bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uterine epithelial expression of the tumor necrosis factor superfamily: a strategy for immune privilege during pregnancy in a true epitheliochorial placentation species
Authors: Yoo Inkyu , Kye Yoon Chul , Han Jisoo , Kim Minjeong , Lee Soohyung , Jung Wonchul , Hong Minsun , Park Tae Sub , Yun Cheol-Heui , Ka Hakhyun 
Published: January 2020

AbstractThe maternal immune system tolerates semi-allogeneic placental tissues during pregnancy. Fas ligand (FASLG) and tumor necrosis factor superfamily 10 (TNFSF10) are known to be components of maternal immune tolerance in humans and mice. However, the role of FASLG and TNFSF10 in the tolerance process has not been studied in pigs, which form a true epitheliochorial type placenta. Thus, the present study examined the expression and function of FASLG and TNFSF10 and their receptors at the maternal-conceptus interface in pigs. The endometrium and conceptus tissues expressed FASLG and TNFSF10 and their receptor mRNAs during pregnancy in a stage-specific manner. During pregnancy, FASLG and TNFSF10 proteins were localized predominantly to endometrial luminal epithelial cells with strong signals on Day 30 to term and on Day 15, respectively, and receptors for TNFSF10 were localized to some stromal cells. Interferon-γ (IFNG) increased the expression of TNFSF10 and FAS in endometrial tissues. Co-culture of porcine endometrial epithelial cells over-expressing TNFSF10 with peripheral blood mononuclear cells yielded increased apoptotic cell death of lymphocytes and myeloid cells. In addition, many apoptotic T cells were found in the endometrium on Day 15 of pregnancy. The present study demonstrated that FASLG and TNFSF10 were expressed at the maternal-conceptus interface and conceptus-derived IFNG increased endometrial epithelial TNFSF10, which, in turn, induced apoptotic cell death of immune cells. These results suggest that endometrial epithelial FASLG and TNFSF10 may be critical for the formation of micro-environmental immune privilege at the maternal-conceptus interface for the establishment and maintenance of pregnancy in pigs.
Baseline reward processing and ventrostriatal dopamine function are associated with pramipexole response in depression
Authors: Whitton Alexis E , Reinen Jenna M , Slifstein Mark , Ang Yuen-Siang , McGrath Patrick J , Iosifescu Dan V , Abi-Dargham Anissa , Pizzagalli Diego A , Schneier Franklin R 
Published: January 2020

Abstract
The efficacy of dopamine agonists in treating major depressive disorder has been hypothesized to stem from effects on ventrostriatal dopamine and reward function. However, an important question is whether dopamine agonists are most beneficial for patients with reward-based deficits. This study evaluated whether measures of reward processing and ventrostriatal dopamine function predicted response to the dopamine agonist, pramipexole (ClinicalTrials.gov Identifier: NCT02033369). Individuals with major depressive disorder (n = 26) and healthy controls (n = 26) (mean ± SD age = 26.5 ± 5.9; 50% female) first underwent assessments of reward learning behaviour and ventrostriatal prediction error signalling (measured using functional MRI). 11C-(+)-PHNO PET before and after oral amphetamine was used to assess ventrostriatal dopamine release. The depressed group then received open-label pramipexole treatment for 6 weeks (0.5 mg/day titrated to a maximum daily dose of 2.5 mg). Symptoms were assessed weekly, and reward learning was reassessed post-treatment. At baseline, relative to controls, the depressed group showed lower reward learning (P = 0.02), a trend towards blunted reward-related prediction error signals (P = 0.07), and a trend towards increased amphetamine-induced dopamine release (P = 0.07). Despite symptom improvements following pramipexole (Cohen’s d ranging from 0.51 to 2.16 across symptom subscales), reward learning did not change after treatment. At a group level, baseline reward learning (P = 0.001) and prediction error signalling (P = 0.004) were both associated with symptom improvement, albeit in a direction opposite to initial predictions: patients with stronger pretreatment reward learning and reward-related prediction error signalling improved most. Baseline D2/3 receptor availability (P = 0.02) and dopamine release (P = 0.05) also predicted improvements in clinical functioning, with lower D2/3 receptor availability and lower dopamine release predicting greater improvements. Although these findings await replication, they suggest that measures of reward-related mesolimbic dopamine function may hold promise for identifying depressed individuals likely to respond favourably to dopaminergic pharmacotherapy.
Non-Parametric Combined Reference Regions and Prediction of Clinical Risk
Authors: Malka Roy , Brugnara Carlo , Cialic Ron , Higgins John M 
Published: January 2020

Abstract

Background
Many clinical decisions depend on estimating patient risk of clinical outcomes by interpreting test results relative to reference intervals, but standard application of reference intervals suffers from two major limitations that reduce the accuracy of clinical decisions: (1) each test result is assessed separately relative to a univariate reference interval, ignoring the rich pathophysiologic information in multivariate relationships, and (2) reference intervals are intended to reflect a population’s biological characteristics and are not calibrated for outcome prediction.

