bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics Associated with the Use of Diagnostic Prostate Biopsy and Biopsy Outcomes in Australian Men
Authors: Chiam Karen , Bang Albert , Patel Manish I. , Nair-Shalliker Visalini , O’Connell Dianne L. , Smith David P. 
Published: June 2021

Abstract

Background:
Population characteristics associated with the use of prostate biopsy are poorly understood. We described the use of diagnostic prostate biopsy and subsequent biopsy outcomes in a population-based Australian cohort.

Methods:
A total of 91,764 men from the Sax Institute's 45 and Up Study (New South Wales, Australia) recruited during 2006 to 2009 were included. Self-completed baseline questionnaires and linked administrative health data were used. Study period was from the date of recruitment to December 2013. Cox regression and logistic regression identified factors associated with receipt of biopsy and subsequent prostate cancer diagnosis.

Results:
During the study period, 5,089 participants had a diagnostic prostate biopsy, and 2,805 men (55.1% of those biopsied) received a cancer diagnosis. Men with a family history of prostate cancer (HR 1.55; 95% confidence interval (CI), 1.43–1.68), severe lower urinary tract symptoms (HR 1.62; 95% CI, 1.41–1.86), or a record of medication for benign prostatic hyperplasia (HR 1.34; 95% CI, 1.23–1.47) had increased risks of receiving a biopsy. Men with a family history of prostate cancer had increased odds of a positive biopsy (OR 1.21; 95% CI, 1.01–1.43). High alcohol consumption (≥21 drinks per week compared with 1–6 drinks per week) was associated with decreased risk of biopsy (HR 0.88; 95% CI, 0.80–0.96) but increased odds of a positive biopsy (OR 1.63; 95% CI, 1.32–2.02).

Conclusions:
Certain characteristics are associated with both undertaking diagnostic prostate biopsy and positive biopsy outcomes.

Impact:
This highlights the need to improve management of specific groups of men, especially those with clinical symptoms that overlap with prostate cancer, in their investigation for prostate cancer.
HPV-Induced Oropharyngeal Squamous Cell Carcinomas in Brazil: Prevalence, Trend, Clinical, and Epidemiologic Characterization
Authors: Santos Carvalho Raiany , Scapulatempo-Neto Cristovam , Curado Maria Paula , de Castro Capuzzo Renato , Marsico Teixeira Fernanda , Cardoso Pires Rafael , Cirino Maria Thereza , Cambrea Joaquim Martins Jessica , Almeida Oliveira da Silva Isabella , Oliveira Marco Antonio , Watanabe Marcel , Guimarães Ribeiro Adeylson , Caravina de Almeida Gisele , Reis Rui Manuel , Ribeiro Gama Ricardo , Lopes Carvalho André , de Carvalho Ana Carolina 
Published: June 2021

AbstractBackground:Tobacco or human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCC) represent different clinical and epidemiologic entities. This study investigated the prevalence of HPV-positive and HPV-negative OPSCC in a reference cancer hospital in Brazil and its association with clinical and demographic data, as well as its impact on overall survival.Methods:HPV infection was determined by p16-IHC in pre-treatment formalin-fixed paraffin-embedded samples from all patients with OPSCC diagnosed at Barretos Cancer Hospital between 2008 and 2018. The prevalence of HPV-positive cases and its temporal trend was assessed, and the association of clinical and demographic data with HPV infection and the impact on patient overall survival was evaluated.Results:A total of 797 patients with OPSCC were included in the study. The prevalence of HPV-associated tumors in the period was 20.6% [95% confidence interval, 17.5–24.0] with a significant trend for increase of HPV-positive cases over the years (annual percentage change = 12.87). In a multivariate analysis, the variables gender, level of education, smoking, tumor sublocation, region of Brazil, and tumor staging had a significant impact in HPV positivity, and a greater overall survival (OS) was observed in HPV-positive patients (5-year OS: 47.9% vs. 22.0%; P = 0.0001).Conclusions:This study represents the largest cohort of Brazilian patients with OPSCC characterized according to HPV status. We report significant differences in demographics and clinical presentation according to HPV status, and an increasing trend in prevalence for HPV-induced tumors.Impact:These findings can potentially contribute to a better stratification and management of patients as well as assist in prevention strategies.
СИСТЕМА ВПРАВ ДЛЯ ВИВЧЕННЯ ГРАМАТИЧНИХ КАТЕГОРІЙ ЧАСУ ТА ОСОБИ ДІЄСЛІВ РУХУ НА ЗАНЯТТЯХ ІЗ ДИСЦИПЛІНИ «УКРАЇНСЬКА МОВА ЯК ІНОЗЕМНА» (НА ПРИКЛАДІ ТЕМИ «У МІСТІ. УРОК 2»)
Authors: Руденко М. І. 
Published: June 2021

