bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hemodynamic assessment of diastolic function for experimental models
Authors: Ogilvie Leslie M. , Edgett Brittany A. , Huber Jason S. , Platt Mathew J. , Eberl Hermann J. , Lutchmedial Sohrab , Brunt Keith R. , Simpson Jeremy A. 
Published: March 2020

Traditionally, the evaluation of cardiac function has focused on systolic function; however, there is a growing appreciation for the contribution of diastolic function to overall cardiac health. Given the emerging interest in evaluating diastolic function in all models of heart failure, there is a need for sensitivity, accuracy, and precision in the hemodynamic assessment of diastolic function. Hemodynamics measure cardiac pressures in vivo, offering a direct assessment of diastolic function. In this review, we summarize the underlying principles of diastolic function, dividing diastole into two phases: 1) relaxation and 2) filling. We identify parameters used to comprehensively evaluate diastolic function by hemodynamics, clarify how each parameter is obtained, and consider the advantages and limitations associated with each measure. We provide a summary of the sensitivity of each diastolic parameter to loading conditions. Furthermore, we discuss differences that can occur in the accuracy of diastolic and systolic indices when generated by automated software compared with custom software analysis and the magnitude each parameter is influenced during inspiration with healthy breathing and a mild breathing load, commonly expected in heart failure. Finally, we identify key variables to control (e.g., body temperature, anesthetic, sampling rate) when collecting hemodynamic data. This review provides fundamental knowledge for users to succeed in troubleshooting and guidelines for evaluating diastolic function by hemodynamics in experimental models of heart failure.Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/assessment-of-diastolic-function/ .
Marrow-Infiltrating Regulatory T Cells Correlate with the Presence of Dysfunctional CD4+PD-1+ Cells and Inferior Survival in Patients with Newly Diagnosed Multiple Myeloma
Authors: Alrasheed Nouf , Lee Lydia , Ghorani Ehsan , Henry Jake Y. , Conde Lucia , Chin Melody , Galas-Filipowicz Daria , Furness Andrew J.S. , Chavda Selina J. , Richards Huw , De-Silva Dunnya , Cohen Oliver C. , Patel Dominic , Brooks Anthony , Rodriguez-Justo Manuel , Pule Martin , Herrero Javier , Quezada Sergio A. , Yong Kwee L. 
Published: March 2020

Abstract

Purpose:
Immune dysregulation is described in multiple myeloma. While preclinical models suggest a role for altered T-cell immunity in disease progression, the contribution of immune dysfunction to clinical outcomes remains unclear. We aimed to characterize marrow-infiltrating T cells in newly diagnosed patients and explore associations with outcomes of first-line therapy.

Experimental Design:
We undertook detailed characterization of T cells from bone marrow (BM) samples, focusing on immune checkpoints and features of immune dysfunction, correlating with clinical features and progression-free survival.

Results:
We found that patients with multiple myeloma had greater abundance of BM regulatory T cells (Tregs) which, in turn, expressed higher levels of the activation marker CD25 compared with healthy donors. Patients with higher frequencies of Tregs had shorter PFS and a distinct Treg immune checkpoint profile (increased PD-1, LAG-3) compared with patients with lower frequencies of Tregs. Analysis of CD4 and CD8 effectors revealed that low CD4effector (CD4eff):Treg ratio and increased frequency of PD-1–expressing CD4eff cells were independent predictors of early relapse over and above conventional risk factors, such as genetic risk and depth of response. Ex vivo functional analysis and RNA sequencing revealed that CD4 and CD8 cells from patients with greater abundance of CD4effPD-1+ cells displayed transcriptional and secretory features of dysfunction.

Conclusions:
BM-infiltrating T-cell subsets, specifically Tregs and PD-1–expressing CD4 effectors, negatively influence clinical outcomes in newly diagnosed patients. Pending confirmation in larger cohorts and further mechanistic work, these immune parameters may inform new risk models, and present potential targets for immunotherapeutic strategies.
Cabozantinib Reverses Renal Cell Carcinoma–mediated Osteoblast Inhibition in Three-dimensional CocultureIn Vitroand Reduces Bone OsteolysisIn Vivo
Authors: Pan Tianhong , Martinez Mariane , Hubka Kelsea M. , Song Jian H. , Lin Song-Chang , Yu Guoyu , Lee Yu-Chen , Gallick Gary E. , Tu Shi-Ming , Harrington Daniel A. , Farach-Carson Mary C. , Lin Sue-Hwa , Satcher Robert L. 
Published: March 2020

