bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinicopathologic characterisation of myeloid neoplasms with concurrent spliceosome mutations and myeloproliferative-neoplasm-associated mutations
Authors: Liu Yen-Chun , Illar Gwendolyn M , Bailey Nathanael Glen
Published: March 2020

Aims

Spliceosome genes (SF3B1,SRSF2,U2AF1andZRSR2) are commonly mutated in myeloid neoplasms, particularly in myelodysplastic syndromes (MDS).JAK2,MPLandCALRmutations are associated with myeloproliferative neoplasms (MPN). AlthoughSF3B1and MPN-associated mutations frequently co-occur in the rare entity MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), myeloid neoplasms with concurrent spliceosome and MPN-associated mutations encompass many disease entities and are not well characterised.

Methods

Specimens from 2016 to 2019 with concurrent spliceosome and MPN-associated mutations were identified, and the clinicopathologic features were assessed.

Results

The 36 cases were divided into mutational categories based on their spliceosome mutation. At diagnosis, cases with concurrentU2AF1and MPN-associated mutations had lower leucocyte counts and platelet counts than did the other groups. Cases with mutantSRSF2were more likely to haveASXL1andIDH2mutations, whileU2AF1-mutated neoplasms were more likely to have an abnormal karyotype. The most commonSF3B1K700 andU2AF1S34 mutational hotspots were underrepresented in our cohort of myeloid neoplasms with concurrent spliceosome and MPN-associated mutations, asSF3B1andU2AF1mutations tended to involve other codons. Numerous WHO-defined disease entities were represented in each spliceosome gene category; although MDS/MPN-RS-T were only identified in the group withSF3B1mutations, they constituted only 1/4 of the neoplasms in the category.

Conclusions

Myeloid neoplasms with different mutant splicing factor and concurrent MPN-associated mutations demonstrate somewhat different clinical and pathologic features, but t he association between genotypes and phenotypes in these overlapping neoplasms is not straightforward.
Effect of Primary Pci on the Recovery of Atrioventricular Block in Inferior Stemi Patients with Late Presentation (>12 Hours): Insights from a Single Center 10-Year Experience
Authors: Fan Xiaojuan , Maharjan Prabindra , Liu Ping , Bai Ling
Published: March 2020

There is no definite reperfusion time for inferior ST-elevation myocardial infarction (STEMI) patients presenting later than 12 hours after symptom onset and complicated by newly-developed atrioventricular block (AVB). It is not clear whether the percutaneous coronary intervention (PCI) could facilitate the recovery of AVB in this patient group. We conducted a retrospective study including 52 consecutive inferior STEMI patients with presenting time >12 hours and new onset second or third-degree AVB on admission. All of them underwent PCI. The clinical characteristics, time to PCI and time to AVB improvement after symptom onset were studied. There were 42 males and the mean age was 61±10 years. Median presenting time from symptom onset was 36 hours (ranging 13-192 hours). Median time to PCI was 6.0 days (ranging 1-15 days) and median time of AVB improvement from symptom onset was 5.0 days (ranging 1-15 days). 24 patients got improvement of atrioventricular conduction before PCI procedure (defined as preoperative group) while 28 patients got improvement of atrioventricular conduction after PCI procedure (defined as postoperative group). In the postoperative group, there was a strong association between time to PCI and time to AVB improvement (R2=0.752, p=0.000). No adverse PCI procedure-related complications or death occurred and all the patients got complete AVB recovery at discharge. Early PCI is safe and should be recommended as the priority strategy for late presenting inferior STEMI patients when complicated by AVB. Successful reperfusion of the infarct-related artery is helpful to facilitate AVB recovery in this situation.
Performance of anti-CD19 chimeric antigen receptor T cells in genetically defined classes of chronic lymphocytic leukemia
Authors: Mancikova Veronika , Peschelova Helena , Kozlova Veronika , Ledererova Aneta , Ladungova Adriana , Verner Jan , Loja Tomas , Folber Frantisek , Mayer Jiri , Pospisilova Sarka , Smida Michal
Published: March 2020

Background

While achieving prolonged remissions in other B cell-derived malignancies, chimeric antigen receptor (CAR) T cells still underperform when injected into patients with chronic lymphocytic leukemia (CLL). We studied the influence of genetics on CLL response to anti-CD19 CAR T-cell therapy.

Methods

First, we studied 32 primary CLL samples composed of 26 immunoglobulin heavy-chain gene variable (IGHV)-unmutated (9ATM-mutated, 8TP53-mutated, and 9 without mutations inATM,TP53,NOTCH1orSF3B1) and 6IGHV-mutated samples without mutations in the above-mentioned genes. Then, we mimicked the leukemic microenvironment in the primary cells by ‘2S stimulation’ through interleukin-2 and nuclear factor kappa B. Finally, CRISPR/Cas9-generatedATM-knockout andTP53-knockout clones (four and seven, respectively) from CLL-derived cell lines MEC1 and HG3 were used. All these samples were exposed to CAR T cells. In vivo survival study in NSG mice using HG3 wild-type (WT),ATM-knockout orTP53-knockout cells was also performed.