Перед викладачами української мови як іноземної сьогодні стоїть непросте завдання − відібрати з усього обширу лексичного багатства та граматичних парадигм ті, які позначені найбільшою вживаністю і, відтак, є найбільш необхідними для вивчення. Здійснюючи це на практиці, лінгводидакти перебувають у стані постійного пошуку нових підходів до навчання, нетривіальних методик викладання. Адже кінцевим результатом опанування курсу «Українська мова як іноземна» повинна стати людина з вільними навичками спілкування в чужомовному для неї середовищі.
У статті запропоновано апробоване заняття з дисципліни «Українська мова як іноземна» на тему «У місті. Урок 2». Оскільки Урок 1 і Урок 2 складають тематичну цілісність, на другому занятті продовжується робота із локативною лексикою. Перший блок вправ призначений для активного залучення у розмову студентів із застосуванням вивченої урбаністичної лексики та опрацюванням нових слів. Із застосуванням мультимедійних технологій останні покращують комунікативні навички, розмовляючи про побачене. Тема визначила опрацювання таких граматичних категорій, як особа, час та рід одновидових дієслів руху – іти/ходити, їхати/їздити, а відтак − їхньої сполучуваності з локативними іменниками та прислівниками. Вживання цих дієслів у контексті продемонстровано на прикладі діалогів, які відтворюють звичні для студентів ситуації з повсякденного життя.
Граматичні форми дієслів систематизовано за допомогою таблиці, у якій суміщено граматичні категорії особи, часу та роду. Це дозволяє візуалізувати одну з найскладніших тем для вивчення та актуалізувати вже вивчені знання про дієслово. Навички використання правильних грамем є дуже важливими для подальшого ефективного комунікування в іншомовному середовищі, особливо в професійному мовленні.
Система тренувальних вправ покликана сформувати розуміння семантичної різниці у змісті пар слів іти/ходити, їхати/їздити, відтак вміння застосовувати особові форми дієслів у реченні, також диференціювати їх у часовій площині. Зміст вправ дозволяє також пригадати попередні граматичні теми, зокрема рід іменника. Читання діалогів закріплює розуміння контекстуального вживання вивченого. Результатом заняття вбачаємо вільне оперування опрацьованим на занятті лексико-граматичним матеріалом у повсякденному та професійному спілкуванні.
Homens da Montanha: Cristãos Novos e a Ocupação do Interior Brasileiro
Authors: Tonello Levy Daniela 
Published: June 2021

Judeus Sefaraditas, descendentes dos convertidos em 1497, foram os pioneiros na descoberta do ouro e diamantes na América portuguesa. A instituição do Tribunal do Santo Ofício da Inquisição, trouxe drásticas consequências para a vida Ibérica, que a longo prazo arruinaram o comércio português, fazendo emigrar do Reino os mais prestigiosos elementos, prejudicando por muitos anos a produção nacional, destruindo famílias e negócios. A cultura judaica, florescente na Península Ibérica até o século XV, apagou-se, e Portugal submergiu nas trevas da ignorância. Em São Paulo, os cristãos novos estiveram entre os desbravadores do sertão brasileiro, ultrapassando os limites do Tratado de Tordesilhas. Os habitantes da então inóspita Vila de São Paulo de Piratininga eram considerados inimigos da Espanha, por suas incursões ao sertão em busca de oportunidades econômicas. No interior, lutaram contra às Missões jesuíticas, a vida selvagem, fome, sede e finalmente se tornaram os primeiros a encontrar ouro no Brasil. Foram os primeiros a abrir estradas e fundar as vilas do ouro. Um marrano, Garcia Rodrigues Paes, foi o responsável pela construção do “Caminho do comércio” que encurtava a distância entre o Rio de janeiro, principal porto e a Vila de Ouro Preto. Os sefaraditas acreditavam estar seguros, nas montanhas e no interior do Brasil, mas a Inquisição formou uma rede de espiões encarregados de espionar e prender os cristãos novos.
Abstract 137: Thromboinflammatory Response in Patients Undergoing Transcatheter Aortic Valve Replacement Using the Sapien Xt or CoreValve
Authors: Sexton Travis R , Liu John , Smyth Susan S 
Published: June 2021