Methods
We developed a combined reference region (CRR), derived CRRs for some pairs of complete blood count (CBC) indices (RBC, MCH, RDW, WBC, PLT), and assessed whether the CRR could enhance the univariate reference interval’s prediction of a general clinical outcome, 5-year mortality risk (MR).

Results
The CRR significantly improved MR estimation for 21/21 patient subsets defined by current univariate reference intervals. The CRR identified individuals with &gt;2-fold increase in MR in many cases and uniformly improved the accuracy for all five pairs of tests considered. Overall, the 95% CRR identified individuals with a &gt;7× increase in 5-year MR.

Conclusions
The CRR enhances the accuracy of the prediction of 5-year MR relative to current univariate reference intervals. The CRR generalizes to higher numbers of tests or biomarkers, as well as to clinical outcomes more specific than MR, and may provide a general way to use existing data to enhance the accuracy and precision of clinical decisions.
Mass Spectrometry for Identification, Monitoring, and Minimal Residual Disease Detection of M-Proteins
Authors: Zajec M , Langerhorst P , VanDuijn M M , Gloerich J , Russcher H , van Gool A J , Luider T M , Joosten I , de Rijke Y B , Jacobs J F M 
Published: January 2020

Abstract

Background
Monoclonal gammopathies (MGs) are plasma cell disorders defined by the clonal expansion of plasma cells, resulting in the characteristic excretion of a monoclonal immunoglobulin (M-protein). M-protein detection and quantification are integral parts of the diagnosis and monitoring of MGs. Novel treatment modalities impose new challenges on the traditional electrophoretic and immunochemical methods that are routinely used for M-protein diagnostics, such as interferences from therapeutic monoclonal antibodies and the need for increased analytical sensitivity to measure minimal residual disease.

Content
Mass spectrometry (MS) is ideally suited to accurate mass measurements or targeted measurement of unique clonotypic peptide fragments. Based on these features, MS-based methods allow for the analytically sensitive measurement of the patient-specific M-protein.

Summary
This review provides a comprehensive overview of the MS methods that have been developed recently to detect, characterize, and quantify M-proteins. The advantages and disadvantages of using these techniques in clinical practice and the impact they will have on the management of patients with MGs are discussed.
A machine learning cardiac magnetic resonance approach to extract disease features and automate pulmonary arterial hypertension diagnosis
Authors: Swift Andrew J , Lu Haiping , Uthoff Johanna , Garg Pankaj , Cogliano Marcella , Taylor Jonathan , Metherall Peter , Zhou Shuo , Johns Christopher S , Alabed Samer , Condliffe Robin A , Lawrie Allan , Wild Jim M , Kiely David G 
Published: January 2020

Abstract

Aims
Pulmonary arterial hypertension (PAH) is a progressive condition with high mortality. Quantitative cardiovascular magnetic resonance (CMR) imaging metrics in PAH target individual cardiac structures and have diagnostic and prognostic utility but are challenging to acquire. The primary aim of this study was to develop and test a tensor-based machine learning approach to holistically identify diagnostic features in PAH using CMR, and secondarily, visualize and interpret key discriminative features associated with PAH.

Methods and results
Consecutive treatment naive patients with PAH or no evidence of pulmonary hypertension (PH), undergoing CMR and right heart catheterization within 48 h, were identified from the ASPIRE registry. A tensor-based machine learning approach, multilinear subspace learning, was developed and the diagnostic accuracy of this approach was compared with standard CMR measurements. Two hundred and twenty patients were identified: 150 with PAH and 70 with no PH. The diagnostic accuracy of the approach was high as assessed by area under the curve at receiver operating characteristic analysis (P &lt; 0.001): 0.92 for PAH, slightly higher than standard CMR metrics. Moreover, establishing the diagnosis using the approach was less time-consuming, being achieved within 10 s. Learnt features were visualized in feature maps with correspondence to cardiac phases, confirming known and also identifying potentially new diagnostic features in PAH.

