bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilateral adrenal haematoma complicated by adrenal insufficiency in a patient treated with bevacizumab
Authors: Smolenschi Cristina , Tazdait Melodie , Kuhn Emanuelle , Boige Valerie
Published: February 2021

Bevacizumab (bev) significantly improves outcomes of patients with metastatic colorectal cancer (mCRC). However, the addition of bev to concurrent chemotherapy significantly increased the risk of haemorrhage. We describe the case of a patient with mCRC who presented with acute diffuse abdominal pain following four cycles of bev-containing systemic chemotherapy. A CT revealed the appearance of bilateral adrenal enlargement suggestive of acute adrenal haematoma. Blood test results showed a dramatic decrease in cortisol level and highly elevated Adrenocorticotropic Hormone (ACTH) level suggesting an adrenal insufficiency. After differential diagnosis, we hypothesised that bev may have contributed to the development of a bilateral adrenal haematoma complicated by adrenal insufficiency. Bev was immediately withdrawn and the patient was subsequently treated with hydrocortisone substitution with favourable outcome. This case highlights for the first time the possibility of adrenal bleeding with bev-containing chemotherapy.
Consultant-led triage of paediatric hospital referrals: a service evaluation
Authors: Hodgson Heather Sharon , Webb Nicholas , Diskin Lynn
Published: February 2021

Objective

We established a paediatric demand management (PDM) service in our paediatric department in 2017. The aim of this consultant-delivered service is to manage referrals more efficiently by providing active triage of all referrals, daily rapid access clinics and easily accessible advice for primary healthcare professionals. This study presents an evaluation of this service.

Design

Mixed-methods service evaluation with analysis of data for every contact with the PDM service over a 2-year period. For each patient, the method of contact, reason for contact, presenting complaint and triage outcome were recorded. Feedback from general practitioners (GPs) and patients was gathered.

Results

Data were analysed for 7162 patients. More than a quarter (2034; 28%) of all referrals were managed with advice only. Of the 4703 outpatient clinic referrals, 1285 (27%) were managed without a clinic appointment. More than half (54%) of the requests for paediatric assessment unit (PAU) admission were managed alternatively, typically with advice only or a rapid access clinic appointment. This has reversed the increasing trend of PAU admissions from primary care of preceding years. Financial analysis suggested the avoidance of these clinic appointments, and PAU admissions provided a substantial cost saving.

Conclusions

Our results indicate that the PDM service has succeeded in reducing unnecessary hospital attendances by managing patients more effectively and strengthening partnerships with primary care. The service has received overwhelmingly positive feedback from GPs. This service could be replicated in other Trusts and developed in the future to facilitate further management of paediatric cases in a primary care setting.
Risks of post-colonoscopic polypectomy bleeding and thromboembolism with warfarin and direct oral anticoagulants: a population-based analysis
Authors: Lau Louis HS , Guo Cosmos LT , Yip Terry CF , Mak Joyce WY , Wong Sunny H , Lam Kelvin LY , Wong Grace LH , Ng Siew C , Chan Francis KL
Published: February 2021

Background

There were limited data on the risk of post-polypectomy bleeding (PPB) in patients on direct oral anticoagulants (DOAC). We aimed to evaluate the PPB and thromboembolic risks among DOAC and warfarin users in a population-based cohort.

Methods

We performed a territory-wide retrospective cohort study involving patients in Hong Kong from 2012 to 2020. Patients who received an oral anticoagulant and had undergone colonoscopy with polypectomy were identified. Propensity-score models with inverse probability of treatment weighting were developed for the warfarin-DOAC and between-DOAC comparisons. The primary outcome was clinically significant delayed PPB, defined as repeat colonoscopy requiring haemostasis within 30 days. The secondary outcomes were 30-day blood transfusion requirement and new thromboembolic event.

Results

Apixaban was associated with lower PPB risk than warfarin (adjusted HR (aHR) 0.39, 95% CI 0.24 to 0.63, p<0.001). Dabigatran (aHR 2.23, 95% CI 1.04 to 4.77, adjusted p (ap)=0.035) and rivaroxaban (aHR 2.72, 95% CI 1.35 to 5.48, ap=0.002) were associated with higher PPB risk than apixaban. In subgroup analysis, apixaban was associated with lower PPB risk in patients aged ≥70 years and patients with right-sided colonic polyps.

For thromboembolic events, apixaban was associated with lower risk than warfarin (aHR 0.22, 95% CI 0.11 to 0.45, p<0.001). Dabigatran (aHR 2.60, 95% CI 1.06 to 6.41, ap=0.033) and rivaroxaban (aHR 2.96, 95% CI 1.19 to 7.37, ap =0.013) were associated with higher thromboembolic risk than apixaban.