Transcatheter aortic valve replacement (TAVR) has been increasingly used to treat patients with symptomatic aortic stenosis. Despite the evolution of the valves and their deployment, patients that have undergone TAVR continue to be at high risk for major adverse events following the procedure. We recently reported that TAVR elicits a thromboinflammatory state that may contribute to the observed post-procedural thrombocytopenia associated with worse clinical outcomes. With the approval of the newer generation valves and delivery systems, we have now compared thromboinflammatory responses in patients receiving the Medtronic CoreValve and Edward’s new SAPIEN XT valve.
Blood cell numbers, platelet function, and biomarkers of systemic inflammation and thrombosis were analyzed in 34 sequential patients undergoing transcatheteraortic valve replacement with the Edward’s SAPIEN XT valve or the Medtronic CoreValve Following valve deployment, platelet count, platelet activity, and platelet factor 4 levels decreased, while the inflammatory marker interleukin-6 increased. There were no significant differences in any of the parameters between the two valve types. Interestingly, baseline inflammation status predicted the extent of thrombocytopenia observed in overall cohort.
A comparions of the SAPIENT XT valve and the Medtronic CoreValve reveals that the new generation valves generate a lower inflammatory response than that observed in the older SAPIEN valce. Importantly, our results add to the growing body of literature that suggests the thromboinflammatory changes that occur early after TAVR may predict long-term outcomes and suggest potential beneficial effects of an anti-inflammatory strategic.
Abstract 149: Analysis of Radiotherapy Induced Vascular Lesions Reveals Potential Therapies Against Innate Inflammation in an ApoE Knockout Mouse Model
Authors: Christersdottir Tinna , Pirault John , Lundberg Anna M , Yan Zhong-Qun , Paulsson-Berne Gabrielle , Hansson Göran K , Halle Martin 
Published: June 2021

Clinical studies show an increase risk for cardiovascular disease (CVD) at the site of irradiation years after exposure. Radiotherapy together with other cancer therapies contributes to a growing population of cancer survivors in risk of developing radiotherapy induced vascular disease. However, traditional treatments for CVD such as thrombolytic inhibitors and lipid lowering drugs (statins) seem to have no effect on radiation induced vascular disease in mouse models. We have previously demonstrated a sustained chronic inflammation by NF-kB activation in irradiated human arteries. To further investigate radiation induced vascular disease and potential therapies against innate inflammation, we established a mouse model of local irradiation in an atherosclerotic prone ApoE-/- background. ApoE-/- mice fed chow diet were exposed to a single dose of 0 Gy (sham/controls) or 14 Gy at the upper chest and neck area and harvested 10 weeks later. Plasma, thoracic aorta, aortic arch, heart were retrieved and taken for plasma, blood count, en face, mRNA, immunohistochemistry and immunofluorescence analysis. Irradiated mice presented higher total plasma cholesterol levels than controls. En face analysis of aortic arches showed a decreased percentage of lesion size in irradiated arteries compared to controls. However, an increase of MHC class II (IA-b) staining in irradiated aortic roots suggested an induction of inflammation in the context of radiotherapy. These data were supported by the quantification of monocyte chemotactic protein 1 mRNA expression in the thoracic aorta showing a significant increase in irradiated animals compared to unirradiated (p≤0,001).
The current data demonstrated that radiotherapy induces a macrophage-rich and inflamed plaque that may explain the increased risk of developing severe clinical events i.e. myocardial infarction or stroke. Further analyses of this partial irradiation mouse model are on-going to assess the potential therapeutic targets involved in innate immunity and NF-kB activation. Results of currently performed therapeutic experiments will be further presented.
Abstract 168: YAP and TAZ Mediate Mechanical Control of Vasculogenesis
Authors: Mason Devon E , Voytik-Harbin Sherry L , Yoder Mervin C , Boerckel Joel D 
Published: June 2021