Conclusion
A tensor-based machine learning approach has been developed and applied to CMR. High diagnostic accuracy has been shown for PAH diagnosis and new learnt features were visualized with diagnostic potential.
Clinical feasibility and safety of transoesophageal motor-evoked potential monitoring
Authors: Shiiya Norihiko , Tsuda Kazumasa , Yamanaka Ken , Takahashi Daisuke , Washiyama Naoki , Yamashita Katsushi , Kando Yumi , Ohashi Yuko 
Published: January 2020

Abstract

OBJECTIVES
Canine experiments have shown that transoesophageal motor-evoked potential monitoring is feasible, safe and stable, with a quicker response to ischaemia and a better prognostic value than transcranial motor-evoked potentials. We aimed to elucidate whether or not these findings were clinically reproducible.

METHODS
A bipolar oesophageal electrode mounted on a large-diameter silicon tube and a train of 5 biphasic wave stimuli were used for transoesophageal stimulation. Results of 18 patients (median age 74.5 years, 13 males) were analysed.

RESULTS
There were no mortalities, spinal cord injuries or complications related with transoesophageal stimulation. Transcranial motor-evoked potential could not be monitored up to the end of surgery in 3 patients for unknown reasons, 2 of whom from the beginning. Transoesophageal motor-evoked potential became non-evocable after manipulation of a transoesophageal echo probe in 2 patients. Strenuous movement of the upper limbs during transoesophageal stimulation was observed in 3 patients. In 14 patients who successfully completed both monitoring methods up to the end of surgery (11 thoraco-abdominal and 3 descending aortic repair), the final results were judged as false positives in 6 by transcranial stimulation and in 1 by transoesophageal stimulation. The stimulation intensity was significantly lower and the upper limb amplitude was significantly higher by transoesophageal stimulation, while the lower limb amplitude was comparable.

CONCLUSIONS
Transoesophageal motor-evoked potential monitoring is clinically feasible and safe with a low false positive rate. A better electrode design is required to avoid its migration by transoesophageal echo manipulation. Further studies may be warranted.

Clinical registration number
UMIN000022320.
Impact of minimally invasive extracorporeal circulation on coagulation—a randomized trial
Authors: Modrau Ivy Susanne , Halle Debbie Richards , Nielsen Per Hostrup , Kimose Hans Henrik , Greisen Jacob Raben , Kremke Michael , Hvas Anne-Mette 
Published: January 2020

Abstract

OBJECTIVES
Minimally invasive extracorporeal circulation (MiECC) is suggested to have favourable impact on blood loss compared to conventional extracorporeal circulation. We aimed to compare the impact of both systems on coagulation.

METHODS
Randomized trial comparing endogenous thrombin-generating potential early after elective coronary surgery employing either MiECC group (n = 30) or conventional extracorporeal circulation group (n = 30). Secondary outcomes were in vivo thrombin generation, bleeding end points and haemodilution, as well as morbidity and mortality up to 30-day follow-up.

RESULTS
Compared to the conventional extracorporeal circulation group, the MiECC group showed (i) a trend towards a higher early postoperative endogenous thrombin-generating potential (P = 0.06), (ii) lower intraoperative levels of thrombin–antithrombin complex and prothrombin fragment 1 + 2 (P &lt; 0.001), (iii) less haemodilution early postoperatively as measured by haematocrit and weight gain, but without correlation to coagulation factors or bleeding end points. Moreover, half as many patients required postoperative blood transfusion in the MiECC group (17% vs 37%, P = 0.14), although postoperative blood loss did not differ between groups (P = 0.84). Thrombin–antithrombin complex levels (rs = 0.36, P = 0.005) and prothrombin fragment 1 + 2 (rs = 0.45, P &lt; 0.001), but not early postoperative endogenous thrombin-generating potential (rs = 0.05, P = 0.72), showed significant correlation to increased transfusion requirements. The MiECC group demonstrated significantly lower levels of creatine kinase-MB, lactate dehydrogenase and free haemoglobin indicating superior myocardial protection, less tissue damage and less haemolysis, respectively. Perioperative morbidity and 30-day mortality did not differ between groups.