Results

Primary unstimulated CLL cells were specifically eliminated after >24 hours of coculture with CAR T cells. ‘2S’ stimulated cells showed increased survival when exposed to CAR T cells compared with unstimulated ones, confirming the positive effect of this stimulation on CLL cells’ in vitro fitness. After 96 hours of coculture, there was no difference in survival among the genetic classes. Finally, CAR T cells were specifically activated in vitro in the presence of target knockout cell lines as shown by the production of interferon-γ when compared with control (CTRL) T cells (p=0.0020), but there was no difference in knockout cells’ survival. In vivo, CAR T cells prolonged the survival of mice injected with WT,TP53-knockout andATM-knockout HG3 tumor cells as compared with CTRL T cells (p=0.0485, 0.0204 and <0.0001, respectively). When compared withATM-knockout,TP53-knockout disease was associated with an earlier time of onset (p<0.0001), higher tumor burden (p=0.0002) and inefficient T-cell engraftment (p=0.0012).

Conclusions

While in vitro no differences in survival of CLL cells of various genetic backgrounds were observed, CAR T cells showed a different effectiveness at eradicating tumor cells in vivo depending on the driver mutation. Early disease onset, high-tumor burden and inefficient T-cell engraftment, associated withTP53-knockout tumors in our experimental setting, ultimately led to inferior performance of CAR T cells.
Clinical prognosis of FLAIR hyperintense arteries in ischaemic stroke patients: a systematic review and meta-analysis
Authors: Zhou Zien , Malavera Alejandra , Yoshimura Sohei , Delcourt Candice , Mair Grant , Al-Shahi Salman Rustam , Demchuk Andrew M , Wardlaw Joanna M , Lindley Richard I , Anderson Craig S
Published: March 2020

Objective

We performed a systematic review and meta-analysis to determine the association of fluid-attenuated inversion recovery (FLAIR) hyperintense arteries (FLAIR-HAs) on brain MRI and prognosis after acute ischaemic stroke (AIS).

Methods

We searched Medline, Embase and Cochrane Central Register of Controlled Trials for studies reporting clinical or imaging outcomes with presence of FLAIR-HAs after AIS. Two researchers independently assessed eligibility of retrieved studies and extracted data, including from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Outcomes were unfavourable functional outcome (primary, modified Rankin scale scores 3–6 or 2–6), death, intermediate clinical and imaging outcomes. We performed subgroup analyses by treatment or types of FLAIR-HAs defined by location (at proximal/distal middle cerebral artery (MCA), within/beyond diffusion-weighted imaging (DWI) lesion) or extent.

Results

We included 36 cohort studies (33 prospectively collected) involving 3577 patients. FLAIR-HAs were not associated with functional outcome overall (pooled risk ratio 0.87, 95% CI 0.71 to 1.06), but were significantly associated with better outcome in those receiving endovascular therapy (0.56, 95% CI 0.41 to 0.75). Contrary to FLAIR-HAs at proximal MCA or within DWI lesions, FLAIR-HAs beyond DWI lesions were associated with better outcome (0.67, 95% CI 0.57 to 0.79). FLAIR-HAs favoured recanalisation (1.21, 95% CI 1.06 to 1.38) with increased risk of intracerebral haemorrhage (2.07, 95% CI 1.37 to 3.13) and early neurological deterioration (1.93, 95% CI 1.30 to 2.85).

Conclusions

FLAIR-HAs were not associated with functional outcome overall but were associated with outcome after endovascular therapy for AIS. FLAIR-HAs were also associated with early recanalisation or haemorrhagic complications, and early neurologic deterioration.

PROSPERO registration number

CRD42019131168.
Real-world treatment patterns, healthcare resource utilisation and costs in patients with systemic lupus erythematosus treated with belimumab: a retrospective analysis of claims data in the USA
Authors: Bell Christopher F , Priest Julie , Stott-Miller Marni , Kan Hong , Amelio Justyna , Song Xue , Limone Brendan , Noxon Virginia , Costenbader Karen H
Published: March 2020

Objective

To examine the effects of belimumab initiation on healthcare resource utilisation (HCRU) and costs in SLE.

Methods

This retrospective observational cohort study used healthcare administrative claims data from the IBM MarketScan Commercial Claims and Encounters Database to identify patients with SLE billing codes who received ≥1 intravenous belimumab infusion between March 2011 and December 2015. The first belimumab administration was the ‘index date’. During the 6-month postindex period, nine belimumab infusions were recommended: three during the initiation period and six during the maintenance period. HCRU and cost data for inpatient admissions, emergency department visits, physician office visits, hospital-based outpatient visits, laboratory services, other outpatient services and outpatient pharmacy prescriptions were compared in the 6-month pre/postindex periods.

Results

Of the 1879 patients with SLE included, 43% received ≥3 intravenous initiation administrations. An average of 5.3 (SD: 2.4) of the nine recommended belimumab administrations were received within 6 months. In the 6-month preindex versus postindex periods, significant reductions were noted for inpatient hospitalisations (18% vs 9%, p<0.001; mean visits: 0.3 vs 0.14, p<0.001) and emergency department visits (40% vs 24%, p<0.001; mean visits; 3.53 vs 1.96, p<0.001). Mean total costs were higher in the 6-month postindex versus preindex period ($41 426 vs $29 270; p<0.001).

