bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of advanced technology in the detection of sight-threatening eye disease in a UK community setting
Authors: Fidalgo Bruno R , Dabasia Priya , Jindal Anish , Edgar David F , Ctori Irene , Peto Tunde , Lawrenson John G 
Published: December 2019

Background/aimsTo determine the performance of combinations of structural and functional screening tests in detecting sight-threatening eye disease in a cohort of elderly subjects recruited from primary care.Methods505 subjects aged ≥60 years underwent frequency doubling technology (FDT) perimetry, iVue optical coherence tomography (iWellness and peripapillary retinal nerve fibre layer (RNFL) scans) and intraocular pressure with the Ocular Response Analyzer, all performed by an ophthalmic technician. The reference standard was a full ophthalmic examination by an experienced clinician who was masked to the index test results. Subjects were classified as presence or absence of sight-threatening eye disease (clinically significant cataract, primary open-angle glaucoma, intermediate or advanced age-related macular degeneration and significant diabetic retinopathy). Univariate and multivariate logistic regression analyses were used to determine the association between abnormal screening test results and the presence of sight-threatening eye disease.Results171 subjects (33.8%) had one or more sight-threatening eye diseases. The multivariate analysis found significant associations with any of the target conditions for visual acuity of <6/12, an abnormal FDT and peripapillary RNFL thickness outside the 99% normal limit. The sensitivity of this optimised screening panel was 61.3% (95% CI 53.5 to 68.7), with a specificity of 78.8% (95% CI 74.0 to 83.1), a positive predictive value of 59.5% (95% CI 53.7 to 65.2) and an overall diagnostic accuracy of 72.9% (95% CI 68.8 to 76.8).ConclusionsA subset of screening tests may provide an accurate and efficient means of population screening for significant eye disease in the elderly. This study provides useful preliminary data to inform the development of further larger, multicentre screening studies to validate this screening panel.
Effects of mirror training on motor performance in healthy individuals: a systematic review and meta-analysis
Authors: Chen Yinglun , Wang Pu , Bai Yulong , Wang Yuyuan 
Published: December 2019

ObjectiveMirror training (MTr) is a rehabilitation technique for patients with neurological diseases. There is no consensus on its effects on motor function in healthy individuals. This systematic review and meta-analysis considers the effects of MTr on motor function in healthy individuals.DesignThis is a systematic review and meta-analysis.Data sourcesWe searched six databases for studies assessing the effects of MTr on motor function in healthy individuals, published between January 1995 and December 2018. The Cochrane risk of bias was used to assess the quality of the studies. A meta-analysis was conducted with narrative synthesis.Eligibility criteria for selecting studiesEnglish-language randomised controlled trials reporting the behavioural results in healthy individuals were included.ResultsFourteen randomised controlled trials involving 538 healthy individuals were eligible. Two short-term studies showed MTr was inferior to passive vision pattern (standardised mean difference 0.57 (95% CI 0.06 to 1.08), I2=0%, p=0.03). The methods varied and there is limited evidence supporting the effectiveness of MTr compared with three alternative training patterns, with insufficient evidence to support analyses of age, skill level or hand dominance.ConclusionThe limited evidence that MTr affects motor performance in healthy individuals is weak and inconsistent among studies. It is unclear whether the effects of MTr on motor performance are more pronounced than the direct vision pattern, passive vision pattern or action observation. Further studies are needed to explore the short-term and long-term benefits of MTr and its effects on motor learning in healthy individuals.PROSPERO registration numberCRD42019128881.
Family caregivers of advanced cancer patients: self-perceived competency and meaning-making
Authors: Teo Irene , Baid Drishti , Ozdemir Semra , Malhotra Chetna , Singh Ratna , Harding Richard , Malhotra Rahul , Yang Meijuan Grace , Neo Shirlyn Hui-Shan , Cheung Yin Bun , Neo Patricia Soek Hui , Kanesvaran Ravindran , Kumarakulasinghe Nesaretnam Barr , Lee Lai Heng , Koh Gerald Choon Huat , Finkelstein Eric A 
Published: December 2019

