bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral brincidofovir decreases the incidence of HHV-6B viremia after allogeneic HCT
Authors: Hill Joshua A. , Nichols W. Garrett , Marty Francisco M. , Papanicolaou Genovefa A. , Brundage Thomas M. , Lanier Randall , Zerr Danielle M. , Boeckh Michael J. 
Published: February 2020

Abstract
Human herpesvirus 6B (HHV-6B) frequently reactivates after allogeneic hematopoietic cell transplantation (HCT). There are no randomized studies of antiviral treatments to prevent HHV-6B reactivation. Brincidofovir has high in vitro activity against HHV-6B and other DNA viruses, but its in vivo activity for HHV-6B has not been demonstrated. We performed a post hoc analysis of a randomized controlled trial of twice-weekly oral brincidofovir for cytomegalovirus prophylaxis after allogeneic HCT to study the effect of brincidofovir on HHV-6B reactivation. We included patients randomized within 2 weeks of HCT and who received at least 6 consecutive doses of study drug after randomization. We tested plasma for HHV-6B through week 6 post-HCT. The cohort consisted of 92 patients receiving brincidofovir and 61 receiving placebo. The cumulative incidence of HHV-6B plasma detection through day 42 post-HCT was significantly lower among patients receiving brincidofovir (14.2%) compared with placebo (32.4%; log-rank, 0.019). In an adjusted Cox model, brincidofovir exposure remained associated with a lower hazard for HHV-6B plasma detection (hazard ratio, 0.40; 95% confidence interval, 0.20-0.80). In conclusion, brincidofovir prophylaxis reduced HHV-6B reactivation after allogeneic HCT in a post hoc analysis of a randomized controlled trial. These data support the study of intravenous brincidofovir for HHV-6B prophylaxis.
Phosphorylated ERK1/2 in CD4 T cells is associated with acute GVHD in allogeneic hematopoietic stem cell transplantation
Authors: Itamura Hidekazu , Shindo Takero , Yoshioka Satoshi , Ishikawa Takayuki , Kimura Shinya 
Published: February 2020

Abstract
To diagnose graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is sometimes difficult. We showed previously that MEK inhibitors selectively suppress murine GVHD while retaining antiviral and antitumor immunity. Here, we asked whether the RAS/MEK/ERK pathway is activated in human allo-HSCT recipients with GVHD, and whether the phosphorylated ERK1/2 can be a biomarker of GVHD. Peripheral blood was sequentially collected from 20 allo-HSCT recipients: 1 bone marrow transplant, 7 peripheral blood stem cell transplants (PBSCT), and 12 cord blood transplants. Ten of the 20 allo-HSCT recipients developed GVHD, and phosphorylation of ERK1/2 in T and B cells was analyzed by flow cytometry. Occurrence of acute GVHD was associated with phosphorylation of ERK1/2 in CD4+ T cells at day 30 (P &lt; .001), which was suppressed by ex vivo exposure to a MEK inhibitor trametinib at clinically achievable concentrations. In particular, ERK1/2 was phosphorylated preferentially in naive/central memory CD4+ T cells. Notably, phosphorylation of ERK1/2 fell as GVHD improved. These results suggest that phosphorylation status of ERK1/2 in peripheral blood CD4+ T cells may be a future biomarker for diagnosing human GVHD, and the potential efficacy of MEK inhibitors against human GVHD.
A 4-gene leukemic stem cell score can independently predict the prognosis of myelodysplastic syndrome patients
Authors: Wang Yu-Hung , Lin Chien-Chin , Yao Chi-Yuan , Hsu Chia-Lang , Hou Hsin-An , Tsai Cheng-Hong , Chou Wen-Chien , Tien Hwei-Fang 
Published: February 2020