Conclusions

In this study of real-world intravenous belimumab for SLE, adherence to recommended infusion schedules was low. Outpatient healthcare and associated costs were higher in the 6 months after belimumab was initiated, although inpatient costs were lower. Reasons for non-adherence with belimumab and implications should be investigated.
Who maintains good health functioning? The contribution of social, work-related and behavioural factors to mental and physical health functioning trajectories in ageing employees
Authors: Lallukka Tea , Hiilamo Aapo , Pietiläinen Olli , Mänty Minna , Kouvonen Anne , Rahkonen Ossi
Published: March 2020

Objectives

The determinants of poor functioning and subsequent early exit from work are well established but very little is known about the positive determinants of maintaining good functioning among the ageing workforce. We investigated modifiable determinants of maintaining good mental and physical health functioning.

Methods

We used prospective survey data collected across four waves among the midlife employees of the City of Helsinki, Finland, 2000–2017 (n=3342). Health functioning was repeatedly measured using the Short Form 36 (SF-36) inventory. Trajectories of mental and physical health functioning were separately examined using group-based trajectory analysis. Multinomial logistic regression models were fitted to examine determinants of each trajectory.

Results

Four trajectory solutions for the developmental patterns in health functioning during the follow-up period were selected, with a slightly different shape of the first trajectory for mental and physical functioning: (1) continuously low (mental), low and decreasing (physical), (2) increasing, (3) decreasing and (4) continuously high functioning. After adjustments, the employees in the continuously high mental health functioning group were more likely to have optimal job demands, high job control, no sleep problems and no binge drinking behaviour. Employees in the continuously high physical functioning group had more likely low levels of physically strenuous work and hazardous working environment and no sleep problems and normal weight.

Conclusion

High job control, good sleep and avoiding binge drinking may help maintain good mental health functioning. Low levels of physical or environmental work exposures, good sleep and recommended healthy weight may support maintenance of good physical health functioning among ageing employees.
The role of community pharmacists and their position in the delivery of diabetes care: an update for medical professionals
Authors: Brewster Sarah , Holt Richard , Portlock Jane , Price Hermione
Published: March 2020

Pharmacists are the third largest group of healthcare professionals worldwide, but are underused in the delivery of diabetes care. The aim of this narrative was to describe how integration of community pharmacy services into existing healthcare models may improve diabetes care. Relevant literature exploring pharmacy-led interventions for diabetes were identified from a search of Medline, Embase and Cinahl online databases. This review highlights that community pharmacists are accessible, experts in medicine management, trusted by the public and able to achieve financial savings. They are poorly integrated into existing healthcare models, and commissioning arrangements can be poorly perceived by the public and those working in primary care. Community pharmacy interventions in type 2 diabetes have similar, if not greater effects compared to those delivered by other healthcare professionals. It was concluded that community pharmacy interventions in diabetes are feasible, acceptable and deliver improved health outcomes. Future work should build public recognition of pharmacists and improve communication between them and other healthcare professionals.
Iterative approach to journal club
Authors: Summey Rebekah Mynatt , Leonard Whitney , Schiele Kristan , Tristan Sigrid , Young Amy , Vinas Emily , Ferriss James Stuart
Published: March 2020

To identify, evaluate and refine a journal club (JC) format that increases faculty and resident engagement. An initial needs assessment followed by a trial of three JC formats: traditional single presenter, debate style and facilitated small group discussion was piloted over 6 months. Anonymous feedback was collected. The facilitated small group format was chosen. Narrative and quantitative feedback were collected from residents and faculty at 6-month intervals for the next 24 months. Changes to the format were made using feedback. Fourteen residents (n=20, 70%) and 10 faculty (n=20, 50%) completed baseline surveys. We initially observed low resident (8/14, 57%) interest in JCs. Additionally, 9/14 (64%) of residents and 1/15 (7%) of faculty reported low confidence presenting articles publicly. After implementation of the new JC format, resident reported enjoyment, on a scale of 1–5, improved from 3.6 to 4.4 (p<0.01). We observed improvement in resident confidence in the ability to critique a paper (2.7 to 4.1, p<0.01) and in confidence speaking in front of both peers (3.8 to 4.6, p<0.01) and faculty (3.0 to 3.8, p=0.04). Faculty confidence with literature critique decreased (from 4.2 to 3.8), but enjoyment remained stable (4.3 to 4.2). A facilitated small group JC format was preferred in our programme. We observed measurable improvements in both resident interest and confidence, as well as sustained faculty interest in JCs. We fostered an environment of inquiry and identified areas of continued professional development.
Primary lateral sclerosis: diagnosis and management
Authors: Turner Martin R , Talbot Kevin
Published: March 2020

Primary lateral sclerosis (PLS) is a rare neurodegenerative disorder at the upper motor neurone extreme of the spectrum of motor neurone disease. The diagnosis is clinical and based on the characteristic features of slowly progressive spasticity beginning in the lower limbs, or more rarely with spastic dysarthria, typically presenting around 50 years of age. The absence of lower motor neurone involvement is considered to be a defining feature, but confident distinction of PLS from upper motor neurone-predominant forms of amyotrophic lateral sclerosis may be difficult in the first few years. Corticobulbar involvement in PLS is frequently accompanied by emotionality. While there may be dysphagia, gastrostomy is rarely required to maintain nutrition. Cognitive dysfunction is recognised, though dementia is rarely a prominent management issue. PLS is not necessarily life shortening. Specialised multidisciplinary care is recommended. Increasing international research cooperation is required if the aspiration of dedicated therapeutic trials for PLS is to be achieved.
Energy conservation technique improves dyspnoea when patients with severe COPD climb stairs: a randomised crossover study
Authors: Prieur Guillaume , Combret Yann , Medrinal Clement , Arnol Nathalie , Bonnevie Tristan , Gravier Francis-Edouard , Quieffin Jean , Lamia Bouchra , Reychler Gregory , Borel Jean-Christian
Published: March 2020

In this randomised, crossover trial, 22 patients with severe chronic obstructive pulmonary disease climbed six flights of stairs (108 steps) twice, under two test conditions: (1) energy conservation technique (ECT): participants were asked to rest for at least 5 seconds every three steps and (2) control condition: participants climbed the stairs at their own pace. Significant lower dyspnoea (primary outcome), leg discomfort, minute ventilation and capillary blood lactate under the ECT condition were found, with no change in total task time.