BackgroundFamily caregivers of patients with advanced cancer have been reported to provide long hours of care and be at risk for poor psychological outcomes. Although research has focused on the nature of caregiving burden, little attention has been paid to identifying protective factors that improve caregiver psychological outcomes.AimWe examined the relationship between caregivers’ time spent caregiving and the following psychological outcomes: anxiety, depression and caregiving esteem. Subsequently, we explored the main and moderating effects of caregiver-perceived self-competency and sense of meaning on caregiver psychological outcomes.Design/participantsCross-sectional analysis was conducted using the baseline data from an ongoing cohort study. Family caregivers of advanced cancer patients (n=287) were recruited from two tertiary hospitals in Singapore.ResultsTime spent caregiving was not significantly associated with caregiver anxiety, depression or caregiving esteem. However, significant main effects of self-competency on anxiety and caregiving esteem; and sense of meaning on anxiety, depression and caregiving esteem were observed. Moderator analyses further indicated that self-competency attenuated the positive relationship between time spent caregiving and anxiety, while sense of meaning attenuated the negative relationship between time spent caregiving and caregiving esteem.ConclusionGreater perceived self-competency and sense of meaning are related to better caregiver psychological outcomes, and protect caregivers from worsening outcomes as caregiving hours increase. Our findings suggest that screening caregivers for distress is an important part of care, and that supportive interventions for caregivers should aim to enhance their perceived caregiving competencies and the ability to make meaning of their caregiving role.
Murine Oviductal High-Grade Serous Carcinomas Mirror the Genomic Alterations, Gene Expression Profiles, and Immune Microenvironment of Their Human Counterparts
Authors: McCool Kevin W. , Freeman Zachary T. , Zhai Yali , Wu Rong , Hu Kevin , Liu Chia-Jen , Tomlins Scott A. , Fearon Eric R. , Magnuson Brian , Kuick Rork , Cho Kathleen R. 
Published: December 2019

AbstractRobust preclinical models of ovarian high-grade serous carcinoma (HGSC) are needed to advance our understanding of HGSC pathogenesis and to test novel strategies aimed at improving clinical outcomes for women with the disease. Genetically engineered mouse models of HGSC recapitulating the likely cell of origin (fallopian tube), underlying genetic defects, histology, and biologic behavior of human HGSCs have been developed. However, the degree to which the mouse tumors acquire the somatic genomic changes, gene expression profiles, and immune microenvironment that characterize human HGSCs remains unclear. We used integrated molecular characterization of oviductal HGSCs arising in the context of Brca1, Trp53, Rb1, and Nf1 (BPRN) inactivation to determine whether the mouse tumors recapitulate human HGSCs across multiple domains of molecular features. Targeted DNA sequencing showed the mouse BPRN tumors, but not endometrioid carcinoma-like tumors based on different genetic defects (e.g., Apc and Pten), acquire somatic mutations and widespread copy number alterations similar to those observed in human HGSCs. RNA sequencing showed the mouse HGSCs most closely resemble the so-called immunoreactive and mesenchymal subsets of human HGSCs. A combined immuno-genomic analysis demonstrated the immune microenvironment of BPRN tumors models key aspects of tumor-immune dynamics in the immunoreactive and mesenchymal subtypes of human HGSC, with enrichment of immunosuppressive cell subsets such as myeloid-derived suppressor cells and regulatory T cells. The findings further validate the BPRN model as a robust preclinical experimental platform to address current barriers to improved prevention, diagnosis, and treatment of this often lethal cancer.Significance:The acquired gene mutations, broad genomic alterations, and gene expression and immune cell–tumor axis changes in a mouse model of oviductal serous carcinoma closely mirror those of human tubo-ovarian high-grade serous carcinoma.
Tryptophan 2,3-Dioxygenase Expression Identified in Human Hepatocellular Carcinoma Cells and in Intratumoral Pericytes of Most Cancers
Authors: Hoffmann Delia , Dvorakova Tereza , Stroobant Vincent , Bouzin Caroline , Daumerie Aurélie , Solvay Marie , Klaessens Simon , Letellier Marie-Claire , Renauld Jean-Christophe , van Baren Nicolas , Lelotte Julie , Marbaix Etienne , Van den Eynde Benoit J. 
Published: December 2019