AbstractRenal cell carcinoma bone metastases (RCCBM) are typically osteolytic. We previously showed that BIGH3 (beta Ig-h3/TGFBI), secreted by 786-O renal cell carcinoma, plays a role in osteolytic bone lesion in RCCBM through inhibition of osteoblast (OSB) differentiation. To study this interaction, we employed three-dimensional (3D) hydrogels to coculture bone-derived 786-O (Bo-786) renal cell carcinoma cells with MC3T3-E1 pre-OSBs. Culturing pre-OSBs in the 3D hydrogels preserved their ability to differentiate into mature OSB; however, this process was decreased when pre-OSBs were cocultured with Bo-786 cells. Knockdown of BIGH3 in Bo-786 cells recovered OSB differentiation. Furthermore, treatment with bone morphogenetic protein 4, which stimulates OSB differentiation, or cabozantinib (CBZ), which inhibits VEGFR1 and MET tyrosine kinase activities, also increased OSB differentiation in the coculture. CBZ also inhibited pre-osteoclast RAW264.7 cell differentiation. Using RCCBM mouse models, we showed that CBZ inhibited Bo-786 tumor growth in bone. CBZ treatment also increased bone volume and OSB number, and decreased osteoclast number and blood vessel density. When tested in SN12PM6 renal cell carcinoma cells that have been transduced to overexpress BIGH3, CBZ also inhibited SN12PM6 tumor growth in bone. These observations suggest that enhancing OSB differentiation could be one of the therapeutic strategies for treating RCCBM that exhibit OSB inhibition characteristics, and that this 3D coculture system is an effective tool for screening osteoanabolic agents for further in vivo studies.
Heart Transplantation in Muscular Dystrophy Patients
Authors: Wells Dennis , Rizwan Raheel , Jefferies John L. , Bryant Roosevelt , Ryan Thomas D. , Lorts Angela , Chin Clifford , Zafar Farhan , Morales David L. 
Published: March 2020

Background:
Cardiomyopathy is a common complication among muscular dystrophy (MD) patients and often results in advanced heart failure and premature death. In spite of this, there is hesitancy to consider heart transplantation (HTx). This study describes the HTx outcomes in patients with MD in the United States.

Methods and Results:

All HTx in the United Network for Organ Sharing database from October 1, 1987, to March 31, 2016, were identified. Two patient groups were created: MD cohort (n=81), and a cohort of all other cardiomyopathies, called cardiomyopathy-unmatched (n=41 317). Propensity score matching (ratio 1:2) was performed on transplant age, gender transplant year, renal function, and inotropic support at transplant to form a cardiomyopathy-matched cohort (n=162). Patient characteristics and posttransplant outcomes were compared. In the 81 patients with MD, Becker was the most common type (42%–52%). All the analyzed preoperative characteristics did not statistically differ between the MD and cardiomyopathy-matched cohorts except ventricular assist device use (16% versus 30%;
P
=0.017), ventilator support (0% versus 6%;
P
=0.031), and donor race mismatch (30% versus 55%;
P
<0.001). Median time on waitlist was not statistically different between the 2 groups (52 versus 59 days;
P
=0.12). Posttransplant survival of MD cohort was not statistically different compared with cardiomyopathy-matched cohort (
P
=0.18; hazard ratio [95% CI], 0.71 [0.42–1.18]) and was better than the cardiomyopathy-unmatched cohort (
P
=0.004; hazard ratio [95% CI], 0.53 [0.34–0.82]). Among the types of MD, no statistical difference was observed in posttransplant survival of Becker MD versus non-Becker MD (
P
=0.12; hazard ratio [95% CI], 2.17 [0.79–6.01]).

