC by method (gel, pill, injection, implant, and vas occlusion), potential side effects, and potential barriers. We estimated crude and adjusted prevalence ratios (aPRs) for associations between participant characteristics and willingness to use ≥ 1 MBC method.

Results

Overall, 72% of participants (n = 187; mean age, 29) were very willing to use ≥ 1 MBC method although support for individual methods ranged widely from 62% (pill) to 24% (vas occlusion). In bivariate analysis of sociodemographic and health characteristics, few demonstrated associations with MBC willingness. In a multivariable model, willingness was independently related to age (30–39 vs. 18–29 years old, aPR = 1.24, 95% CI 1.04–1.48) and having ever been tested for HIV (aPR = 1.27, 95% CI 1.07–1.51). Willingness to tolerate side effects was < 10% for most items. The most commonly endorsed barriers to MBC use were high cost (77%) and side effects (66%).

Conclusions

Enthusiasm for MBC was high but waned in the context of potential side effects and barriers. Additional research on MBC attitudes in socioeconomically and culturally diverse populations worldwide is sorely needed.
Pathogenicity and other characteristics of the endophytic Beauveria bassiana strain (Bals.) (Hypocreales: Cordycipitaceae)
Authors: El-Maraghy Saad S. Mohamed , Abdel-Rahman Mohamed A. A. , Hassan Shimaa Hassan Mohamed , Hussein Khalid A.
Published: August 2023

Background

Agriculture crops such as tomatoes and wheat are frequently targeted by insect pests which have a significant negative impact on the agricultural economies. The deployment of entomopathogenic fungi (EPF) for the control of the insect pests is an important alternative to synthetic insecticides. The EPF, Beauveria bassiana (Balsamo) Vuillemin, has been reported widely as a suitable biological control agent of many agricultural pests.

Results

In this study, B. bassiana SS-1 was isolated from local plant crops and its pathogenicity was assessed against the greater wax moth larvae Galleria mellonella (L.). The development of the pathogenic B. bassiana SS-1 on the insect was visualized using scanning electron microscopy (SEM). Results showed the ability of B. bassiana SS-1 to secrete extracellularly the important enzymes essential for insect cuticle penetration. B. bassiana SS1 recorded the maximum mean lipase (5.3 U/ml), protease (32.13 U/ml), and chitinase activities (2.95 U/ml). The endophytic pathogenic fungus B. bassiana SS-1 demonstrated pathogenicity against the fourth instar larvae of G. mellonella showing LC50 at 2.47 × 102 conidia/ml and LC95 at 3.98 × 105 conidia/ml. The SEM results showed physical contact with B. bassiana SS-1 hyphae on the surface of the G. mellonella larvae. Thus, the isolated EPF B. bassiana SS-1, even endophytic, could be a promising biocontrol agent to manage agricultural insect pests.

Conclusion

This study provided a comprehensive characterization of the pathogenicity of B. bassiana SS-1 with its microbiological characteristics. Future studies are needed to focus on the detection of highly virulent isolates against different insect pests and to assess their field contribution as a favorable biological control agent.
Anaplastic Lymphoma Kinase Inhibitors for Therapy of Neuroblastoma in Adults
Authors: Stiefel Jessica , Kushner Brian H. , Roberts Stephen S. , Iglesias-Cardenas Fiorella , Kramer Kim , Modak Shakeel
Published: August 2023

PURPOSE

Adult-onset neuroblastoma (AON) differs significantly in biology and clinical behavior from childhood-onset disease. AON poses therapeutic challenges since tolerance of intensive multimodality therapies that are standard of care for pediatric neuroblastoma (NB) is poor. AON is enriched for somatic mutations including anaplastic lymphoma kinase ( ALK), deemed to be an oncogenic driver in NB. ALK inhibitors (ALKis), therefore, have the potential to be of therapeutic benefit. The purpose of this study is to report on their use in AON.

METHODS

A single-center retrospective review of adults with NB receiving ALKi (2012-2022) was performed. Response was evaluated using International Neuroblastoma Response Criteria.