Abstract
Tryptophan catabolism is used by tumors to resist immune attack. It can be catalyzed by indoleamine 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO). IDO1 is frequently expressed in tumors and has been widely studied as a potential therapeutic target to reduce resistance to cancer immunotherapy. In contrast, TDO expression in tumors is not well characterized. Several human tumor cell lines constitutively express enzymatically active TDO. In human tumor samples, TDO expression has previously been detected by transcriptomics, but the lack of validated antibodies has precluded detection of the TDO protein and identification of TDO-expressing cells. Here, we developed novel TDO-specific monoclonal antibodies and confirmed by immunohistochemistry the expression of TDO in the majority of human cancers. In all hepatocarcinomas (10/10), TDO was expressed by most tumor cells. Some glioblastomas (10/39) and kidney carcinomas (1/10) also expressed TDO in tumor cells themselves but only in focal tumor areas. In addition, all cancers tested contained foci of nontumoral TDO-expressing cells, which were identified as pericytes by their expression of PDGFRβ and their location in vascular structures. These TDO-expressing pericytes belonged to morphologically abnormal tumor vessels and were found in high-grade tumors in the vicinity of necrotic or hemorrhagic areas, which were characterized by neoangiogenesis. We observed similar TDO-expressing pericytes in inflammatory pulmonary lesions containing granulation tissue, and in chorionic villi, two tissue types that also feature neoangiogenesis. Our results confirm TDO as a relevant immunotherapeutic target in hepatocellular carcinoma and suggest a proangiogenic role of TDO in other cancer types.
See article by Schramme et al., p. 32
МЕТОДИКА ОРГАНІЗАЦІЇ САМОСТІЙНОЇ РОБОТИ СТУДЕНТІВ НА ПРИКЛАДІ ДИСЦИПЛІНИ «МЕДИЧНА ТА БІОЛОГІЧНА ФІЗИКА» З ОГЛЯДУ НА МОЖЛИВОСТІ СИСТЕМИ ДИСТАНЦІЙНОГО НАВЧАННЯ EDX.ORG
Authors: Prokopchenko O. E. , Lukina H. M. , Ivanchenko O. Z. , Melnikova O. Z. , Prykhodko O. V. 
Published: December 2019

У статті визначено потенційні можливості платформи дистанційного навчання Еdx.org для організації і проведення самостійної роботи студентів при вивченні дисципліни «Медична та біологічна фізика» за напрямком підготовки магістра за спеціальністю «Лікувальна справа» (англомовна форма навчання).
Представлено результати порівняльного аналізу і виявлено спільні елементи навчальної програми з медичної та біологічної фізики й дистанційного курсу «Fundamentals of Neuroscience». Навчально-методичні матеріали від Edx.org ми розглядали як складову частину домашньої підготовки й основу для самостійної та аудиторної роботи студентів. Наведено приклад організації самостійної роботи студентів з використанням можливостей системи дистанційного навчання Edx.org. Легальне запозичення і використання окремих навчальних матеріалів для дистанційного навчання дозволяють актуалізувати, стандартизувати й оптимізувати роботу студентів при проведенні самостійної та індивідуальної роботи при вивченні дисципліни «Медична та біологічна фізика».
На основі проведеного аудиту курсу «Neuroscience» запропоновано використовувати організаційну структуру курсу з метою організації самостійної та аудиторної роботи студентів з дисципліни «Медична та біологічна фізика».
ЗАСВОЄННЯ СТУДЕНТАМИ ПРАКТИЧНИХ НАВИЧОК ПРИ ВИВЧЕННІ ПЕДІАТРІЇ
Authors: Sherbatyuk N. Y. , Horishnyi I. M. , Chornomudz I. B. 
Published: December 2019

У статті проаналізовано особливості засвоєння практичних навичок при вивченні педіатрії. Звертається увага на специфіку самого об’єкта пізнання – здорову та хвору дитину у різні вікові періоди. Запропонований алгоритм пізнання: «Знаю – розумію – бачив – робив – вмію». Підкреслена роль активної позиції студента в навчальному процесі. Студент, спостерігаючи за роботою викладача під час навчально-лікувального процесу, вчиться мистецтва спілкування з батьками хворої дитини та налагоджування контакту між лікарем та дитиною. Така практика дає можливість студенту втілювати складову алгоритму «бачив». В усіх нових навчальних програмах акцент робиться на самостійній роботі студента. Але ця складова навчального процесу буде ефективною для студента лише при умові достатнього багажу знань. Для цього доцільно проводити практичні заняття в клініці методами рольової гри чи дискусії малими групами. Приміряючи на себе роль лікаря, студент починає відчувати потребу в удосконаленні своїх знань, з’являється бажання до професійної самореалізації, самоосвіти та саморозвитку. Застосування вищенаведених особливостей дає можливість студенту краще оволодіти практичними навичками та допомагає скласти іспит ОСКІ, а також підготуватися до державного професійно орієнтованого іспиту на 6 курсі.
Causal Associations Between Serum Bilirubin Levels and Decreased Stroke Risk
Authors: Choi Yoonjeong , Lee Sun Ju , Spiller Wes , Jung Keum Ji , Lee Ji-Young , Kimm Heejin , Back Joung Hwan , Lee Sunmi , Jee Sun Ha 
Published: December 2019

Objective:
A number of epidemiological studies have reported that decreased serum bilirubin, an endogenous antioxidant, is associated with cardiovascular disease. However, previous Mendelian randomization analyses conducted using a single sample have shown no evidence of association.