CONCLUSIONS
Conventional but not MiECC is associated with significant intraoperative thrombin generation despite full heparinization. No correlation between coagulation factors or bleeding end points with the degree of haemodilution could be ascertained.

ClinicalTrials.gov identifier
NCT03216720.
Diagnostic yield of hypertrophic cardiomyopathy in first-degree relatives of decedents with idiopathic left ventricular hypertrophy
Authors: Finocchiaro Gherardo , Dhutia Harshil , Gray Belinda , Ensam Bode , Papatheodorou Stathis , Miles Chris , Malhotra Aneil , Fanton Zeph , Bulleros Paulo , Homfray Tessa , Witney Adam A , Bunce Nicholas , Anderson Lisa J , Ware James S , Sharma Rajan , Tome Maite , Behr Elijah R , Sheppard Mary N , Papadakis Michael , Sharma Sanjay 
Published: January 2020

Abstract

Aims
Idiopathic left ventricular hypertrophy (LVH) is defined as LVH in the absence of myocyte disarray or secondary causes. It is unclear whether idiopathic LVH represents the phenotypic spectrum of hypertrophic cardiomyopathy (HCM) or whether it is a unique disease entity. We aimed to ascertain the prevalence of HCM in first-degree relatives of decedents from sudden death with idiopathic LVH at autopsy. Decedents also underwent molecular autopsy to identify the presence of pathogenic variants in genes implicated in HCM.

Methods and results
Families of 46 decedents with idiopathic LVH (125 first-degree relatives) were investigated with electrocardiogram, echocardiogram exercise tolerance test, cardiovascular magnetic resonance imaging, 24-h Holter, and ajmaline provocation test. Next-generation sequencing molecular autopsy was performed in 14 (30%) cases. Decedents with idiopathic LVH were aged 33 ± 14 years and 40 (87%) were male. Fourteen families (30%) comprising 16 individuals were diagnosed with cardiac disease, including Brugada syndrome (n = 8), long QT syndrome (n = 3), cardiomyopathy (n = 2), and Wolff–Parkinson–White syndrome (n = 1). None of the family members were diagnosed with HCM. Molecular autopsy did not identify any pathogenic or likely pathogenic variants in genes encoding sarcomeric proteins. Two decedents had pathogenic variants associated with long QT syndrome, which were confirmed in relatives with the clinical phenotype. One decedent had a pathogenic variant associated with Danon disease in the absence of any histopathological findings of the condition or clinical phenotype in the family.

Conclusion
Idiopathic LVH appears to be a distinct disease entity from HCM and is associated with fatal arrhythmias in individuals with primary arrhythmia syndromes. Family screening in relatives of decedents with idiopathic LVH should be comprehensive and encompass the broader spectrum of inherited cardiac conditions, including channelopathies.
Energetic and Environmental Constraints on the Community Structure of Benthic Microbial Mats in Lake Fryxell, Antarctica
Authors: Dillon Megan L , Hawes Ian , Jungblut Anne D , Mackey Tyler J , Eisen Jonathan A , Doran Peter T , Sumner Dawn Y 
Published: January 2020

ABSTRACT
Ecological communities are regulated by the flow of energy through environments. Energy flow is typically limited by access to photosynthetically active radiation (PAR) and oxygen concentration (O2). The microbial mats growing on the bottom of Lake Fryxell, Antarctica, have well-defined environmental gradients in PAR and (O2). We analyzed the metagenomes of layers from these microbial mats to test the extent to which access to oxygen and light controls community structure. We found variation in the diversity and relative abundances of Archaea, Bacteria and Eukaryotes across three (O2) and PAR conditions: high (O2) and maximum PAR, variable (O2) with lower maximum PAR, and low (O2) and maximum PAR. We found distinct communities structured by the optimization of energy use on a millimeter-scale across these conditions. In mat layers where (O2) was saturated, PAR structured the community. In contrast, (O2) positively correlated with diversity and affected the distribution of dominant populations across the three habitats, suggesting that meter-scale diversity is structured by energy availability. Microbial communities changed across covarying gradients of PAR and (O2). The comprehensive metagenomic analysis suggests that the benthic microbial communities in Lake Fryxell are structured by energy flow across both meter- and millimeter-scales.
Functional Connectivity of the Supplementary Motor Network Is Associated with Fried’s Modified Frailty Score in Older Adults
Authors: Lammers Florian , Zacharias Norman , Borchers Friedrich , Mörgeli Rudolf , Spies Claudia Doris , Winterer Georg 
Published: January 2020