Clinical trial registration

NCT03564028
Investigation of a unilateral pleural effusion: What CT scan coverage is optimal?
Authors: Syer Tom , Arnold David T , Patole Sonia , Harvey John , Medford Andrew , Maskell Nicholas A , Edey Anthony
Published: March 2020

The use of thoracic CT for patients presenting with a unilateral pleural effusion is well established. However, there is no consensus with regard to the inclusion of the entire abdomen and pelvis in the initial imaging protocol. In this prospective UK-based study, 249 patients presenting with a unilateral effusion had a CT thorax/abdomen/pelvis performed. The prevalence of malignancy on thoracic CT was 56% (140/249). Clinically significant findings below the diaphragm were identified in 59 patients (24%). Integrating this approach into standard practice allows more rapid identification of the primary malignancy, upstaging lesions or alternative sites for biopsy.
Acute exacerbations of chronic obstructive pulmonary disease: in search of diagnostic biomarkers and treatable traits
Authors: Mathioudakis Alexander G , Janssens Wim , Sivapalan Pradeesh , Singanayagam Aran , Dransfield Mark T , Jensen Jens-Ulrik Stæhr , Vestbo Jørgen
Published: March 2020

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with a significant mortality, health and economic burden. Their diagnosis, assessment and management remain suboptimal and unchanged for decades. Recent clinical and translational studies revealed that the significant heterogeneity in mechanisms and outcomes of exacerbations could be resolved by grouping them etiologically. This is anticipated to lead to a better understanding of the biological processes that underlie each type of exacerbation and to allow the introduction of precision medicine interventions that could improve outcomes. This review summarises novel data on the diagnosis, phenotyping, targeted treatment and prevention of COPD exacerbations.
Investigation of small- to large-strain moduli correlations of normally consolidated granular soils
Authors: Lashin Ibrahim , Ghali Michael , Hussien Mahmoud N. , Chekired Mohamed , Karray Mourad
Published: March 2020

The establishment of correlations between the small-strain shear modulus (Go) and other soil parameters (such as the oedometer constrained modulus, Moedo) at large deformations constitutes an important step toward more precise modeling of soil deformation behavior. In this study, the shear wave velocities (Vs) of 22 different granular soils of various physical characteristics were measured experimentally using the piezoelectric ring-actuator technique (P-RAT) incorporated in the conventional oedometer cell. For each sample tested, the development of Moedowith the development of relative density (Id), as well as the void ratio (e), was recorded. Then, the obtained Vsand Moedo/Gotrends were correlated to the physical parameters of the tested granular soils with the development of e and Id. A practical application employing the achievements in geotechnical engineering design was also evaluated. Based on the proposed correlations, geotechnical designers can easily estimate in situ stress–settlement behavior from the predicted Moedoand Idvalues using simple in situ measurements.
Evaluating heteroleptic copper(I)-based complexes bearing π-extended diimines in different photocatalytic processes
Authors: Sosoe Johann , Cruché Corentin , Morin Émilie , Collins Shawn K.
Published: March 2020

A series of 12 new copper-based photocatalysts of the type Cu(N^N)(P^P)BF4 were synthesized bearing π-extended diimine ligands. The complexes have red shifted absorptions and larger extinction coefficients than complexes prepared with a parent diimine, dmp. The complexes were evaluated for their ability to promote three different photochemical transformations. Although the complexes were inactive in a reductive PCET process, the complexes afforded good yields in both SET and ET processes. Interestingly, homoleptic copper-complexes derived from the π-extended diimines were significantly more active in SET processes than analogous complexes with simpler diimines.
Counting metastable states of Ising spin glasses on hypercubic lattices
Authors: Schnabel Stefan , Janke Wolfhard
Published: March 2020

We describe how metastable states of Ising spin glasses can be counted by means of Monte Carlo computer simulations. The method is applied to systems defined on hypercubic lattices in one to six dimensions with up to about 103 spins. It is shown that the number of metastable states obtained for different disorder realizations satisfies a log-normal distribution. We investigate the distribution of energies of metastable states by means of moments and cumulants.