Conclusions:
Patients with MD undergoing HTx had similar long-term posttransplant survival compared with matched cardiomyopathy-related HTx recipients. HTx appears to be an effective treatment for a select group of muscular dystrophy patients with end-stage heart failure.
Systematic Theology and Biblical Theology—Part One
Authors: Allen Michael 
Published: March 2020

Abstract
Debates about the definitions of and relationship between systematic theology and biblical theology have become commonplace. Institutional and intellectual programs have taken sides and stood over against each other. Even within the relatively small world of confessional Reformed theology, the matter has garnered a good bit of attention and controversy. Matters have only grown more complex with the rise, more recently, of theological interpretation of scripture or theological exegesis, which may or may not overlap with both systematics and biblical theology. This essay seeks to reflect on perhaps the most influential proposals thus far and then to suggest a way forward. To that end, proposals by Geerhardus Vos, John Murray, and Richard Gaffin will be examined at length. In each case, their argument will be traced patiently, with observations and questions raised in a preliminary manner. Deeper analysis and a counterproposal will appear in a second essay.
“While We Were Yet Enemies”
Authors: Ziegler Philip G. 
Published: March 2020

Abstract
A distinctive contribution of Protestant dogmatics is its account of the interrelation of divine grace and human sin in which saving grace comes upon fallen, sinful humanity. What is most evangelically interesting and significant to Reformed faith is that God graciously acts precisely for creatures who are turned away from and pitched against divine goodness, against divine vocation, and against divine love. Thus, to ask and answer the question of ‘nature and grace’ as such is not yet to have set the question of grace in its most significant and telling register. In conversation with insights from the Didache, the apostle Paul, and early modern Reformed doctrines of sin, this essay argues that we do not win the measure of divine grace unless and until we meet it in connection with our godlessness and enmity, that is, in God’s saving confrontation with radical human sinfulness.
Printing Chinese Characters, Engraving Chinese Types: Wooden Chinese Movable Type at the Imprimerie Nationale (1715-1819)
Authors: Bussotti Michela , Landry-Deron Isabelle 
Published: March 2020

Abstract
The collection of Chinese wooden movable types is among the oldest treasures of the Imprimerie Nationale. The types were carved in Paris between 1715 and 1819, and they are a legacy of the first French attempts to master the expertise necessary to print Chinese alongside Western alphabetic scripts. This article, which is the result of research conducted at the Imprimerie Nationale, combined with a study of historical and literary sources from various periods kept at the Bibliothèque nationale de France and at Italian libraries, provides a description of the types’ physical characteristics and relates how they were created, designed, organized, engraved, employed, classified and stored.
Our research focuses on the attempts to include Chinese characters in publications in Western languages which were made in Europe and particularly in France from the beginning of the eighteenth century onwards. At a time when Europeans were beginning to expand their range of activities in Asia, printing in Asian scripts was a technical as well as a commercial, political and intellectual challenge. With no Chinese typographer to help, the French team modelled the types on characters found in a Chinese dictionary imported into France by missionaries, and at the beginning of the nineteenth century they published two dictionaries which included Chinese characters printed with wooden type.
Making a Canonical Work: a Cultural History of the Mustard Seed Garden Manual of Painting, 1679-1949
Authors: Zhang Gillian Yanzhuang 
Published: March 2020

Abstract
As the most widely-used painting manual in China, the Mustard Seed Garden Manual of Painting (Jieziyuan huazhuan 芥子園畫傳, hereafter Mustard Seed) has long been considered to have been a handbook for beginners. This article problematizes this relatively fixed notion by examining different editions of the manual and argues that the pedagogical function that most people take for granted is an anachronistic construction. In fact, the woodblock-printed Mustard Seed was regarded as an illegitimate painting manual in the mainstream art scene after its publication because it used woodblock printing to convey painting techniques. The canonization of the manual started in the late Qing (1862-1911), as a result of the availability of affordable lithographic editions. It soon became a primer for many would-be painters and gradually entered art schools in the Republican period (1912-1949), changing the traditional pedagogies of painting education. While highlighting the multivalent social functions of Mustard Seed, this paper will also show how changes in printing technique are connected to Mustard Seed’s canonization.
Strategy on the Wintry Sea: The Russo-British Submarine Flotilla in the Baltic, 1914–1918
Authors: Johnson Ian Ona 
Published: March 2020