Conclusions

Apixaban was associated with a significantly lower risk of PPB and thromboembolism than warfarin, dabigatran and rivaroxaban, particularly in older patients with right-sided polyps.
Insights from behavioural economics for effective leadership during the pandemic
Authors: Schwartz Janet , Holzwarth Aline
Published: February 2021

The novel coronavirus and related COVID-19 pandemic have introduced unprecedented public policy and health challenges. In addition, healthcare consumers and workers face poor coordination by government and health officials, who lack consensus on critical elements that range from understanding risks and managing uncertainty to crafting responses that could help safely guide their constituents. As such, healthcare organisations increasingly look to their own leaders to successfully steer patients and workers through the crisis. Insights from behavioural economics can help healthcare leaders communicate information to their constituents as they make important and difficult decisions under situations of risk and uncertainty. Understanding how people interpret information about risk and uncertainty, and how they might respond to strategies that help them contextualise this information through defaults and social norms, can lead to better outcomes in patient health, employee safety and well-being and overall health system utilisation. Leaders who effectively leverage these insights may chart a clearer path towards desirable short-term and long-term organisational outcomes.
Epigallocatechin-3-gallate inhibits proliferation and triggers apoptosis in colon cancer via the hedgehog/phosphoinositide 3-kinase pathways
Authors: Ding Feng , Yang Su
Published: February 2021

The present study evaluated whether epigallocatechin-3-gallate (EGCG) effectively attenuates tumor growth in colon cancer cells and in the xenografts of nude mice and investigated the underlying mechanisms by focusing on the sonic hedgehog (Shh) and phosphoinositide 3-kinase (PI3K) pathways. Three kinds of colon cancer cells and BALB/c nude mice were used to evaluate the antiproliferative effect of EGCG. The apoptosis, migration, and invasion of colon cancer cells were analyzed to explore the toxicity effect of EGCG on colon cancer cells. Western blotting was used to demonstrate the expression levels of related proteins. The results showed that EGCG exhibited an antiproliferative effect against colon cancer cells in a dose-dependent manner with low toxicity against normal colon epithelial cells. Administration of EGCG caused significant apoptosis and inhibited the migration and invasion of colon cancer cells. The toxic effect of EGCG on colon cancer cells was accompanied by downregulation of the Shh and PI3K/Akt pathways. In addition, EGCG reduced tumor volume and weight without affecting the body weight of nude mice and inhibited the activation of the Shh and PI3K/AKT pathways in tumor tissue. Further study showed that purmorphamine (smoothened (Smo) agonist) or insulin like growth factor-1 (IGF-1, PI3K agonist) partly abolished the effect of EGCG on cell proliferation, migration, and apoptosis. Cyclopamine (Smo inhibitor) and LY294002 (PI3K inhibitor) showed the similar toxic effects as EGCG on colon cancer cells. In conclusion, EGCG inhibited colon tumor growth via downregulation of the Shh and PI3K pathways and may be a potential chemotherapeutic agent against colon cancer.
Quercetin modulates NRF2 and NF-κB/TLR-4 pathways to protect against isoniazid- and rifampicin-induced hepatotoxicity in vivo
Authors: Sanjay Sukumaran , Girish Chandrashekaran , Toi Pampa Ch , Bobby Zachariah
Published: February 2021

Isoniazid and rifampicin are crucial for treating tuberculosis (TB); however, they can cause severe hepatotoxicity leading to liver failure. Therapeutic options are limited and ineffective. We hypothesized that prophylaxis with quercetin attenuates isoniazid- and rifampicin-induced liver injury. We randomly divided Wistar rats into seven groups (n = 6). The animals received isoniazid and rifampicin or were co-treated with quercetin or silymarin for 28 days. The protective effect of quercetin was assessed using liver function tests and liver histology. Nuclear factor erythroid 2-related factor 2 (NRF2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways were explored to elucidate the mechanism of action. Quercetin co-administration prevented the elevation of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and bilirubin compared with isoniazid and rifampicin treatment alone. In the histological analysis, we observed that quercetin prophylaxis lessened the severity of hepatic necrosis and inflammation compared with the anti-TB drug–treated group. Quercetin attenuated anti-TB drug–induced oxidative stress by increasing NRF2 activation and expression, boosting endogenous antioxidant levels. Additionally, quercetin blocked inflammatory mediators high mobility group box-1 (HMGB-1) and interferon γ (IFN-γ), inhibiting activation of the NF-κB/ toll like receptor 4 (TLR-4) axis. Quercetin protects against anti-TB liver injury by activating NRF2 and blocking NF-κB/TLR-4.
Chern-Yamabe problem and Chern-Yamabe soliton
Authors: Ho Pak Tung , Shin Jinwoo
Published: February 2021

Let [Formula: see text] be a compact complex manifold of complex dimension [Formula: see text] endowed with a Hermitian metric [Formula: see text]. The Chern-Yamabe problem is to find a conformal metric of [Formula: see text] such that its Chern scalar curvature is constant. In this paper, we prove that the solution to the Chern-Yamabe problem is unique under some conditions. On the other hand, we obtain some results related to the Chern-Yamabe soliton.
The reduced Dijkgraaf–Witten invariant of twist knots in the Bloch group of a finite field
Authors: Karuo Hiroaki
Published: February 2021

Let [Formula: see text] be a closed oriented 3-manifold and let [Formula: see text] be a discrete group. We consider a representation [Formula: see text]. For a 3-cocycle [Formula: see text], the Dijkgraaf–Witten invariant is given by [Formula: see text], where [Formula: see text] is the map induced by [Formula: see text], and [Formula: see text] denotes the fundamental class of [Formula: see text]. Note that [Formula: see text], where [Formula: see text] is the map induced by [Formula: see text], we consider an equivalent invariant [Formula: see text], and we also regard it as the Dijkgraaf–Witten invariant. In 2004, Neumann described the complex hyperbolic volume of [Formula: see text] in terms of the image of the Dijkgraaf–Witten invariant for [Formula: see text] by the Bloch–Wigner map from [Formula: see text] to the Bloch group of [Formula: see text].