Abstract
Myelodysplastic syndrome (MDS) comprised a heterogeneous group of diseases. The prognosis of patients varies even in the same risk groups. Searching for novel prognostic markers is warranted. Leukemic stem cells (LSCs) are responsible for chemoresistance and relapse in leukemia. Recently, expressions of 17 genes related to stemness of LSCs were found to be associated with prognosis in acute myeloid leukemia patients. However, the clinical impact of LSC genes expressions in MDS, a disorder arising from hematopoietic stem cells, remains unclear. We analyzed expression profile of the 17 stemness-related genes in primary MDS patients and identified expression of 4 genes (LAPTM4B, NGFRAP1, EMP1, and CPXM1) were significantly correlated with overall survival (OS). We constructed an LSC4 scoring system based on the weighted sums of the expression of 4 genes and explored its clinical implications in MDS patients. Higher LSC4 scores were associated with higher revised International Prognostic Scoring System (IPSS-R) scores, complex cytogenetics, and mutations in RUNX1, ASXL1, and TP53. High-score patients had significantly shorter OS and leukemia-free survival (LFS), which was also confirmed in 2 independent validation cohorts. Subgroup analysis revealed the prognostic significance of LSC4 scores for OS remained valid across IPSS-R lower- and higher-risk groups. Furthermore, higher LSC4 score was an independent adverse risk factor for OS and LFS in multivariate analysis. In summary, LSC4 score can independently predict prognosis in MDS patients irrespective of IPSS-R risks and may be used to guide the treatment of MDS patients, especially lower-risk group in whom usually only supportive treatment is given.
The Pleural Effusion And Symptom Evaluation (PLEASE) study of breathlessness in patients with a symptomatic pleural effusion
Authors: Muruganandan Sanjeevan , Azzopardi Maree , Thomas Rajesh , Fitzgerald Deirdre B. , Kuok Yi Jin , Cheah Hui Min , Read Catherine A. , Budgeon Charley A. , Eastwood Peter R. , Jenkins Susan , Singh Bhajan , Murray Kevin , Lee Y.C. Gary 
Published: February 2020

IntroductionPathophysiology changes associated with pleural effusion, its drainage and factors governing symptom response are poorly understood. Our objective was to determine: 1) the effect of pleural effusion (and its drainage) on cardiorespiratory, functional and diaphragmatic parameters; and 2) the proportion as well as characteristics of patients with breathlessness relief post-drainage.MethodsProspectively enrolled patients with symptomatic pleural effusions were assessed at both pre-therapeutic drainage and at 24–36 h post-therapeutic drainage.Results145 participants completed pre-drainage and post-drainage tests; 93% had effusions ≥25% of hemithorax. The median volume drained was 1.68 L. Breathlessness scores improved post-drainage (mean visual analogue scale (VAS) score by 28.0±24 mm; dyspnoea-12 (D12) score by 10.5±8.8; resting Borg score before 6-min walk test (6-MWT) by 0.6±1.7; all p<0.0001). The 6-min walk distance (6-MWD) increased by 29.7±73.5 m, p<0.0001. Improvements in vital signs and spirometry were modest (forced expiratory volume in 1 s (FEV1) by 0.22 L, 95% CI 0.18–0.27; forced vital capacity (FVC) by 0.30 L, 95% CI 0.24–0.37). The ipsilateral hemi-diaphragm was flattened/everted in 50% of participants pre-drainage and 48% of participants exhibited paradoxical or no diaphragmatic movement. Post-drainage, hemi-diaphragm shape and movement were normal in 94% and 73% of participants, respectively. Drainage provided meaningful breathlessness relief (VAS score improved ≥14 mm) in 73% of participants irrespective of whether the lung expanded (mean difference 0.14, 95% CI 10.02–0.29; p=0.13). Multivariate analyses found that breathlessness relief was associated with significant breathlessness pre-drainage (odds ratio (OR) 5.83 per standard deviation (sd) decrease), baseline abnormal/paralyzed/paradoxical diaphragm movement (OR 4.37), benign aetiology (OR 3.39), higher pleural pH (OR persdincrease 1.92) and higher serum albumin level (OR persdincrease 1.73).ConclusionsBreathlessness and exercise tolerance improved in most patients with only a small mean improvement in spirometry and no change in oxygenation. Breathlessness improvement was similar in participants with and without trapped lung. Abnormal hemi-diaphragm shape and movement were independently associated with relief of breathlessness post-drainage.
Phenotype and outcome of pulmonary arterial hypertension patients carrying aTBX4mutation
Authors: Thoré Pierre , Girerd Barbara , Jaïs Xavier , Savale Laurent , Ghigna Maria-Rosa , Eyries Mélanie , Levy Marilyne , Ovaert Caroline , Servettaz Amélie , Guillaumot Anne , Dauphin Claire , Chabanne Céline , Boiffard Emmanuel , Cottin Vincent , Perros Frédéric , Simonneau Gérald , Sitbon Olivier , Soubrier Florent , Bonnet Damien , Remy-Jardin Martine , Chaouat Ari , Humbert Marc , Montani David 
Published: February 2020