Graphical abstract
Quantification of quantumness in neutrino oscillations
Authors: Ming Fei , Song Xue-Ke , Ling Jiajie , Ye Liu , Wang Dong
Published: March 2020

Neutrino oscillation is an important physical phenomenon in elementary particle physics, and its nonclassical features can be revealed by the Leggett–Garg inequality. It shows that its quantum coherence can be sustained over astrophysical length scales. In this work, we investigate the measure of quantumness in experimentally observed neutrino oscillations via the nonlocal advantage of quantum coherence (NAQC), quantum steering, and Bell nonlocality. From various neutrino sources, ensembles of reactor and accelerator neutrinos are analyzed at distinct energies, such as Daya Bay (0.5  km and 1.6 km) and MINOS (735 km) collaborations. The NAQC of two-flavor neutrino oscillation is characterized experimentally compared to the theoretical prediction. It exhibits non-monotonously evolutive phenomenon with the increase of energy. Furthermore, it is found that the NAQC is a stronger quantum correlation than quantum steering and Bell nonlocality even in the order of km. Hence, for an arbitrary bipartite neutrino-flavor state with achieving a NAQC, it must be also a steerable and Bell nonlocal state. The results might offer an insight into the neutrino oscillation for the further applications on quantum information processing.
Minimal vectorlike model in supersymmetric unification
Authors: Zheng Sibo
Published: March 2020

Compared to the minimal supersymmetric standard model, an extension by vectorlike fermions is able to explain the Higgs mass while retains the grand unification. We investigate the minimal vectorlike model by focusing on the vectorlike electroweak sector. We firstly derive the mass spectrum in the electroweak sector, then calculate the one-loop effects on the Higgs physics, and finally explore either vectorlike or neutralino dark matter. Collider constraints are briefly discussed.
Exclusion inside or at the border of conformal bootstrap continent
Authors: Nakayama Yu
Published: March 2020

How large can anomalous dimensions be in conformal field theories? What can we do to attain larger values? One attempt to obtain large anomalous dimensions efficiently is to use the Pauli exclusion principle. Certain operators constructed out of constituent fermions cannot form bound states without introducing nontrivial excitations. To assess the efficiency of this mechanism, we compare them with the numerical conformal bootstrap bound as well as with other interacting field theory examples. In two dimensions, it turns out to be the most efficient: it saturates the bound and is located at the (second) kink. In higher dimensions, it more or less saturates the bound but it may be slightly inside.
Network Resilience Assessment via QoS Degradation Metrics
Authors: Nguyen Lan N. , Thai My T.
Published: March 2020

This paper focuses on network resilience to perturbation of edge weight. Other than connectivity, many network applications nowadays rely upon some measure of network distance between a pair of connected nodes. In these systems, a metric related to network functionality is associated to each edge. A pair of nodes only being functional if the weighted, shortest-path distance between the pair is below a given threshold T. Consequently, a natural question is on which degree the change of edge weights can damage the network functionality? With this motivation, we study a new problem, Quality of Service Degradation : given a set of pairs, find a minimum budget to increase the edge weights which ensures the distance between each pair exceeds T . We introduce four algorithms with theoretical performance guarantees for this problem. Each of them has its own strength in trade-off between effectiveness and running time, which are illustrated both in theory and comprehensive experimental evaluation.
TeksDB
Authors: Han Youil , Kim Bryan S. , Yeon Jeseong , Lee Sungjin , Lee Eunji
Published: March 2020

In this paper, we examine the design tradeoffs of existing in-memory data structures of a state-of-the-art key-value store. We observe that no data structures provide both fast point-accesses and consistent ranged- retrievals, and naive amalgamations of existing structures fail to get the best of both worlds. Furthermore, our experiments reveal a performance anomaly when increasing the memory size: as more key-value pairs are maintained in memory, the shortcomings of the data structures exacerbate. To address the above problems, we present TeksDB, a fast and consistent key-value store with a novel in-memory data structure, which effciently handles both point- and ranged- accesses at a modest increase in memory footprint. Our evaluation demonstrates that TeksDB outperforms RocksDB by 3.6×, 9×, and 4.5× for get, scan, and range_query, respectively. The effectiveness of TeksDB extends to real-world workloads, achieving up to 3.3× speedup for YCSB.
Crystal Gazer
Authors: Akram Shoaib , Sartor Jennifer , McKinley Kathryn , Eeckhout Lieven
Published: March 2020

Non-volatile memories (NVM) offer greater capacity than DRAM but suffer from high latency and low write endurance. Hybrid memories combine DRAM and NVM to form scalable memory systems with the promise of high capacity, low energy consumption, and high endurance. Automatically managing hybrid NVM-DRAM memories to achieve their promise without changing user applications or their programming models remains an open question. This paper uses garbage collection in managed languages to exploit NVM capacity while preventing NVM wear out in hybrid memories with no changes to the programming model. We introduce profile-driven write-rationing garbage collection. Allocation sites that produce frequently written objects are predicted based on previous program executions. Objects are initially allocated in a DRAM nursery space. The collector copies surviving nursery objects from highly written sites to a mature DRAM space and read-mostly objects to a mature NVM space.Write-intensity prediction for 15 Java benchmarks accurately places objects in the correct space, eliminating expensive object monitoring from prior write-rationing garbage collectors. Furthermore, our technique exposes a Pareto tradeoff between DRAM usage and NVM lifetime, unlike prior work. Experimental results on NUMA hardware that emulates hybrid NVM-DRAM memory demonstrates that profile-driven write-rationing garbage collection reduces the number of writes to NVM compared to prior work to extend its lifetime, maximizes the use of NVM for its capacity, and achieves good performance.
Competitive Online Optimization under Inventory Constraints
Authors: Lin Qiulin , Yi Hanling , Pang John , Chen Minghua , Wierman Adam , Honig Michael , Xiao Yuanzhang
Published: March 2020