Approach and Results:

A 2-sample summary Mendelian randomization study was performed by obtaining exposure and outcome data from separate nonoverlapping samples. We utilized data from the KoGES (Korean Genome and Epidemiology Study; n=25 406) and KCPS-II (Korean Cancer Prevention Study-II; n=14 541) biobank for serum bilirubin and stroke, respectively. Using KoGES, a total of 1784 single nucleotide polymorphisms associated with serum bilirubin levels were discovered using a genome-wide significance threshold (
P
<5×10
−8
), of which 10 single nucleotide polymorphisms were identified as independent (
R
2
<0.005) and adopted as genetic instruments. From KCPS-II, total and ischemic stroke cases were identified (n=1489 and n=686), with 12 366 acting as controls. Various 2-sample summary Mendelian randomization methods were employed, with Mendelian randomization estimates showing an inverse causal association between serum bilirubin levels and total stroke risk (odds ratio, 0.481 [95% CI, 0.234–0.988];
P
=0.046). This association increased in magnitude when restricting the analysis to ischemic stroke cases (odds ratio, 0.302 [95% CI, 0.105–0.868];
P
=0.026).

Conclusions:
Our findings provide evidence of significant causal relationship between high levels of bilirubin and decreased stroke risk in Korean population in agreement with observational approaches. This highlights the potential for bilirubin to serve as a therapeutic target for oxidative stress-related diseases such as stroke and suggests that previous findings were not a consequence of unmeasured confounding.
Netrin-1 and the Grade of Atherosclerosis Are Inversely Correlated in Humans
Authors: Bruikman Caroline S. , Vreeken Dianne , Hoogeveen Renate M. , Bom Michiel J. , Danad Ibrahim , Pinto-Sietsma Sara-Joan , van Zonneveld Anton Jan , Knaapen Paul , Hovingh G. Kees , Stroes Erik S.G. , van Gils Janine M. 
Published: December 2019

Objective:
Netrin-1 has been shown to play a role in the initiation of atherosclerosis in mice models. However, little is known about the role of Netrin-1 in humans. We set out to study whether Netrin-1 is associated with different stages of atherosclerosis.

Approach and Results:

Plasma Netrin-1 levels were measured in different patient cohorts: (1) 22 patients with high cardiovascular risk who underwent arterial wall inflammation assessment using positron-emission tomography / computed tomography, (2) 168 patients with a positive family history of premature atherosclerosis in whom coronary artery calcium scores were obtained, and (3) 104 patients with chest pain who underwent coronary computed tomography angiography imaging to evaluate plaque vulnerability and burden. Netrin-1 plasma levels were negatively correlated with arterial wall inflammation (β, −0.01 [95% CI, 0.02 to −0.01]
R
2
, 0.61;
P
<0.0001), and concentrations of Netrin-1 were significantly lower when atherosclerosis was present compared with individuals without atherosclerosis (28.01 versus 10.51 ng/mL,
P
<0.001). There was no difference in Netrin-1 plasma concentrations between patients with stable versus unstable plaques (11.17 versus 11.74 ng/mL,
P
=0.511). However, Netrin-1 plasma levels were negatively correlated to total plaque volume (β, −0.09 [95% CI, −0.11 to −0.08]
R
2
, 0.57,
P
<0.0001), calcified plaque volumes (β, −0.10 [95% CI, −0.12 to −0.08]
R
2
, 0.53;
P
<0.0001), and noncalcified plaque volumes (β, −0.08 [95% CI, −0.10 to −0.06]
R
2
, 0.41;
P
<0.0001). Treatment of inflammatory stimulated endothelial cells with plasma with high Netrin-1 level resulted in reduced endothelial inflammation and consequently, less monocyte adhesion.

ConclusionS:
Netrin-1 plasma levels are lower in patients with subclinical atherosclerosis and in patients with arterial wall inflammation. Netrin-1 is not associated with plaque vulnerability; however, it is negatively correlated to plaque burden, suggesting that Netrin-1 is involved in some, but not all, stages of atherosclerosis.
Low and Oscillatory Wall Shear Stress Is Not Related to Aortic Dilation in Patients With Bicuspid Aortic Valve
Authors: Dux-Santoy Lydia , Guala Andrea , Sotelo Julio , Uribe Sergio , Teixidó-Turà Gisela , Ruiz-Muñoz Aroa , Hurtado Daniel E. , Valente Filipa , Galian-Gay Laura , Gutiérrez Laura , González-Alujas Teresa , Johnson Kevin M. , Wieben Oliver , Ferreira-Gonzalez Ignacio , Evangelista Arturo , Rodríguez-Palomares José F. 
Published: December 2019

Objective:
To assess the relationship between regional wall shear stress (WSS) and oscillatory shear index (OSI) and aortic dilation in patients with bicuspid aortic valve (BAV).