IntroductionTBX4mutation causes small patella syndrome (SPS) and/or pulmonary arterial hypertension (PAH). The characteristics and outcomes of PAH associated withTBX4mutations are largely unknown.MethodsWe report the clinical, functional, radiologic, histologic and haemodynamic characteristics and outcomes of heritable PAH patients carrying aTBX4mutation from the French pulmonary hypertension (PH) network.Results20 patients were identified in 17 families. They were characterised by a median age at diagnosis of 29 years (0–76 years) and a female to male ratio of three. Most of the patients (70%) were in New York Heart Association (NYHA) functional class III or IV with a severe haemodynamic impairment (median pulmonary vascular resistance (PVR) of 13.6 (6.2–41.8) Wood units). Skeletal signs of SPS were present in 80% of cases. Half of the patients had mild restrictive or obstructive limitation and diffusing capacity of the lung for carbon monoxide (DLCO) was decreased in all patients. High-resolution computed tomography (HRCT) showed bronchial abnormalities, peri-bronchial cysts, mosaic distribution and mediastinal lymphadenopathies. PAH therapy was associated with significant clinical improvement. At follow-up (median 76 months), two patients had died and two had undergone lung transplantation. One-year, three-year and five-year event-free survival rates were 100%, 94% and 83%, respectively. Histologic examination of explanted lungs revealed alveolar growth abnormalities, major pulmonary vascular remodelling similar to that observed in idiopathic pulmonary arterial hypertension (IPAH) and accumulation of cholesterol crystals within the lung parenchyma.ConclusionPAH due toTBX4mutations may occur with or without skeletal abnormalities across a broad age range from birth to late adulthood. PAH is usually severe and associated with bronchial and parenchymal abnormalities.
Effect of individualized PEEP titration guided by intratidal compliance profile analysis on regional ventilation assessed by electrical impedance tomography – a randomized controlled trial
Authors: Weber Jonas , Gutjahr Jan , Schmidt Johannes , Lozano-Zahonero Sara , Borgmann Silke , Schumann Stefan , Wirth Steffen 
Published: February 2020

Abstract
Background
The application of positive end-expiratory pressure (PEEP) may reduce dynamic strain during mechanical ventilation. Although numerous approaches for PEEP titration have been proposed, there is no accepted strategy for titrating optimal PEEP. By analyzing intratidal compliance profiles, PEEP may be individually titrated for patients.

Methods
After obtaining informed consent, 60 consecutive patients undergoing general anesthesia were randomly allocated to mechanical ventilation with PEEP 5 cmH2O (control group) or PEEP individually titrated, guided by an analysis of the intratidal compliance profile (intervention group). The primary endpoint was the frequency of each nonlinear intratidal compliance (CRS) profile of the respiratory system (horizontal, increasing, decreasing, and mixed). The secondary endpoints measured were respiratory mechanics, hemodynamic variables, and regional ventilation, which was assessed via electrical impedance tomography.

Results
The frequencies of the CRS profiles were comparable between the groups. Besides PEEP [control: 5.0 (0.0), intervention: 5.8 (1.1) cmH2O, p < 0.001], the respiratory and hemodynamic variables were comparable between the two groups. The compliance profile analysis showed no significant differences between the two groups. The loss of ventral and dorsal regional ventilation was higher in the control [ventral: 41.0 (16.3)%; dorsal: 25.9 (13.8)%] than in the intervention group [ventral: 29.3 (17.6)%; dorsal: 16.4 (12.7)%; p (ventral) = 0.039, p (dorsal) = 0.028].

Conclusions
Unfavorable compliance profiles indicating tidal derecruitment were found less often than in earlier studies. Individualized PEEP titration resulted in slightly higher PEEP. A slight global increase in aeration associated with this was indicated by regional gain and loss analysis. Differences in dorsal to ventral ventilation distribution were not found.