This paper studies online optimization under inventory (budget) constraints. While online optimization is a well-studied topic, versions with inventory constraints have proven difficult. We consider a formulation of inventory-constrained optimization that is a generalization of the classic one-way trading problem and has a wide range of applications. We present a new algorithmic framework, \textsfCR-Pursuit, and prove that it achieves the minimal competitive ratio among all deterministic algorithms (up to a problem-dependent constant factor) for inventory-constrained online optimization. Our algorithm and its analysis not only simplify and unify the state-of-the-art results for the standard one-way trading problem, but they also establish novel bounds for generalizations including concave revenue functions. For example, for one-way trading with price elasticity, the \textsfCR-Pursuit algorithm achieves a competitive ratio that is within a small additive constant (i.e., 1/3) to the lower bound of ln 0+1, where 0 is the ratio between the maximum and minimum base prices.
Ethics of Conducting Clinical Research in an Outbreak Setting
Authors: Edwards Kathryn M. , Kochhar Sonali
Published: March 2020

The conduct of clinical trials during the West Africa Ebola outbreak in 2014 highlighted many ethical challenges. How these challenges were addressed, what clinical studies were conducted during that outbreak, and the lessons learned for dealing with future outbreaks were the subject of a National Academy of Medicine committee report titled Integrating Clinical Research into Epidemic Response: The Ebola Experience. This report suggested improvements for research during subsequent emerging or re-emerging outbreaks and is summarized in this review. We also discuss the current Ebola outbreak in the Democratic Republic of the Congo and highlight how the dialogue has changed and how successful clinical trials have been implemented. We conclude with a description of productive efforts to include pregnant women and children in therapeutic and vaccine trials during outbreaks that are currently ongoing.
A Four-Layers Hamburger-Structure PVDF-HFP/Al2O3/PE/PVDF-HFP Composite Separator for Pouch Lithium-Ion Batteries with Enhanced Safety and Reliability
Authors: Wang Zheng , Pang Peipei , Ma Zhen , Chen Hongyu , Nan Junmin
Published: March 2020

A unique composite separator with four-layers hamburger-structure is prepared and demonstrated to be promising application in lithium-ion batteries (LIBs) with enhanced safety and reliability. Using polyolefin (PE) as substrate, Al2O3 as heat resistance layer, and 2 layers of polyvinylidene difluoride hexafluoropropylene (PVDF-HFP) on the upper and lower, this PVDF-HFP/Al2O3/PE/PVDF-HFP (PH/Al/PE/PH) separator is constructed through a gravure printing and phase transfer process. Compared with PE substrate coating with the mixture of Al2O3 and PVDF-HFP (PH-Al/PE) separator, the as-prepared separator can further enhance the safety performance of LIBs. In external short and nail tests, the maximum temperatures of LIBs with PH/Al/PE/PH separators (100 °C and 103 °C) are lower than LIBs with PH-Al/PE separators (132 °C and 115 °C). And after hot-box test, the voltage of former (4.13 V) is more stable than later (3.78 V). Meanwhile, compared with PE substrate coated by Al2O3 (Al/PE), the cycle performance of LIBs with PH/Al/PE/PH separator is significantly improved, and the deformation of LIBs is effectively controlled. Furthermore, the mechanism for the enhancement of safety and reliability of LIBs is elucidated. The results indicate that this separator exhibits promising prospects in the application of LIBs with enhanced safety and reliability.
Screening Children with a Family History of Central Congenital Hypoventilation Syndrome
Authors: Emanuel Hina , Rennie Kimberly , Macdonald Kelly , Yadav Aravind , Mosquera Ricardo A.
Published: March 2020

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder of an autonomic nervous disorder that affects breathing. It is characterized by respiratory insufficiency secondary to insensitivity to hypoxemia and hypercarbia, particularly during sleep leading to persistent apnea. We report four individuals across two generations harboring heterozygous 25 polyalanine repeats mutations (PARMs) in PHOX2B with a varying degree of phenotypic clinical manifestations. Two family members who reported to be “asymptomatic” were subsequently diagnosed with CCHS, based on genetic testing, obtained because of their family history. Genetic studies in the family including a mother and three offsprings revealed in-frame five amino acid PARMs of PHOX2B consistent with CCHS in addition to full clinical assessment. All affected individuals had evidence of hypercapnia on blood gas analysis with PCO2 in the range of 32–70 (mean; 61). Nocturnal polysomnogram revealed evidence of hypoventilation in two individuals (1 offspring and mother) with the end-tidal CO2 median of 54. Magnetic resonance imaging of brain revealed no abnormalities in the brain stem. There was no evidence of cor pulmonale on echocardiograms in all individuals. Neuropsychological testing was conducted on all four patients; two patients (mother and 1 offspring) had normal results, while the other two offspring exhibited some impairments on neuropsychological testing. This case series emphasizes the importance of screening first-degree relatives of individuals with confirmed CCHS to minimize complications associated with long-term ventilatory impairment. It also suggests that some patients with CCHS should undergo neuropsychological evaluations to assess for cognitive weaknesses secondary to their CCHS.
Effectiveness of Entropy Weight Method in Decision-Making
Authors: Zhu Yuxin , Tian Dazuo , Yan Feng
Published: March 2020