In this paper, by replacing [Formula: see text] with a finite field [Formula: see text], we calculate the reduced Dijkgraaf–Witten invariants of the complements of twist knots, where the reduced Dijkgraaf–Witten invariant is the image of the Dijkgraaf–Witten invariant for SL[Formula: see text] by the Bloch–Wigner map from [Formula: see text] to the Bloch group of [Formula: see text].
AUTOMATED SCREENING OF DIABETIC RETINOPATHY WITH OPTIMIZED DEEP CONVOLUTIONAL NEURAL NETWORK: ENHANCED MOTH FLAME MODEL
Authors: NAIR ARUN T , MUTHUVEL K.
Published: February 2021

Nowadays, analysis on retinal image exists as one of the challenging area for study. Numerous retinal diseases could be recognized by analyzing the variations taking place in retina. However, the main disadvantage among those studies is that, they do not have higher recognition accuracy. The proposed framework includes four phases namely, (i) Blood Vessel Segmentation (ii) Feature Extraction (iii) Optimal Feature Selection and (iv) Classification. Initially, the input fundus image is subjected to blood vessel segmentation from which two binary thresholded images (one from High Pass Filter (HPF) and other from top-hat reconstruction) are acquired. These two images are differentiated and the areas that are common to both are said to be the major vessels and the left over regions are fused to form vessel sub-image. These vessel sub-images are classified with Gaussian Mixture Model (GMM) classifier and the resultant is summed up with the major vessels to form the segmented blood vessels. The segmented images are subjected to feature extraction process, where the features like proposed Local Binary Pattern (LBP), Gray-Level Co-Occurrence Matrix (GLCM) and Gray Level Run Length Matrix (GLRM) are extracted. As the curse of dimensionality seems to be the greatest issue, it is important to select the appropriate features from the extracted one for classification. In this paper, a new improved optimization algorithm Moth Flame with New Distance Formulation (MF-NDF) is introduced for selecting the optimal features. Finally, the selected optimal features are subjected to Deep Convolutional Neural Network (DCNN) model for classification. Further, in order to make the precise diagnosis, the weights of DCNN are optimally tuned by the same optimization algorithm. The performance of the proposed algorithm will be compared against the conventional algorithms in terms of positive and negative measures.
Novel Roadside Unit Positioning Framework in the Context of the Vehicle-to-Infrastructure Communication System Based on AHP — Entropy for Weighting and Borda — VIKOR for Uniform Ranking
Authors: Malik R. Q. , Zaidan A. A. , Zaidan B. B. , Ramli K. N. , Albahri O. S. , Kareem Z. H. , Ameen H. A. , Garfan S. S. , Mohammed A. , Zaidan R. A. , Salih M. M.
Published: February 2021

The positioning of roadside units (RSUs) in a vehicle-to-infrastructure (V2I) communication system may have an impact on network performance. Optimal RSU positioning is required to reduce cost and maintain the quality of service. However, RSU positioning is considered a difficult task because numerous criteria, such as the cost of RSUs, the intersection area and communication strength, affect the positioning process and must be considered. Furthermore, the conflict and trade-off amongst these criteria and the significance of each criterion are reflected on the RSU positioning process. Thus, this work proposes a new RSU positioning framework based on multicriteria decision-making (MCDM) in the context of the V2I communication system. Three stages are completed for this purpose. First, a real-time V2I hardware is developed to collect data. The developed hardware consists of multiple mobile nodes (i.e., cars with sending–receiving hardware devices) and physical RSUs. The RSUs and the devices in the cars are connected via the nRF24L01[Formula: see text]PA/LNA transceiver module with Arduino Uno. Second, seven testing scenarios are identified toward acquiring the required data upon the connection of the V2I devices. Moreover, three evaluation attributes (i.e., number of packet losses [PKL], cost and ratio of intersection area [RIA]) are used to evaluate each scenario. A decision matrix is constructed on the basis of the crossover between ‘RSU positioning scenarios’ and ‘multi-evaluation attributes (i.e., PKL, cost and RIA)’. Third, the RSU positioning scenarios are ranked using MCDM techniques, such as the integrated analytic hierarchy process (AHP), entropy and group Vlsekriterijumska Optimizacija I Kompromisno Resenje (VIKOR). Furthermore, the Borda voting approach is used to aggregate multiple individual rankings into a uniform and final rank. Results indicate the following: (1) integrating AHP, entropy and VIKOR is effective for solving RSU positioning problems; (2) the VIKOR ranking results for individuals vary; (3) the rank of scenarios obtained from the group-VIKOR-based Borda voting context shows that the second scenario, which consists of four RSUs distributed along the street with a maximum distance of 200[Formula: see text]m between them and 2-m high antennas, is the best in terms of optimally placing the RSUs; and (4) significant differences are observed amongst the scores of the groups, indicating that the ranking results are valid.
Detour polynomials of vertex coalenscence and bridges coalenscence graphs
Authors: Ahmed Haveen J. , Ali Ahmed M. , Mohammed Saleh Gashaw A.
Published: February 2021

The length of a longest [Formula: see text] path in a connected graph [Formula: see text] is called detour distance and denoted by [Formula: see text], where the vertices [Formula: see text] and [Formula: see text] belong to the vertex set [Formula: see text]. In this paper, we find detour polynomial and detour index of [Formula: see text] connected vertex disjoint graphs, for [Formula: see text] by the vertices identified and edges introducing with isolated vertex. Also, we find detour polynomial and detour index for some compound graphs from special graphs.
Marie Byrd Land lithospheric mantle: a review of the xenolith record
Authors: Handler Monica R. , Wysoczanski Richard J. , Gamble John A.
Published: February 2021