Trial registration
This clinical trial was registered at the German Register for Clinical Trials (DRKS00008924) on August 10, 2015.
Early prediction of acquiring acute kidney injury for older inpatients using most effective laboratory test results
Authors: Chen Yi-Shian , Chou Che-Yi , Chen Arbee L.P. 
Published: February 2020

AbstractBackgroundAcute Kidney Injury (AKI) is common among inpatients. Severe AKI increases all-cause mortality especially in critically ill patients. Older patients are more at risk of AKI because of the declined renal function, increased comorbidities, aggressive medical treatments, and nephrotoxic drugs. Early prediction of AKI for older inpatients is therefore crucial.MethodsWe use 80 different laboratory tests from the electronic health records and two types of representations for each laboratory test, that is, we consider 160 (laboratory test, type) pairs one by one to do the prediction. By proposing new similarity measures and employing the classification technique of the K nearest neighbors, we are able to identify the most effective (laboratory test, type) pairs for the prediction. Furthermore, in order to know how early and accurately can AKI be predicted to make our method clinically useful, we evaluate the prediction performance of up to 5 days prior to the AKI event.ResultsWe compare our method with two existing works and it shows our method outperforms the others. In addition, we implemented an existing method using our dataset, which also shows our method has a better performance. The most effective (laboratory test, type) pairs found for different prediction times are slightly different. However, Blood Urea Nitrogen (BUN) is found the most effective (laboratory test, type) pair for most prediction times.ConclusionOur study is first to consider the last value and the trend of the sequence for each laboratory test. In addition, we define the exclusion criteria to identify the inpatients who develop AKI during hospitalization and we set the length of the data collection window to ensure the laboratory data we collect is close to the AKI time. Furthermore, we individually select the most effective (laboratory test, type) pairs to do the prediction for different days of early prediction. In the future, we will extend this approach and develop a system for early prediction of major diseases to help better disease management for inpatients.
What about lay counselors’ experiences of task-shifting mental health interventions? Example from a family-based intervention in Kenya
Authors: Wall Jonathan T. , Kaiser Bonnie N. , Friis-Healy Elsa A. , Ayuku David , Puffer Eve S. 
Published: February 2020

Abstract
Background
A key focus of health systems strengthening in low- and middle-income countries is increasing reach and access through task-shifting. As such models become more common, it is critical to understand the experiences of lay providers because they are on the forefront for delivering care services. A greater understanding would improve lay provider support and help them provide high-quality care. This is especially the case for those providing mental health services, as providing psychological care may pose unique stressors. We sought to understand experiences of lay counselors, focusing on identity, motivation, self-efficacy, stress, and burnout. The goal was to understand how taking on a new provider role influences their lives beyond simply assuming a new task, which would in turn help identify actionable steps to improve interventions with task-shifting components.

Methods
Semi-structured interviews (n = 20) and focus group discussions (n = 3) were conducted with three lay counselor groups with varying levels of experience delivering a community-based family therapy intervention in Eldoret, Kenya. Thematic analysis was conducted, including intercoder reliability checks. A Stress Map was created to visualize stress profiles using free-listing and pile-sorting data collected during interviews and focus group discussions.

Results
Counselors described high intrinsic motivation to become counselors and high self-efficacy after training. They reported positive experiences in the counselor role, with new skills improving their counseling and personal lives. As challenges arose, including client engagement difficulties and balancing many responsibilities, stress and burnout increased, dampening motivation and self-efficacy. In response, counselors described coping strategies, including seeking peer and supervisor support, that restored their motivation to persevere. At case completion, they again experienced high self-efficacy and a desire to continue.

Conclusions
Findings informed suggestions for ways to incorporate support for lay providers into task-shifting interventions at initiation, during training, and throughout implementation. These include acknowledging and preparing counselors for challenges during training, increasing explicit attention to counselor stress in supervision, fostering peer support among lay providers, and ensuring a fair balance between workload and compensation. Improving and building an evidence base around practices for supporting lay providers will improve the effectiveness and sustainability of lay provider-delivered interventions.
Primary aldosteronism concurrent with subclinical Cushing’s syndrome: a case report and review of the literature
Authors:   the Chongqing Primary Aldosteronism Study (CONPASS) Group, Zhang Yingxiao , Tan Jianyu , Yang Qin , Du Zhipeng , Yang Shumin , He Wenwen , Song Ying , Hu Jinbo , Yang Yi , Li Qifu , Zhang Yao , He Yunfeng , Cheng Qingfeng 
Published: February 2020

Abstract
Background
The prevalence of primary aldosteronism concurrent with subclinical Cushing’s syndrome was higher than previously thought. Through analyzing a rare clinical case, we summarized the diagnosis and management of primary aldosteronism with subclinical Cushing’s syndrome.