Physical cues such as the mechanical properties of the extracellular matrix are known to modulate blood vessel formation, but the underlying mechanisms remain poorly understood.
Yes-associated protein (YAP) and transcriptional activator with PDZ-binding domain (TAZ) were recently identified as key mediators of cellular mechanotransduction [1], but the roles of YAP and TAZ in neovascular mechanobiology have not been investigated.
We hypothesized that YAP and TAZ mediate neovascular mechanotransduction of extracellular matrix rigidity by vasculogenic endothelial colony forming cells (ECFCs) cultured on/in matrices of controllable rigidity.
YAP and TAZ depletion abrogated ECFC migration (Fig. 1A), and YAP/TAZ expression and nuclear localization (i.e., activation) was significantly upregulated in migrating cells (Fig. 1B). Combinatorial depletion also abrogated tubular network formation and 3D vasculogenesis in collagen matrices of variable rigidity but constant matrix density (data not shown). In 2D, PDMS rigidity regulated YAP/TAZ subcellular localization (data not shown). In 3D, vasculogenesis was enhanced in stiff (G’= 1049 Pa) collagen oligomer matrices compared to soft (G’ = 305 Pa) monomer matrices formulated at constant collagen matrix density. YAP and TAZ were nuclear localized (activated) in the stiff oligomer matrices, but cytosolic in soft monomer matrices (Fig. 1C). Mechanistically, YAP and TAZ depletion reduced cytoskeletal stress fiber formation (data not shown), implicating YAP and TAZ in a feedback mechanism to control cytoskeletal remodeling.

Delivered in oligomer matrices
in vivo
, ECFCs formed a functional human neovascular plexus and exhibited strong expression and nuclear localization of YAP and TAZ and expression of downstream genes, Cyr61 and CTGF (data not shown).

In summary, YAP and TAZ are essential for mechanical control of ECFC migration and vasculogenesis.
[1] Dupont et al. 2011 Nature. 474:179-185.
Abstract 602: Development of Cell Therapy in Severe Familial Hypercholesterolemia
Authors: Koseki Masahiro , Saga Ayami , Kobayashi Takuya , Asaji Masumi , Okada Takeshi , Kawase Ryota , Tomita Koichi , Osuga Keigo , Ezoe Sachiko , Nishida Makoto , Sakata Yasushi , Yamashita Shizuya 
Published: June 2021

Familial hypercholesterolemia (FH) patients are characterized by high LDL cholesterol levels in the blood and premature cardiovascular disease. Although most of heterozygous FH patients are able to be treated with statin, ezetimibe and bile acid sequestrants and anti-PCSK9 antibodies, homozygous FH patients are resistant to drug therapy. Therefore, many of homozygous FH patients used to be treated by LDL-apheresis. However, the effect of removing LDL cholesterol is still not sufficient and definitive therapies need to be developed.
With the increase of the evidence about the safety of mesenchymal stem cells and percutaneous transhepatic portal approach in islet transplantation, we have developed a cell transplantation therapy with allogeneic adipose tissue-derived multilineage progenitor cells, as an alternative treatment instead of liver transplantation.
We have generated a protocol for the phase 1 clinical study. The primary endpoint should be safety evaluation including allergic reaction, rejection reaction, thrombosis and complications in the blood vessel by cell-transplantation. The secondary endpoint should be the efficacy including changes in serum lipid such as LDL-C, TC, HDL-C, TG and Lp(a), and Secession possibility of LDL-apheresis.
We transplanted the first case in February, 2016. Then we are collecting clinical data. We would demonstrate the current status and the issues to be solved for the following study.
Improving the Effectiveness of Psychological Interventions for Depression and Anxiety in Cardiac Rehabilitation: PATHWAY—A Single-Blind, Parallel, Randomized, Controlled Trial of Group Metacognitive Therapy
Authors: Wells Adrian , Reeves David , Capobianco Lora , Heal Calvin , Davies Linda , Heagerty Anthony , Doherty Patrick , Fisher Peter 
Published: June 2021

Background:
Depression and anxiety in cardiovascular disease are significant, contributing to poor prognosis. Unfortunately, current psychological treatments offer mixed, usually small improvements in these symptoms. The present trial tested for the first time the effects of group metacognitive therapy (MCT; 6 sessions) on anxiety and depressive symptoms when delivered alongside cardiac rehabilitation (CR).