The Marie Byrd Land (MBL) lithospheric mantle xenolith record comprises over 100 samples from a range of localities spanning both major crustal terranes that comprise MBL: Ross and Amundsen provinces. Coarse granular to porphyroclastic in texture, the xenoliths are predominantly Type I spinel-bearing lherzolites to harburgites, but include rare dunite and pyroxenite examples. Garnet is absent and no hydrous phases, such as amphibole or mica, have been reported to date, although traces of apatite may be present. Characterisation of the lithospheric mantle composition and its evolution however, is hampered by patchy and uneven geochemical analyses across the xenolith suite. Nonetheless, a picture emerges of a heterogeneous lithosphere beneath both Ross and Amundsen Provinces. Previously published and new data reported here are consistent with samples ranging from variably cryptically metasomatized residua from variable (10–25%) degrees of partial melt extraction to refertilized compositions. Limited isotopic data point to a complex history, providing evidence for both ancient Proterozoic lithospheric mantle and preservation of Ordovician events. The Sr–Nd–Pb composition of the sampled lithospheric mantle overlaps the common low-µ isotopic endmember identified in Cenozoic magmatism from MBL and the wider West Antarctic Rift System.
Educational interventions and female enrollment in IT degrees
Authors: Molnar Andreea , Keane Therese , Stockdale Rosemary
Published: February 2021

A study of female students enrolled in IT degrees in Australia traces how programs influenced decision making.
Cyber reconnaissance techniques
Authors: Mazurczyk Wojciech , Caviglione Luca
Published: February 2021

The evolution of and countermeasures for …
A second conversation with Werner Vogels
Authors: CACM Staff
Published: February 2021

The Amazon CTO sits with Tom Killalea to discuss designing for evolution at scale.
Awakening
Authors: Clegg Brian
Published: February 2021

From the intersection of computational science and technological speculation, with boundaries limited only by our ability to imagine what could be.

Some technical support will never change.
What to do about deepfakes
Authors: Johnson Deborah G. , Diakopoulos Nicholas
Published: February 2021

Seeking to reap the positive uses of synthetic media while minimizing or preventing negative societal impact.
Science is not another opinion
Authors: Denning Peter J. , Johnson Jeffrey
Published: February 2021

The issue is not who has the "truth," but whose claims deserve more credence.
SUGAR
Authors: Yang Lishan , Nie Bin , Jog Adwait , Smirni Evgenia
Published: February 2021

As Graphics Processing Units (GPUs) are becoming a de facto solution for accelerating a wide range of applications, their reliable operation is becoming increasingly important. One of the major challenges in the domain of GPU reliability is to accurately measure GPGPU application error resilience. This challenge stems from the fact that a typical GPGPU application spawns a huge number of threads and then utilizes a large amount of potentially unreliable compute and memory resources available on the GPUs. As the number of possible fault locations can be in the billions, evaluating every fault and examining its effect on theapplication error resilience is impractical. Application resilience is evaluated via extensive fault injection campaigns based on sampling of an extensive fault site space. Typically, the larger the input of the GPGPU application, the longer the experimental campaign. In this work, we devise a methodology, SUGAR (Speeding Up GPGPU Application Resilience Estimation with input sizing), that dramatically speeds up the evaluation of GPGPU application error resilience by judicious input sizing. We show how analyzing a small fraction of the input is sufficient to estimate the application resilience with high accuracy and dramatically reduce the duration of experimentation. Key of our estimation methodology is the discovery of repeating patterns as a function of the input size. Using the well-established fact that error resilience in GPGPU applications is mostly determined by the dynamic instruction count at the thread level, we identify the patterns that allow us to accurately predict application error resilience for arbitrarily large inputs. For the cases that we examine in this paper, this new resilience estimation mechanism provides significant speedups (up to 1336 times) and 97.0 on the average, while keeping estimation errors to less than 1%.
A Look Behind the Curtain: Traffic Classification in an Increasingly Encrypted Web
Authors: Akbari Iman , Salahuddin Mohammad A. , Ven Leni , Limam Noura , Boutaba Raouf , Mathieu Bertrand , Moteau Stephanie , Tuffin Stephane
Published: February 2021

Traffic classification is essential in network management for operations ranging from capacity planning, performance monitoring, volumetry, and resource provisioning, to anomaly detection and security. Recently, it has become increasingly challenging with the widespread adoption of encryption in the Internet, e.g., as a de-facto in HTTP/2 and QUIC protocols. In the current state of encrypted traffic classification using Deep Learning (DL), we identify fundamental issues in the way it is typically approached. For instance, although complex DL models with millions of parameters are being used, these models implement a relatively simple logic based on certain header fields of the TLS handshake, limiting model robustness to future versions of encrypted protocols. Furthermore, encrypted traffic is often treated as any other raw input for DL, while crucial domain-specific considerations exist that are commonly ignored. In this paper, we design a novel feature engineering approach that generalizes well for encrypted web protocols, and develop a neural network architecture based on Stacked Long Short-Term Memory (LSTM) layers and Convolutional Neural Networks (CNN) that works very well with our feature design. We evaluate our approach on a real-world traffic dataset from a major ISP and Mobile Network Operator. We achieve an accuracy of 95% in service classification with less raw traffic and smaller number of parameters, out-performing a state-of-the-art method by nearly 50% fewer false classifications. We show that our DL model generalizes for different classification objectives and encrypted web protocols. We also evaluate our approach on a public QUIC dataset with finer and application-level granularity in labeling, achieving an overall accuracy of 99%.
Input-Dynamic Distributed Algorithms for Communication Networks
Authors: Foerster Klaus-Tycho , Korhonen Janne H. , Paz Ami , Rybicki Joel , Schmid Stefan
Published: February 2021