Entropy weight method (EWM) is a commonly used weighting method that measures value dispersion in decision-making. The greater the degree of dispersion, the greater the degree of differentiation, and more information can be derived. Meanwhile, higher weight should be given to the index, and vice versa. This study shows that the rationality of the EWM in decision-making is questionable. One example is water source site selection, which is generated by Monte Carlo Simulation. First, too many zero values result in the standardization result of the EWM being prone to distortion. Subsequently, this outcome will lead to immense index weight with low actual differentiation degree. Second, in multi-index decision-making involving classification, the classification degree can accurately reflect the information amount of the index. However, the EWM only considers the numerical discrimination degree of the index and ignores rank discrimination. These two shortcomings indicate that the EWM cannot correctly reflect the importance of the index weight, thus resulting in distorted decision-making results.
Study of Di-Muon Production Process in pp Collision in CMS Data from Symmetry Scaling Perspective
Authors: Bhaduri Susmita , Bhaduri Anirban , Ghosh Dipak
Published: March 2020

An extensive knowledge of the dynamics of the process of pp collision serves as input to exhaustive theoretical models of strong interaction. This knowledge is also a baseline for a system to decipher the dynamics of AA collisions at relativistic and ultrarelativistic energies. Recent availability of di-muon data has triggered a spate of interests in revisiting strong interaction process, the study of which in detail is extremely important for enhancement of our understanding of not only the theory of strong interaction but also possible physics scenarios beyond the standard model. Apart from conventional approaches to the study of the dynamics of particle production in high-energy collision the present authors proposed a new approach with successful application in context of symmetry scaling in AA collision data from (ALICE-Collaboration, 2014) in the work (Bhaduri, S. et al., 2019) and pp collision data at 8TeV from (CMS-collaboration, 2017) in the work (Bhaduri, S. et al., 2019) and also in other numerous works with different collision data. This different approach essentially analyses fluctuation pattern from the perspective of symmetry scaling or degree of self-similarity involved in the process. This was done with the help of multifractal scaling analysis and also multifractal cross-correlation analysis using the single variable of pseudorapidity values of di-muon data taken out from the primary dataset of RunA(2011) and RunB(2012) of the pp collision at 7 TeV and 8 TeV, respectively, from (CMS-collaboration, 2016, 2017). High degree of persistent long-range cross-correlations (MF-DXA) exist between pseudorapidity-value and its corresponding azimuthal-value for different rapidity ranges. The different values of scaling exponents (across rapidity ranges and energies) signify that there may be multiple processes other than those conjectured, involved in the underlying dynamics of the production process of oppositely charged di-muons resulting in different kinds of scaling. Otherwise, the scaling exponents at different degrees would have remained the same across the rapidity ranges and also for different energies.
Improving Deep Learning for Forecasting Accuracy in Financial Data
Authors: Lin Shih-Lin , Huang Hua-Wei
Published: March 2020

Financial forecasting is based on the use of past and present financial information to make the best prediction of the future financial situation, to avoid high-risk situations, and to increase benefits. Such forecasts are of interest to anyone who wants to know the state of possible finances in the future, including investors and decision-makers. However, the complex nature of financial data makes it difficult to get accurate forecasts. Artificial intelligence, which has been shown to be suitable for analyzing very complex problems, can be applied to financial forecasting. Financial data is both nonlinear and nonstationary, with broadband frequency features. In other words, there is a large range of fluctuation, meaning that predictions made only using long short-term memory (LSTM) are not enough to ensure accuracy. This study uses an LSTM model for analysis of financial data, followed by a comparison of the analytical results with the actual data to see which has a larger root-mean-square-error (RMSE). The proposed method combines deep learning with empirical mode decomposition (EMD) to understand and predict financial trends from financial data. The financial data for this study are from the Taiwan corporate social responsibility (CSR) index. First, the EMD method is used to transform the CSR index data into a limited number of intrinsic mode functions (IMF). The bandwidth of these IMFs becomes narrower, with regular cyclic, periodic, or seasonal components in the time domain. In other words, the range of fluctuation is small. LSTM is a good way to forecast cyclic or seasonal data. The forecast result is obtained by adding all the IMFs together. It has been verified in past studies that only the LSTM and LSTM combined with the EMD can be used. The analytical results show that smaller RMSEs can be obtained using the LSTM combined with EMD compared to real data.
PERK Overexpression‐Mediated Nrf2/HO‐1 Pathway Alleviates Hypoxia/Reoxygenation‐Induced Injury in Neonatal Murine Cardiomyocytes via Improving Endoplasmic Reticulum Stress
Authors: Wang Jichun , Lu Li , Chen Sisi , Xie Jing , Lu Shuai , Zhou Yanli , Jiang Hong
Published: March 2020