Case presentation
A 54-year-old Chinese man of Han nationality was diagnosed as having primary aldosteronism with subclinical Cushing’s syndrome. An abdominal computed tomography scan revealed a mass in his left adrenal gland and a mass in his right adrenal gland. After finishing sequential adrenal venous sampling without adrenocorticotropic hormone, the result reminded us that the left and right nodules were responsible for hypercortisolism and aldosterone hypersecretion, respectively. Right and left adrenalectomy were performed successively. The pathological diagnosis was adrenocortical adenoma for both. Histological findings revealed that the right one had positive immunostaining for CYP11B2 and the left one had positive immunostaining for CYP11B1. The immunohistochemistry result helped us to confirm the diagnosis. Somatic KCNJ5 mutation (Leu168Arg) was found in the right tumor; there was no KCNJ5 mutation in the left adrenal tumor.

Conclusions
We suggest that patients with primary aldosteronism should have a low-dose overnight dexamethasone suppression test to screen for hypercortisolism. It can help avoid misdiagnoses and contribute to proper understanding of the adrenal vein sampling result. Making sure of the nidus of aldosterone and cortisol secretion is crucial for the therapy of patients with primary aldosteronism and subclinical Cushing’s syndrome.
Fracture saturation in paintings makes them less vulnerable to environmental variations in museums
Authors: Bratasz Łukasz , Akoglu Kiraz Goze , Kékicheff Patrick 
Published: February 2020

Abstract
Understanding paintings as physical systems is fundamental for advancing environmental specifications that would allow for effective management of museum environments in terms of reducing energy use and carbon emissions while maintaining high standards of collection care. The current environmental specifications were derived using the criterion of the crack initiation in undamaged, usually new, material. In reality, historical paintings exhibit complex crack patterns called craquelures. The present paper analyses painted wood which is among the category of cultural objects most vulnerable to relative humidity and temperature fluctuations and frequently found in museum collections of various kinds. Fracture toughness determined experimentally for the most brittle component of pictorial layer—the ground layer (gesso) is used as a ‘failure criterion’. Comparison of energy release rate—calculated for the model of the gesso laid on a wooden substrate using finite element analysis—with the structure toughness, allowed the fracture saturation expressed as the ratio of spacing between cracks S to gesso layer thickness t to be determined for various combinations of the gesso stiffness and geometries of structural flaws at which cracks initiate. For flat geometry of a panel painting and panel thickness of 40 mm, representing the worst-case, largest stresses in the gesso layer, the fracture saturation occurs when S/t is larger than 5, even if flaws in the gesso layer are present. The paper shows that the fracture saturation significantly changes vulnerability of paintings to climate variations—a panel painting with developed craquelure network is significantly less vulnerable to climate variations than an undamaged one.
Impact of petroleum and non-petroleum indices on financial development in Oman
Authors: Alshubiri Faris Nasif , Tawfik Omar Ikbal , Jamil Syed Ahsan 
Published: February 2020

AbstractThis study analyzes the impact of petroleum and non-petroleum indices on the financial development of the Sultanate of Oman from 1978 to 2017. To this end, it uses the petroleum proxy of oil rents (% of gross domestic product, GDP) and the non-petroleum proxy of industry (including construction) value added (% of GDP); agriculture, forestry, and fishing value added (% of GDP); and services value added (% of GDP) to determine the effect on financial development, measured by the amount of domestic credit extended to the private sector by banks (% of GDP). It applies an autoregressive distributed lag (ARDL) model. The long-term equation illustrates that the agriculture and industry GDPs have a negative and significant relationship with domestic credit in Oman. However, the oil and service sector GDPs promote financial development. The short-term equation illustrates that the oil, agricultural, and service sectors have positive and significant effects on domestic credit. The conclusion is that the economy of Oman is still in the first phase of economic diversification. Accordingly, the government should use oil revenues to develop various non-oil industrial sectors. This would enhance the country’s competitiveness in the global economy and positively contribute to improving the liquidity of the banking sector for stimulating credit at the macroeconomic level.