Methods:
A total of 332 CR patients recruited from 5 National Health Service Trusts across the North-West of England were randomly allocated to MCT+CR (n=163, 49.1%) or usual CR alone (n=169, 50.9%). Randomization was 1:1 via minimization balancing arms on sex and Hospital Anxiety and Depression Scale scores within hospital site. The primary outcome was Hospital Anxiety and Depression Scale total after treatment (4-month follow-up). Secondary outcomes were individual Hospital Anxiety and Depression Scales, traumatic stress symptoms, and psychological mechanisms including metacognitive beliefs and repetitive negative thinking. Analysis was intention to treat.

Results:

The adjusted group difference on the primary outcome, Hospital Anxiety and Depression Scale total score at 4 months, significantly favored the MCT+CR arm (–3.24 [95% CI, –4.67 to –1.81],
P
<0.001; standardized effect size, 0.52 [95% CI, 0.291 to 0.750]). The significant difference was maintained at 12 months (–2.19 [95% CI, –3.72 to –0.66],
P
=0.005; standardized effect size, 0.33 [95% CI, 0.101 to 0.568]). The intervention improved outcomes significantly for both depression and anxiety symptoms when assessed separately compared with usual care. Sensitivity analysis using multiple imputation of missing values supported these findings. Most secondary outcomes favored MCT+CR, with medium to high effect sizes for psychological mechanisms of metacognitive beliefs and repetitive negative thinking. No adverse treatment-related events were reported.

Conclusions:
Group MCT+CR significantly improved depression and anxiety compared with usual care and led to greater reductions in unhelpful metacognitions and repetitive negative thinking. Most gains remained significant at 12 months. Study strengths include a large sample, a theory-based intervention, use of longer-term follow-up, broad inclusion criteria, and involvement of a trials unit. Limitations include no control for additional contact as part of MCT to estimate nonspecific effects, and the trial was not intended to assess cardiac outcomes. Nonetheless, results demonstrated that addition of the MCT intervention had broad and significant beneficial effects on mental health symptoms.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: ISRCTN74643496.
Metabolomics Analysis Reveals Deranged Energy Metabolism and Amino Acid Metabolic Reprogramming in Dogs With Myxomatous Mitral Valve Disease
Authors: Li Qinghong , Larouche‐Lebel Éva , Loughran Kerry A. , Huh Terry P. , Suchodolski Jan S. , Oyama Mark A. 
Published: June 2021

Background
Myxomatous mitral valve disease (MMVD), a naturally occurring heart disease, affects 10% to 15% of the canine population. Canine MMVD shares many similarities with human MMVD. Untargeted metabolomics was performed to identify changes in metabolic pathways and biomarkers with potential clinical utilities.

Methods and Results

Serum samples from 27 healthy, 22 stage B1, 18 stage B2 preclinical MMVD dogs, and 17 MMVD dogs with a history of congestive heart failure (CHF) were analyzed. Linear regression analysis identified 173 known metabolites whose concentrations were different among the 4 groups (adjusted
P
<0.05), of which 40% belonged to amino acid super pathways, while 30% were lipids. More than 50% of significant metabolites were correlated with left atrial diameter but not left ventricular dimension. Acylcarnitines, tricarboxylic acid cycle intermediates, and creatine accumulated in proportion to MMVD severity. α‐Ketobutyrate and ketone bodies were increased as MMVD advanced. Nicotinamide, a key substrate of the main nicotinamide adenine dinucleotide (NAD
+
) salvage pathway, was decreased, while quinolinate of the de novo NAD
+
biosynthesis was increased in CHF dogs versus healthy dogs. 3‐Methylhistidine, marker for myofibrillar protein degradation, was higher in CHF dogs than non‐CHF dogs. Trimethylamine N‐oxide (TMAO) and TMAO–producing precursors, including carnitine, phosphatidylcholine, betaine, and trimethyllysine, were increased in CHF dogs versus non‐CHF dogs. Elevated levels of uremic toxins, including guanidino compounds, TMAO, and urea, were observed in CHF dogs. Pathway analysis highlighted the importance of bioenergetics and amino acid metabolism in canine MMVD.

Conclusions
Our study revealed altered energy metabolism, amino acid metabolic programming, and reduced renal function in the development of MMVD and CHF. Complex interplays along the heart‐kidney‐gut axis were implicated.