Reperfusion processes following acute myocardial infarction (AMI) have been reported to induce additional cardiomyocyte death, known as ischemia‐reperfusion (I/R) injury. Endoplasmic reticulum (ER) stress is reported to be involved in the development of I/R injury. There is evidence that PERK exerts beneficial roles in alleviating ER stress. Here, we investigated whether upregulation of PERK improved cardiomyocytes injury induced by I/R. Specific siRNAs or adenovirus vectors were incubated with isolated neonatal cardiomyocytes (NCMs) to regulate expression levels of target genes including PERK, Nrf2, and HO‐1. Afterwards, hypoxia and subsequent reoxygenation (H/R) administration was performed as the in vitro model of I/R injury. MTT assay showed that H/R intervention decreased the viability of cells, yet PERK overexpression increased the cellular proliferative rate. Moreover, the upregulation of Nrf2 or HO‐1 elevated the growth rate of cells, while gene silencing of Nrf2 or HO‐1 reduced the viability of NCMs treated with PERK‐rAAV9. In addition, we observed that the apoptotic index of cells with H/R stimulation was reduced when NCMs were pretreated with PERK‐rAAV9, Nrf2‐rAAV9, or HO‐1‐rAAV9. After cells were incubated with Nrf2‐siRNA or HO‐1‐siRNA, the upregulation of PERK had no roles in affecting the apoptosis rate of NCMs damaged by H/R. Then, our findings indicated that there was a level decrease of GRP78, CRT, CHOP, and Caspase‐12 in NCMs of the PERK‐rAAV9 group compared to that of the H/R group. Both Nrf2 overexpression and HO‐1 upregulation reduced the expression of ER stress‐related proapoptotic factors, yet the expression suppression of Nrf2 and HO‐1 increased levels of GRP78, CRT, CHOP, and Caspase‐12 in NCMs treated with PERK‐rAAV9. Taken together, our results suggested that the effects of PERK against H/R injury might be attributed to the upregulation of Nrf2/HO‐1 cascade, followed by the inhibition of ER stress‐related apoptotic pathway.
Correlation Coefficients for a Study with Repeated Measures
Authors: Shan Guogen , Zhang Hua , Jiang Tao
Published: March 2020

Repeated measures are increasingly collected in a study to investigate the trajectory of measures over time. One of the first research questions is to determine the correlation between two measures. The following five methods for correlation calculation are compared: (1) Pearson correlation; (2) correlation of subject means; (3) partial correlation for subject effect; (4) partial correlation for visit effect; and (5) a mixed model approach. Pearson correlation coefficient is traditionally used in a cross-sectional study. Pearson correlation is close to the correlations computed from mixed-effects models that consider the correlation structure, but Pearson correlation may not be theoretically appropriate in a repeated-measure study as it ignores the correlation of the outcomes from multiple visits within the same subject. We compare these methods with regard to the average of correlation and the mean squared error. In general, correlation under the mixed-effects model with the compound symmetric structure is recommended as its correlation is close to the nominal level with small mean square error.
Numerical Simulation and Experimental Study on Flow of Polymer Aqueous Solution in Porous Jet Nozzle
Authors: Wei Minghui , Wu Chenghuai , Zhou Yanxi
Published: March 2020

The addition of a polymer to the jet medium enhances its ability to break rock, and the structure of the nozzle plays a vital role in the full utilization of energy. In this paper, a self-propelled porous jet bit with a support plate is designed, which can prevent the drill bit from jamming due to the jet nozzle against the bottom of the well during the drilling process. And the structural design of the cone-converging nozzle is applied to the forward center nozzle. The polymer additive jet flow field and the pure water jet flow field were compared by numerical simulation and experimental investigation. The results show that the polymer additive jet has a longer isokinetic core, and the rock-breaking volume of the polymer additive jet is much larger than that of the pure water jet, and the optimal spray distance is increased. The forward central jet with the conical convergent nozzle structure has more efficient rock-breaking ability.
A Five-Genes-Based Prognostic Signature for Cervical Cancer Overall Survival Prediction
Authors: Zhao Menghuang , Huang Wenbin , Zou Shuangwei , Shen Qi , Zhu Xueqiong
Published: March 2020

Aims. This study is aimed at identifying a prognostic signature for cervical cancer. Main Methods. The gene expression data and clinical information of cervical cancer and normal cervical tissues were acquired from The Cancer Genome Atlas and from three datasets of the Gene Expression Omnibus database. DESeq2 and Limma were employed to screen differentially expressed genes (DEGs). The overlapping DEGs among all datasets were considered the final DEGs. Then, the functional enrichment analysis was performed. Moreover, the Cox proportional hazards regression was performed to establish a prognostic signature of the DEGs. The Kaplan-Meier analysis was applied to test the model. Relationships between gene expression and clinicopathological parameters in cervical cancer, including age, HPV status, histology, stage, and lymph node metastasis, were analysed by the chi-square test. The somatic mutations of these prognostic genes were assessed through cBioPortal. The robustness of the model was verified in another two independent validation cohorts. Key Findings. In total, 169 overlapping upregulated genes and 29 overlapping downregulated genes were identified in cervical cancer compared with normal cervical tissues. Functional enrichment analysis indicated that the DEGs were mainly enriched in DNA replication, the cell cycle, and the p53 signalling pathway. Finally, a 5-gene- (ITM2A, DSG2, SPP1, EFNA1, and MMP1) based prognostic signature was built. According to this model, each patient was given a prognostic-related risk value. The Kaplan-Meier analysis showed that a higher risk was related to worse overall survival in cervical cancer, with an area under the receiver operating characteristic curve of 0.811 for 15 years. The validity of this model in the prediction of cervical cancer outcome was verified in another two independent datasets. In addition, our study also found that the low expression of ITM2A was associated with cervical adenocarcinoma. Interestingly, DSG2 was associated with the HPV status of cervical cancer. Significance. Our study constructed a prognostic model in cervical cancer and discovered two novel genes, ITM2A and DSG2, associated with cervical carcinogenesis and survival.