Consider a distributed task where the communication network is fixed but the local inputs given to the nodes of the distributed system may change over time. In this work, we explore the following question: if some of the local inputs change, can an existing solution be updated efficiently, in a dynamic and distributed manner? To address this question, we define the batch dynamic \congest model in which we are given a bandwidth-limited communication network and a dynamic edge labelling defines the problem input. The task is to maintain a solution to a graph problem on the labeled graph under batch changes. We investigate, when a batch of α edge label changes arrive, \beginitemize \item how much time as a function of α we need to update an existing solution, and \item how much information the nodes have to keep in local memory between batches in order to update the solution quickly. \enditemize Our work lays the foundations for the theory of input-dynamic distributed network algorithms. We give a general picture of the complexity landscape in this model, design both universal algorithms and algorithms for concrete problems, and present a general framework for lower bounds. In particular, we derive non-trivial upper bounds for two selected, contrasting problems: maintaining a minimum spanning tree and detecting cliques.
Benign Paroxysmal Positional Vertigo and the Increased Risk of Ischemic Stroke: A Nested Case‐Control Study Using a National Cohort Sample
Authors: Choi Hyo Geun , Kim So Young
Published: February 2021

A recent population cohort study reported that benign paroxysmal positional vertigo (BPPV) was a risk factor for ischemic stroke. This study investigated the risk of ischemic and hemorrhagic strokes in patients with BPPV. A nested case‐control study used the data from the Korean National Health Insurance Service‐National Sample Cohort between 2002 and 2013. We used data of patients aged ≥50 years obtained from the Korean National Health Insurance Service‐National Sample Cohort between 2002 and 2013. A total of 15,610 patients with ischemic stroke and 4,923 patients with hemorrhagic stroke were matched for age, sex, income, residential location, hypertension, diabetes, and dyslipidemia with 62,440 and 19,692 controls, respectively. History of BPPV was evaluated in the stroke and control groups. Crude and adjusted odds ratios (ORs) for stroke in patients with BPPV were analyzed using stratified logistic regression analysis. Subgroup analyses were performed for age and sex. Notably, 3.7% (572/15,610) of patients with ischemic stroke and 2.7% (1,702/62,440) of the control subjects reported a history of BPPV (P < 0.001). The adjusted OR for BPPV in patients with ischemic stroke was 1.35 (95% confidence interval (CI) 1.22–1.49, P < 0.001). Patients with ischemic stroke showed higher ORs for BPPV in the subgroup of women. Patients with hemorrhagic stroke did not show a high OR for BPPV. Ischemic stroke patients demonstrated the increased OR for BPPV in subjects aged ≥50 years old.
Motion‐Compensated Frame Interpolation Using Cellular Automata‐Based Motion Vector Smoothing
Authors: Li Ran , Yin Ying , Sun Fengyuan , Li Yanling , You Lei
Published: February 2021

Motion‐Compensated Frame Interpolation (MCFI) is one of the common temporal‐domain tamper operations, and it is used to produce faked video frames for improving the visual qualities of video sequences. The instability of temporal symmetry results in many incorrect Motion Vectors (MVs) for Bidirectional Motion Estimation (BME) in MCFI. The existing Motion Vector Smoothing (MVS) works often oversmooth or revise correct MVs as wrong ones. To overcome this problem, we propose a Cellular Automata‐based MVS (CA‐MVS) algorithm to smooth the Motion Vector Field (MVF) output by BME. In our work, a cellular automaton is constructed to deduce MV outliers according to a defined local evolution rule. By performing CA‐based evolution in a loop iteration, we gradually expose MV outliers and reduce incorrect MVs resulting from oversmoothing as many as possible. Experimental results show the proposed algorithm can improve the accuracy of BME and provide better objective and subjective interpolation qualities when compared with the traditional MVS algorithms.
On

L

2

-Boundedness of
h
-Pseudodifferential Operators
Authors: Yang Jie
Published: February 2021

Let

T

a

h

be the

h

-pseudodifferential operators with symbol

a

. When

a
∈

S

ρ
,
1

m

and

m
=
n

ρ
−
1

/
2

, it is well known that

T

a

h

is not always bounded in

L

2

ℝ

n

. In this paper, under the condition

a

x
,
ξ

∈

L

∞

S

ρ

n

ρ
−
1

/
2

ω

, we show that

T

a

h

is bounded on

L

2

.
Prediction and Analysis of Protein Ubiquitin Sites in the Model Plant A. thaliana
Authors: Shan Shujun , Qi Yue , Jiang Jihong , Guo Song
Published: February 2021