From 1914 to 1917, in severe weather conditions on the icy Baltic Sea, Russian and British submariners contested control of the sea lanes with the German Imperial Navy. Their accomplishments were largely forgotten after the war’s end. However, the Russo-British Baltic Submarine Flotilla played an important role in the war at sea in the First World War. Most significantly, in 1915 the Flotilla wreaked havoc on German naval planning and nearly cut Germany’s critical iron ore imports from Sweden. The results would lead to a strategic crisis in the German Imperial Admiralty Staff and delay Germany’s attempt to break the British blockade until 1916. Here, the significance of the Russo-British Baltic Submarine Flotilla to the broader strategy of the First World War – and its later impact on strategy in the Second World War – is re-examined.
Topographic Form Drag on Tides and Low-Frequency Flow: Observations of Nonlinear Lee Waves over a Tall Submarine Ridge near Palau
Authors: Voet Gunnar , Alford Matthew H. , MacKinnon Jennifer A. , Nash Jonathan D. 
Published: March 2020

AbstractTowed shipboard and moored observations show internal gravity waves over a tall, supercritical submarine ridge that reaches to 1000 m below the ocean surface in the tropical western Pacific north of Palau. The lee-wave or topographic Froude number, Nh0/U0 (where N is the buoyancy frequency, h0 the ridge height, and U0 the farfield velocity), ranged between 25 and 140. The waves were generated by a superposition of tidal and low-frequency flows and thus had two distinct energy sources with combined amplitudes of up to 0.2 m s−1. Local breaking of the waves led to enhanced rates of dissipation of turbulent kinetic energy reaching above 10−6 W kg−1 in the lee of the ridge near topography. Turbulence observations showed a stark contrast between conditions at spring and neap tide. During spring tide, when the tidal flow dominated, turbulence was approximately equally distributed around both sides of the ridge. During neap tide, when the mean flow dominated over tidal oscillations, turbulence was mostly observed on the downstream side of the ridge relative to the mean flow. The drag exerted by the ridge on the flow, estimated to for individual ridge crossings, and the associated power loss, thus provide an energy sink both for the low-frequency ocean circulation and the tidal flow.
The Role of Local Orography on the Development of a Severe Rainfall Event over Western Peninsular Malaysia: A Case Study
Authors: Mohd Nor Mohd Fadzil Firdzaus , Holloway Christopher E. , Inness Peter M. 
Published: March 2020

AbstractSevere rainfall events are common in western Peninsular Malaysia. They are usually short and intense, and occasionally cause flash floods and landslides. Forecasting these local events is difficult and understanding the mechanisms of the rainfall events is vital for the advancement of tropical weather forecasting. This study investigates the mechanisms responsible for a local heavy rainfall event on 2 May 2012 that caused flash floods and landslides using both observations and simulations with the limited-area high-resolution Met Office Unified Model (MetUM). Results suggest that previous day rainfalls over Peninsular Malaysia and Sumatra Island influenced the development of overnight rainfall over the Strait of Malacca by low-level flow convergence. Afternoon convection over the Titiwangsa Mountains over Peninsular Malaysia then induced rainfall development and the combination of these two events influenced the development of severe convective storm over western Peninsular Malaysia. Additionally, anomalously strong low-level northwesterlies also contributed to this event. Sensitivity studies were carried out to investigate the influence of the local orography on this event. Flattened Peninsular Malaysia orography causes a lack of rainfall over the central part of Peninsular Malaysia and Sumatra Island and produces a weaker overnight rainfall over the Strait of Malacca. By removing Sumatra Island in the final experiment, the western and inland parts of Peninsular Malaysia would receive more rainfall, as this region is more influenced by the westerly wind from the Indian Ocean. These results suggest the importance of the interaction between landmasses, orography, low-level flow, and the diurnal cycle on the development of heavy rainfall events.
Quality of life, depression, and anxiety of patients undergoing hemodialysis: Significant role of acceptance of the illness
Authors: Marthoenis Marthoenis , Syukri Maimun , Abdullah Abdullah , Tandi Teuku M Reza , Putra Nadisyah , Laura Hasna , Setiawan Arie , Sofyan Hizir , Schouler-Ocak Meryam 
Published: March 2020