RESULTS

Fifteen patients with ALK-mutated AON were treated with US Food and Drug Administration–approved ALKi starting at a median age of 34 (16-71) years. Initial ALKi was lorlatinib, crizotinib, and alectinib in seven, five, and three patients respectively; seven received multiple ALKis due to progressive disease/intolerability of one agent. All patients experienced ≥grade 2 adverse events (AEs): crizotinib and alectinib were associated primarily with gastrointestinal AEs, lorlatinib with neurologic AEs, weight gain, and hyperlipidemia resulting in dose reduction or discontinuation of ALKi in several patients. No responses were observed with crizotinib (n = 5 patients), ceritinib, alectinib, or brigatinib (n = 1 each). Of the 13 patients receiving lorlatinib, four, five, and four patients had a complete or partial response (major response rate 69%), and stable disease, respectively. Responses were noted in all disease compartments; complete metabolic response was seen in two L2 patients. Ten of 13 patients remain progression-free at a median of 19 (6-50) months on lorlatinib. Three (two receiving dose-reduced therapy) had progressive disease. Median survival from start of first ALKi was 43 ± 26 months.

CONCLUSION

ALKis, particularly lorlatinib, are effective treatment options for AON. However, AEs necessitating dose reduction are common.
The Ethos of Distance in Emotional Culture Critiques: Helmuth Plessner, Richard Sennett, Frank Furedi
Authors: Kolkenbrock Marie
Published: August 2023

Although COVID-19 gave “social distancing” an omnipresent urgency, the concept of distance—in its spatial meaning and in its metaphorical use for emotional detachment, interpersonal boundaries, and socially constructed difference—has been central to theories, practices, and ethics of modern sociability. This article argues that the sociological critique of modern therapeutic culture deploys a specific ethos of distance, which is shown through the work of Richard Sennett and Frank Furedi. Sennett and Furedi reactualize intellectual debates around the regulation of emotional exposure and vulnerability reminiscent of the “codes of cool conduct” in the culture of Weimar Germany, which Helmut Lethen has famously conceptualized based on the philosophical anthropology of Helmuth Plessner. Drawing on Sara Ahmed’s work, the article argues that this Plessnerian ethos of distance, while ostensibly designed to guarantee just and pluralistic societies, reproduces social hierarchies of political emotions and in this way prioritizes the stability of the current system and social cohesion over justice.
Effects of Single-Stranded DNA Base Number and Duplex DNA Formation on Intraparticle Diffusion Behavior
Authors: Miyagawa Akihisa , Fukushima Asahi , Nagatomo Shigenori , Nakatani Kiyoharu
Published: August 2023

We investigated the effects of the base number of single-stranded DNA and duplex DNA formation on the intraparticle diffusion behavior in amino-functionalized silica particles. The sigmoidal distribution behavior of 50 base single-stranded DNA was explained using the DNA aggregation model. Similar results to those previously reported using 20 base DNA were obtained. However, the DNA aggregate was less likely to form and the diffusion coefficient (D) decreased likely because of electrostatic repulsion and pore hindrance, respectively. The intraparticle diffusion of the duplex DNA participated in its dissociation. After duplex DNA distribution in the particle, the single-stranded DNA formed in solution inside the pores was released. The D values ((3.5–8.1) × 10−8 cm2 s−1) obtained from the initial rate were 10-fold those of single-stranded DNA ((0.69–5.0) × 10−9 cm2 s−1). Therefore, the distribution mechanisms of longer single-stranded and duplex DNA were revealed based on the kinetic analysis.
“This Land Is Your Land”: A Note on America as a Nation of “Varied Carols”
Authors: Detering Heinrich
Published: August 2023

Modern American literature starts with the sound of voices singing: “I hear America singing, the varied carols I hear”. It is Walt Whitman who begins one of his most popular poems with this line, referring to the voices of people from all generations, classes and ethnic backgrounds who are about to form a new type of nation, a nation beyond ethnicity based on the principles of democracy and diversity alone. Against this background of listening to the countless different voices, his equally famous poem ‘America’ reads like a personal and individual answer: “Centre of equal daughters, equal sons, / All, all alike endear’d, grown, ungrown, young or old, / Strong, ample, fair, enduring, capable, rich”. Whitman’s poetry lays out the foundation for a specifically American tradition of song poetry that focuses on political equality and social justice as collective human rights and the free development of every person’s individuality at the same time. The present article follow the line from Whitman’s poetry of songs to 20th century American song poetry, by the way of the example of Woody Guthrie’s anthem ‘This Land Is Your Land’ and its transformative receptions in Bob Dylan’s and Bruce Springsteen’s adaptations (in contrast to the way in which European national anthems conceive the nation-as-territory).