Ubiquitin is an important type of protein after translational modification. Ubiquitin has the ability to take part in several cellular regulations among several biological processions. At the same time, ubiquitin plays key roles in the enzymatic process. So as to construct the new tool to classify the ubiquitin amino acid residues, we employed the random forest model to classify the ubiquitin sites utilizing the experimentally identified ubiquitinated protein sequences of A. thaliana. More detailed, we utilized the k-spaced amino acid pair (CKSAAP) encoding and binary encoding to deal with the potential protein segments. The proposed tools can obtain 72.83% in Sp, 72.42% in Sn, 72.63% in Acc, and 0.4525 in MCC. With these performances, such tools can obtain the available results in the dataset of Arabidopsis.
Dexmedetomidine Induced Polyuria in the Intensive Care Unit
Authors: Uddin Mohammed M. , Sebastian Joseph , Usama Muhammad , Raziq Fazal I. , Saydain Ghulam , Rossi Noreen F.
Published: February 2021

Dexmedetomidine is an α2-adrenergic used as an adjunct therapy for sedation in the intensive care unit. While it is known to cause polyuria exclusively in perioperative conditions, not many cases are known in the intensive care unit, thus making the diagnosis challenging. We present the case of a 61-year-old male who had developed polyuria secondary to central diabetes insipidus after receiving dexmedetomidine intravenous infusion in the medical ICU. Increased awareness of this uncommon side effect of dexmedetomidine will help clinicians recognize and address it early.
NPM–ALK-Induced Reprogramming of Mature TCR-Stimulated T Cells Results in Dedifferentiation and Malignant Transformation
Authors: Pawlicki Jan M. , Cookmeyer David L. , Maseda Damian , Everett John K. , Wei Fang , Kong Hong , Zhang Qian , Wang Hong Y. , Tobias John W. , Walter David M. , Zullo Kelly M. , Javaid Sarah , Watkins Amanda , Wasik Mariusz A. , Bushman Frederic D. , Riley James L.
Published: February 2021

Fusion genes including NPM–ALK can promote T-cell transformation, but the signals required to drive a healthy T cell to become malignant remain undefined. In this study, we introduce NPM–ALK into primary human T cells and demonstrate induction of the epithelial-to-mesenchymal transition (EMT) program, attenuation of most T-cell effector programs, reemergence of an immature epigenomic profile, and dynamic regulation of c-Myc, E2F, and PI3K/mTOR signaling pathways early during transformation. A mutant of NPM–ALK failed to bind several signaling complexes including GRB2/SOS, SHC1, SHC4, and UBASH3B and was unable to transform T cells. Finally, T-cell receptor (TCR)–generated signals were required to achieve T-cell transformation, explaining how healthy individuals can harbor T cells with NPM–ALK translocations. These findings describe the fundamental mechanisms of NPM–ALK-mediated oncogenesis and may serve as a model to better understand factors that regulate tumor formation.

Significance:

This investigation into malignant transformation of T cells uncovers a requirement for TCR triggering, elucidates integral signaling complexes nucleated by NPM–ALK, and delineates dynamic transcriptional changes as a T cell transforms.

See related commentary by Spasevska and Myklebust, p. 3160
Chr20q Amplification Defines a Distinct Molecular Subtype of Microsatellite Stable Colorectal Cancer
Authors: Zhang Baoyi , Yao Kevin , Zhou Emily , Zhang Lanjing , Cheng Chao
Published: February 2021

Colorectal cancer is the third leading cause of cancer-related death in the United States. About 15% of colorectal cancers are associated with microsatellite instability (MSI) due to loss of function in the DNA mismatch repair pathway. This subgroup of patients has better survival rates and is more sensitive to immunotherapy. However, it remains unclear whether microsatellite stable (MSS) patients with colorectal cancer can be further stratified into subgroups with differential clinical characteristics. In this study, we analyzed The Cancer Genome Atlas data and found that Chr20q amplification is the most frequent copy number alteration that occurs specifically in colon (46%) and rectum (61%) cancer and is mutually exclusive with MSI. Importantly, MSS patients with Chr20q amplification (MSS-A) were associated with better recurrence-free survival compared with MSS patients without Chr20q amplification (MSS-N; P = 0.03). MSS-A tumors were associated with high level of chromosome instability and low immune infiltrations. In addition, MSS-A and MSS-N tumors were associated with somatic mutations in different driver genes, with high frequencies of mutated TP53 in MSS-A and mutated KRAS and BRAF in MSS-N. Our results suggest that MSS-A and MSS-N represent two subtypes of MSS colorectal cancer, and such stratification may be used to improve therapeutic treatment in an individualized manner.

Significance:

This study shows that chromosome 20q amplification occurs predominately in microsatellite-stable colorectal cancer and defines a distinct subtype with good prognosis, high chromosomal instability, distinct mutation profiles, and low immune infiltrations.
Depot-Medroxyprogesterone Acetate Use Is Associated with Decreased Risk of Ovarian Cancer: The Mounting Evidence of a Protective Role of Progestins
Authors: Phung Minh Tung , Lee Alice W. , Wu Anna H. , Berchuck Andrew , Cho Kathleen R. , Cramer Daniel W. , Doherty Jennifer Anne , Goodman Marc T. , Hanley Gillian E. , Harris Holly R. , McLean Karen , Modugno Francesmary , Moysich Kirsten B. , Mukherjee Bhramar , Schildkraut Joellen M. , Terry Kathryn L. , Titus Linda J. , Jordan Susan J. , Webb Penelope M. , Pike Malcolm C. , Pearce Celeste Leigh
Published: February 2021

Background:

Combined oral contraceptive use is associated with a decreased risk of invasive epithelial ovarian cancer (ovarian cancer). There is suggestive evidence of an inverse association between progestin-only contraceptive use and ovarian cancer risk, but previous studies have been underpowered.