Objective Routine dialysis is stressful. It has the possibility of leading to depression and anxiety and also reducing patients’ quality of life. Despite these significant consequences, these comorbidities have been rarely studied among Indonesian patients. This study aims to examine the rate of depression, anxiety, and the role of acceptance of their illness on patients’ quality of life. Method A total of 213 patients undergoing hemodialysis in three general hospitals in Aceh, Indonesia, were included in the study. The presence of depression, anxiety, and the quality of life of each patient was assessed using the hospital anxiety and depression scale and WHO quality of life-BREF questionnaires. Results The prevalence of depression and anxiety was 46% and 30.5%, respectively. Depression was only associated with the presence of anxiety and the duration of hemodialysis. Anxiety was negatively associated with quality of life but positively associated with depression and the prescription of an anxiolytic. Overall quality of life was associated with age, body mass index, the presence of anxiety, and acceptance of the illness. Acceptance of the illness was also independently associated with almost every domain of patients’ quality of life. Conclusions The rates of depression and anxiety among patients undergoing hemodialysis in the current study setting are relatively similar to the rates in other settings. Patients’ acceptance of their illnesses is significantly associated with the occurrence of anxiety and quality of life. Therefore, health practitioners should help patients accept their illnesses and the administration of regular hemodialysis.
Burden, quality of life, anxiety, and depressive symptoms among caregivers of hemodialysis patients: The role of social support
Authors: Shukri Madihah , Mustofai Mohd Azman , Md Yasin Md Aris Safree , Tuan Hadi Tuan Sharipah 
Published: March 2020

Objective The purpose of this study was to determine how burden and quality of life predict anxiety and depressive symptoms among caregivers of hemodialysis patients. Social support was included in the model as a proposed moderator in the above relationships. Methods This cross-sectional study involved 340 caregivers of chronic kidney patients undergoing hemodialysis. The setting was in Terengganu, Malaysia. The caregivers completed the measures of caregiving burden, quality of life, social support, and symptoms of anxiety and depression. Results About 28.8% and 52.4% of caregivers showed clinically moderate levels of anxiety and depressive symptoms, respectively. Furthermore, 35.9% and 3.8% of them showed clinically high levels of anxiety and depressive symptoms, respectively. Analyses showed that general quality of life was a significant predictor of both anxiety and depressive symptoms. Burden and psychological domains of quality of life significantly predicted anxiety. In addition, a lack of social support was a determinant of depressive symptoms. Evidence suggested that social support moderated the burden–anxiety relationship. Specifically, caregivers with low levels of social support showed more elevated levels of anxiety symptoms when their burden was higher. Conclusion There is an urgent need for early detection to initiate prompt treatment in this population. The study provides some important insights into offering comprehensive intervention to help caregivers cope more effectively through the provision of sufficient social support to buffer the effects of caregiving burden and improve mental health.
Higher dose weekly fluoxetine in hemodialysis patients: A case series report
Authors: Kauffman Kelley M , Dolata Jacqueline , Figueroa Maria , Gunzler Douglas , Huml Anne , Pencak Julie , Sehgal Ashwini R , Sajatovic Martha 
Published: March 2020

Objective The antidepressant medication fluoxetine at 90 mg dosed weekly is as effective and safe as standard formulation fluoxetine 20 mg dosed daily in patients with major depressive disorder. Weekly fluoxetine has not been well studied in hemodialysis patients, and doses beyond 90 mg/week have not been described in this population. This case series, derived from a larger study on depression in hemodialysis patients, describes the use of weekly fluoxetine at dosages beyond 90 mg/week. Method Hemodialysis patients with depressive symptom severity scored ≥10 on the 9-item Patient Health Questionnaire and major depressive disorder confirmed with Mini International Neuropsychiatric Interview were initially prescribed daily fluoxetine for two weeks and then transitioned to weekly fluoxetine. Dosage titration was made at the discretion of the prescribing clinician. Fluoxetine was continued for a total of 12 weeks. Results Four women, aged 24 to 65 years, on hemodialysis for 1 to 18 years, were started on weekly fluoxetine that was increased over several weeks up to 180 mg. Side effects included restlessness, dry mouth, sedation, and lightheadedness. Two patients ultimately had their weekly fluoxetine decreased back to 90 mg. However, all four continued weekly fluoxetine as part of poststudy aftercare and no longer met diagnostic criteria for major depressive disorder, current episode. Conclusions Weekly fluoxetine at doses of 180 mg may be a reasonable treatment consideration for hemodialysis patients who have partial or insufficient antidepressant response. Side effects may limit tolerance of the 180 mg dose in some individuals. Future research should investigate longer term health outcomes of weekly fluoxetine in this population.