Approach and Results:
Forty-six consecutive patients with BAV (63% with right-left-coronary-cusp fusion, aortic diameter ≤ 45 mm and no severe valvular disease) and 44 healthy volunteers were studied by time-resolved 3-dimensional phase-contrast magnetic resonance imaging. WSS and OSI were quantified at different levels of the ascending aorta and the aortic arch, and regional WSS and OSI maps were obtained. Seventy percent of BAV had ascending aorta dilation. Compared with healthy volunteers, patients with BAV had increased WSS and decreased OSI in most of the ascending aorta and the aortic arch. In both BAV and healthy volunteers, regions of high WSS matched regions of low OSI and vice versa. No regions of both low WSS and high OSI were identified in BAV compared with healthy volunteers. Patients with BAV with dilated compared with nondilated aorta presented low and oscillatory WSS in the aortic arch, but not in the ascending aorta where dilation is more prevalent. Furthermore, no regions of concomitant low WSS and high OSI were identified when BAV were compared according to leaflet fusion pattern, despite the well-known differences in regional dilation prevalence.

Conclusions:
Regions with low WSS and high OSI do not match those with the highest prevalence of dilation in patients with BAV, thus providing no evidence to support the low and oscillatory shear stress theory in the pathogenesis of proximal aorta dilation in the presence of BAV.
Changes in Convective Available Potential Energy and Convective Inhibition under Global Warming
Authors: Chen Jiao , Dai Aiguo , Zhang Yaocun , Rasmussen Kristen L. 
Published: December 2019

AbstractAtmospheric convective available potential energy (CAPE) is expected to increase under greenhouse gas–induced global warming, but a recent regional study also suggests enhanced convective inhibition (CIN) over land although its cause is not well understood. In this study, a global climate model is first evaluated by comparing its CAPE and CIN with reanalysis data, and then their future changes and the underlying causes are examined. The climate model reasonably captures the present-day CAPE and CIN patterns seen in the reanalysis, and projects increased CAPE almost everywhere and stronger CIN over most land under global warming. Over land, the cases or times with medium to strong CAPE or CIN would increase while cases with weak CAPE or CIN would decrease, leading to an overall strengthening in their mean values. These projected changes are confirmed by convection-permitting 4-km model simulations over the United States. The CAPE increase results mainly from increased low-level specific humidity, which leads to more latent heating and buoyancy for a lifted parcel above the level of free convection (LFC) and also a higher level of neutral buoyancy. The enhanced CIN over most land results mainly from reduced low-level relative humidity (RH), which leads to a higher lifting condensation level and a higher LFC and thus more negative buoyancy. Over tropical oceans, the near-surface RH increases slightly, leading to slight weakening of CIN. Over the subtropical eastern Pacific and Atlantic Ocean, the impact of reduced low-level atmospheric lapse rates overshadows the effect of increased specific humidity, leading to decreased CAPE.
Male Mortality Trends in the United States, 1900-2010: Progress, Challenges, and Opportunities
Authors: Jones Wanda K. , Hahn Robert A. , Parrish R. Gibson , Teutsch Steven M. , Chang Man-Huei 
Published: December 2019

Objectives: Male mortality fell substantially during the past century, and major causes of death changed. Building on our recent analysis of female mortality trends in the United States, we examined all-cause and cause-specific mortality trends at each decade from 1900 to 2010 among US males. Methods: We conducted a descriptive study of age-adjusted death rates (AADRs) for 11 categories of disease and injury stratified by race (white, nonwhite, and, when available, black), the excess of male mortality over female mortality ([male AADR − female AADR]/female AADR), and potential causes of persistent excess of male mortality. We used national mortality data for each decade. Results: From 1900 to 2010, the all-cause AADR declined 66.4% among white males and 74.5% among nonwhite males. Five major causes of death in 1900 were pneumonia and influenza, heart disease, stroke, tuberculosis, and unintentional nonmotor vehicle injuries; in 2010, infectious conditions were replaced by cancers and chronic lower respiratory diseases. The all-cause excess of male mortality rose from 9.1% in 1900 to 65.5% in 1980 among white males and a peak of 63.7% in 1990 among nonwhite males, subsequently falling among all groups. Conclusion: During the last century, AADRs among males declined more slowly than among females. Although the gap diminished in recent decades, exploration of social and behavioral factors may inform interventions that could further reduce death rates among males.