Methods:

The current study used primary data from 7,977 women with ovarian cancer and 11,820 control women in seven case–control studies from the Ovarian Cancer Association Consortium to evaluate the association between use of depot-medroxyprogesterone acetate (DMPA), an injectable progestin-only contraceptive, and ovarian cancer risk. Logistic models were fit to determine the association between ever use of DMPA and ovarian cancer risk overall and by histotype. A systematic review of the association between DMPA use and ovarian cancer risk was conducted.

Results:

Ever use of DMPA was associated with a 35% decreased risk of ovarian cancer overall (OR, 0.65; 95% confidence interval, 0.50–0.85). There was a statistically significant trend of decreasing risk with increasing duration of use (Ptrend < 0.001). The systematic review yielded six studies, four of which showed an inverse association and two showed increased risk.

Conclusions:

DMPA use appears to be associated with a decreased risk of ovarian cancer in a duration-dependent manner based on the preponderance of evidence. Further study of the mechanism through which DMPA use is associated with ovarian cancer is warranted.

Impact:

The results of this study are of particular interest given the rise in popularity of progestin-releasing intrauterine devices that have a substantially lower progestin dose than that in DMPA, but may have a stronger local effect.
Differential Associations of SLCO Transporters with Prostate Cancer Aggressiveness between African Americans and European Americans
Authors: Tang Li , Zhu Qianqian , Wang Zinian , Shanahan Clayton M. , Bensen Jeannette T. , Fontham Elizabeth T.H. , Smith Gary J. , Pop Elena A. , Azabdaftari Gissou , Mohler James L. , Wu Yue
Published: February 2021

Background:

Androgen receptor signaling is crucial to prostate cancer aggressiveness. Members of the solute carrier family of the organic anion transporting peptides (SLCO) are potential regulators of androgen availability in prostate tissue. It remains unknown whether genetic variations in SLCOs contribute to the differences in prostate cancer aggressiveness in African Americans (AA) and European Americans (EA).

Methods:

SNPs in 11 SLCO members were selected, with addition of 139 potentially functional SNPs and 128 ancestry informative markers. A total of 1,045 SNPs were genotyped and analyzed in 993 AAs and 1,057 EAs from the North Carolina–Louisiana Prostate Cancer Project. Expression and cellular localization of SLCOs were examined using qRT-PCR, IHC, and in situ RNA hybridization in independent sets of prostate cancer cases.

Results:

Significant associations with prostate cancer characteristics were found for SNPs in SLCO2A1 and SLCO5A1. The associations differed by race (Pinteraction < 0.05). SNPs in SLCO2A1 were associated with reduced tumor aggressiveness and low Gleason score in AAs; whereas, SNPs in SLCO5A1 were associated with high clinical stage in EAs. In prostate tissue, SLCO2A1 and SLCO5A1 were the most expressed SLCOs at the mRNA level and were expressed predominantly in prostate endothelial and epithelial cells at the protein level, respectively.

Conclusions:

SLCO2A1 and SLCO5A1 play important but different roles in prostate cancer aggressiveness in AAs versus EAs.

Impact:

The finding calls for consideration of racial differences in biomarker studies of prostate cancer and for investigations on functions of SLCO2A1 and SLCO5A1 in prostate cancer.
Lifestyle, Behavioral, and Dietary Risk Factors in Relation to Mammographic Breast Density in Women at High Risk for Breast Cancer
Authors: Ahern Thomas P. , Sprague Brian L. , Farina Nicholas H. , Tsai Erin , Cuke Melissa , Kontos Despina , Wood Marie E.
Published: February 2021

Background:

Women at high risk for breast cancer due to genetics or risk factor profiles are counseled to adopt lifestyle, behavioral, and dietary changes to help reduce their risk. These recommendations are based on studies of women at average risk, so their effectiveness in high-risk women is unclear.

Methods:

We evaluated the impact of physical activity, smoking, alcohol consumption, and intake of folate and carotenoids on mammographic breast density—a proxy for breast cancer risk—among 387 high-risk women. Exposures were self-reported on questionnaires. Breast dense area, nondense area, and percent dense area were measured from screening mammograms with Library for Breast Radiodensity Assessment software. Cross-sectional associations were estimated with multivariable quantile regression models.

Results:

After adjusting for age, adiposity, reproductive history, and use of postmenopausal hormones, no breast density measure was associated with physical activity level, smoking status, alcohol consumption, or estimated intake of folate, alpha-carotene, beta-carotene, lutein/zeaxanthin, and beta-cryptoxanthin. Lycopene intake was associated with lower dense area when comparing the highest and lowest intake categories (adjusted difference in median = −14 cm2, 95% confidence interval: −29 to 1.3 cm2). This association may be explained by incomplete adjustment for adiposity.

Conclusions:

Recommended lifestyle, behavioral, and dietary changes to mitigate personal risk of breast cancer do not substantially impact mammographic breast density measures.

Impact:

Alternative strategies, such as increased uptake of chemoprevention, may better serve risk reduction efforts in women at high risk for breast cancer.
Beta-Blockers Use and Risk of Breast Cancer in Women with Hypertension
Authors: Zheng Guoqiao , Sundquist Jan , Sundquist Kristina , Ji Jianguang
Published: February 2021

Background:

The risk of breast cancer among hypertensive patients who use beta-blockers has attracted attention. However, the evidence is inconsistent and investigation of the dose-specific associations for subtypes of beta-blockers is limited.