Abstract
Frailty is a geriatric syndrome defined by coexistence of unintentional weight loss, low physical reserve, or activity and is associated with adverse health events. Neuroimaging studies reported structural white matter changes in frail patients. In the current study, we hypothesized that clinical frailty is associated also with functional changes in motion-related cortical areas, that is, (pre-)supplementary motor areas (SMA, pre-SMA). We expected that observed functional changes are related to motor-cognitive test performance. We studied a clinical sample of 143 cognitively healthy patients ≥65 years presenting for elective surgery, enrolled in the BioCog prospective multicentric cohort study on postoperative cognitive disorders. Participants underwent preoperative resting-state functional magnetic resonance imaging, motor-cognitive testing, and assessment of Fried’s modified frailty criteria. We analyzed functional connectivity associations with frailty and motor-cognitive test performance. Clinically robust patients (N = 60) showed higher connectivity in the SMA network compared to frail (N = 13) and prefrail (N = 70) patients. No changes were found in the pre-SMA network. SMA connectivity correlated with motor speed (Trail-Making-Test A) and manual dexterity (Grooved Pegboard Test). Our results suggest that diminished functional connectivity of the SMA is an early correlate of functional decline in the older adults . The SMA may serve as a potential treatment target in frailty.
Predictors of Unmet Need Among Informal Caregivers
Authors: Campione Joanne R , Zebrak Katarzyna A 
Published: January 2020

Abstract

Objectives
This study investigates the relationship of caregiver demographics, caregiving intensity, caregiver support use, and aspects of the caregiving situation to a self-reported measure of unmet need among U.S. informal caregivers of older adults living at home with various conditions.

Methods
Response data from 1,558 caregiver participants interviewed by telephone during the December 2016 baseline period of the Outcome Evaluation of the National Family Caregiver Support Program were used. Caregivers who responded “Definitely No” to the question “Are you receiving all the help you need?” were classified as reporting unmet need. Logistic regression was used to find significant factors associated with unmet need among the full sample and among caregivers tiered by three levels of burden.

Results
Unmet need was reported by 22% of the caregivers. In a fully adjusted model, unmet need was predicted by higher levels of caregiving intensity, non-White race of the caregiver, and the caregiver not feeling appreciated by their care recipient. Other predictors associated with unmet need were no use of caregiver educational services, fewer respite hours, not living in a rural area, and caregiver having an education past high school.

Discussion
Caregivers who do not feel appreciated by their care recipient and non-White caregivers should be identified as potential targets for intervention to address unmet need, especially if they are also reporting higher levels of caregiver burden. Understanding the factors associated with self-reported unmet need can assist caregiver support programs in measuring and addressing the needs of informal caregivers to support their continued caregiving.
The Public Health Road Map to Respond to the Growing Dementia Crisis
Authors: Olivari Benjamin S , French Molly E , McGuire Lisa C 
Published: January 2020

Abstract
As the proportion of older adults in the United States is projected to increase dramatically in the coming decades, it is imperative that public health address and maintain the cognitive health of this growing population. More than 5 million Americans live with Alzheimer’s disease and related dementias (ADRD) today, and this number is projected to more than double by 2050. The public health community must be proactive in outlining the response to this growing crisis. Promoting cognitive decline risk reduction, early detection and diagnosis, and increasing the use and availability of timely data are critical components of this response. To prepare state, local, and tribal organizations, CDC and the Alzheimer’s Association have developed a series of Road Maps that chart the public health response to dementia. Since the initial Healthy Brain Initiative (HBI) Road Map release in 2007, the Road Map has undergone two new iterations, with the most recent version, The HBI’s State and Local Public Health Partnerships to Address Dementia: The 2018–2023 Road Map, released in late 2018. Over the past several years, significant advances were made in the science of risk reduction and early detection of ADRD. As a result, the public health response requires a life-course approach that focuses on reducing risk and identifying memory issues earlier to improve health outcomes. The most recent Road Map was revised to accommodate these strides in the science and to effect change at the policy, systems, and environment levels. The 2018–2023 Road Map identifies 25 actions that state and local public health agencies and their partners can implement to promote cognitive health and address cognitive impairment and the needs of caregivers. The actions are categorized into four traditional domains of public health, and the Road Map can help public health and its partners chart a course for a dementia-prepared future.