Methods:

By incorporating Swedish national registers, breast cancer risk was estimated in women with hypertension who used nonselective beta-blockers and beta-1 selective blockers compared with propensity score–matched nonusers. The cumulative defined daily dose was used to study the dose–response association. Test of interaction between beta-blocker use and other antihypertensive medications was performed.

Results:

Hypertensive patients taking beta-1 selective blockers (metoprolol, atenolol, bisoprolol) had an increased risk of breast cancer with a HR and 95% confidence interval (CI) of 2.39 (1.95–2.94), 2.31 (1.46–3.64), and 3.02 (2.09–4.36), respectively. All of the observed associations were dose-dependent (Ptrend < 0.0001). No significant association was found for the nonselective beta-blocker (propranolol) except that among users of agents acting on the renin–angiotensin system, those who used propranolol had increased breast cancer risk. Modification of agents acting on the renin–angiotensin system on breast cancer risk was also observed for atenolol.

Conclusions:

The increased risk of breast cancer associates with the use of beta-1 selective blockers in a dose–response manner.

Impact:

Breast cancer surveillance is recommended for hypertensive female patients using beta-1 selective blockers.
Hysterectomy and Risk of Breast, Colorectal, Thyroid, and Kidney Cancer – an Australian Data Linkage Study
Authors: Wilson Louise F. , Tuesley Karen M. , Webb Penelope M. , Dixon-Suen Suzanne C. , Stewart Louise M. , Jordan Susan J.
Published: February 2021

Background:

This study aimed to investigate the associations between hysterectomy for benign indications and risk of breast, colorectal, kidney, and thyroid cancer, and to explore whether these associations are modified by removal of ovaries at the time of surgery or by age at surgery.

Methods:

We conducted a retrospective cohort study of the female population of Western Australia (n = 839,332) linking data from electoral, hospital, births, deaths, and cancer records. We used Cox regression to estimate HRs and 95% confidence intervals (CI) for the associations between hysterectomy and diagnosis of breast, colorectal, kidney, and thyroid cancers.

Results:

Compared with no surgery, hysterectomy without oophorectomy (hysterectomy) and hysterectomy with bilateral salpingo-oophorectomy (hysterectomy-BSO) were associated with higher risk of kidney cancer (HR, 1.32; 95% CI, 1.11–1.56 and HR, 1.29; 95% CI, 0.96–1.73, respectively). Hysterectomy, but not hysterectomy-BSO, was related to higher risk of thyroid cancer (HR, 1.38; 95% CI, 1.19–1.60). In contrast, hysterectomy (HR, 0.94; 95% CI, 0.90–0.98) and hysterectomy-BSO (HR, 0.92; 95% CI, 0.85–1.00) were associated with lower risk of breast cancer. We found no association between hysterectomy status and colorectal cancer.

Conclusions:

The associations between hysterectomy and cancer varied by cancer type with increased risks for thyroid and kidney cancer, decreased risk for breast cancer, and no association for colorectal cancer.

Impact:

As breast, colorectal, and gynecologic cancers comprise a sizeable proportion of all cancers in women, our results suggest that hysterectomy is unlikely to increase overall cancer risk; however, further research to understand the higher risk of thyroid and kidney cancer is warranted.
Paracrine Placental Growth Factor Signaling in Response to Ionizing Radiation Is p53-Dependent and Contributes to Radioresistance
Authors: Kazimova Tamara , Tschanz Fabienne , Sharma Ashish , Telarovic Irma , Wachtel Marco , Pedot Gloria , Schäfer Beat , Pruschy Martin
Published: February 2021

Placental growth factor (PlGF) is a pro-angiogenic, N-glycosylated growth factor, which is secreted under pathologic situations. Here, we investigated the regulation of PlGF in response to ionizing radiation (IR) and its role for tumor angiogenesis and radiosensitivity. Secretion and expression of PlGF was induced in multiple tumor cell lines (medulloblastoma, colon and lung adenocarcinoma) in response to irradiation in a dose- and time-dependent manner. Early upregulation of PlGF expression and secretion in response to irradiation was primarily observed in p53 wild-type tumor cells, whereas tumor cells with mutated p53 only showed a minimal or delayed response. Mechanistic investigations with genetic and pharmacologic targeting of p53 corroborated regulation of PlGF by the tumor suppressor p53 in response to irradiation under normoxic and hypoxic conditions, but with so far unresolved mechanisms relevant for its minimal and delayed expression in tumor cells with a p53-mutated genetic background. Probing a paracrine role of IR-induced PlGF secretion in vitro, migration of endothelial cells was specifically increased towards irradiated PlGF wild type but not towards irradiated PlGF-knockout (PIGF-ko) medulloblastoma cells. Tumors derived from these PlGF-ko cells displayed a reduced growth rate, but similar tumor vasculature formation as in their wild-type counterparts. Interestingly though, high-dose irradiation strongly reduced microvessel density with a concomitant high rate of complete tumor regression only in the PlGF-ko tumors.

Implications:

Our study shows a strong paracrine vasculature-protective role of PlGF as part of a p53-regulated IR-induced resistance mechanism and suggest PlGF as a promising target for a combined treatment modality with RT.