bluuebunny/crossref_metadata_2025 huggingface dataset:
Overlap of high-risk individuals predicted by family history, and genetic and non-genetic breast cancer risk prediction models: implications for risk stratification
Authors: Ho Peh Joo , Ho Weang Kee , Khng Alexis J. , Yeoh Yen Shing , Tan Benita Kiat-Tee , Tan Ern Yu , Lim Geok Hoon , Tan Su-Ming , Tan Veronique Kiak Mien , Yip Cheng-Har , Mohd-Taib Nur-Aishah , Wong Fuh Yong , Lim Elaine Hsuen , Ngeow Joanne , Chay Wen Yee , Leong Lester Chee Hao , Yong Wei Sean , Seah Chin Mui , Tang Siau Wei , Ng Celene Wei Qi , Yan Zhiyan , Lee Jung Ah , Rahmat Kartini , Islam Tania , Hassan Tiara , Tai Mei-Chee , Khor Chiea Chuen , Yuan Jian-Min , Koh Woon-Puay , Sim Xueling , Dunning Alison M. , Bolla Manjeet K. , Antoniou Antonis C. , Teo Soo-Hwang , Li Jingmei , Hartman Mikael
Published: April 2022

Background

Family history, and genetic and non-genetic risk factors can stratify women according to their individual risk of developing breast cancer. The extent of overlap between these risk predictors is not clear.

Methods

In this case-only analysis involving 7600 Asian breast cancer patients diagnosed between age 30 and 75 years, we examined identification of high-risk patients based on positive family history, the Gail model 5-year absolute risk [5yAR] above 1.3%, breast cancer predisposition genes (protein-truncating variants [PTV] in ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, or TP53), and polygenic risk score (PRS) 5yAR above 1.3%.

Results

Correlation between 5yAR (at age of diagnosis) predicted by PRS and the Gail model was low (r=0.27). Fifty-three percent of breast cancer patients (n=4041) were considered high risk by one or more classification criteria. Positive family history, PTV carriership, PRS, or the Gail model identified 1247 (16%), 385 (5%), 2774 (36%), and 1592 (21%) patients who were considered at high risk, respectively. In a subset of 3227 women aged below 50 years, the four models studied identified 470 (15%), 213 (7%), 769 (24%), and 325 (10%) unique patients who were considered at high risk, respectively. For younger women, PRS and PTVs together identified 745 (59% of 1276) high-risk individuals who were not identified by the Gail model or family history.

Conclusions

Family history and genetic and non-genetic risk stratification tools have the potential to complement one another to identify women at high risk.
MiR-212 value in prognosis and diagnosis of cancer and its association with patient characteristics: a systematic review and meta-analysis
Authors: Raji Sara , Sahranavard Mehrdad , Mottaghi Mahdi , Sahebkar Amirhossein
Published: April 2022

Background

Delayed cancer diagnosis and inefficient cancer prognosis determination are problems faced in cancer diagnosis and treatment. MicroRNAs (miRs), especially miR-212, have shown a promise in cancer diagnosis and prognosis. Herein, we performed a systematic review and meta-analysis to assess the prognostic and diagnostic value of miR-212 level in cancer and evaluated its association with patient characteristics.

Methods

A fully electronic literature search using related keywords was performed in PubMed, Scopus, Web of Science, Embase, and ScienceDirect databases by June 6, 2021, with no time or language restriction. Meta-analysis was performed to pool survival prognosis data using hazard ratio (HR), association using odds ratio (OR), and diagnostic data using sensitivity, specificity, and diagnostic odds ratio (DOR). Sub-group analysis and meta-regression were performed as appropriate.

Results

Results of 28 studies on 1880 patients showed a poor cancer prognosis with high levels of miR-212 in pancreatic ductal adenocarcinoma (PDAC, HR = 2.451 [1.447–4.149]), and a poor cancer prognosis with low levels of miR-212 in other cancers (HR = 2.514 [2.162–2.923]). Higher alpha-fetoprotein (AFP) level and Edmondson-Steiner grade were factors associated with miR-212 low level incidence. Diagnostic odds ratio 10.688 (3.644–31.348) and SROC AUC of 0.84 confirmed high diagnostic performance of miR-212.

Conclusion

Our systematic review and meta-analysis results confirm miR-212 high value in cancer prognosis and diagnosis. High level of miR-212 showed poor prognosis in PDAC and low level of miR-212 showed poor prognosis in other cancers. in conclusion, miR-212 could be a novel potential biomarker in cancer diagnosis and prognosis.
PDGF-BB-derived supramolecular hydrogel for promoting skin wound healing
Authors: Jian Ke , Yang Chenghao , Li Tingting , Wu Xia , Shen Jun , Wei Jiaying , Yang Zhimou , Yuan Dan , Zhao Mingyi , Shi Junfeng
Published: April 2022

Chronic wounds represent a major challenge to the present healthcare system. In recent decades, many topical therapies have been investigated for the treatment of chronic wounds, including different types of wound dressings, antimicrobial agents, and cell therapy. Platelet-derived growth factor (PDGF) plays an important role in wound healing and has been approved for treatment of wounds related to diabetes mellitus. However, the high cost and short retention time of PDGF protein have limited its wide application. To overcome this challenge, we designed a PDGF-mimicking peptide by connecting PDGF epitope VRKIEIVRKK and self-assembling motif derived from β-amyloid peptide. The resultant peptide can self-assemble into a fibril-rich network and leads to supramolecular hydrogelation with good stability. The hydrophilic epitope can be exposed on the surface of nanofibrils, which might contribute to the binding and activation of PDGF receptors. The forming hydrogel is able to induce the growth and migration of vascular endothelial cells and promote the formation of vascular branches. In the full-thickness skin wounds of healthy mice, after the application of the hydrogel, the density of neovascularization marked by CD31 was greater than that in the control group on Day 3. Larger collagen deposition and a thicker epidermis were observed on Day 12. These results demonstrate that the hydrogel can stimulate collagen deposition and angiogenesis, enhance skin regeneration, and show an excellent therapeutic effect. Taken together, this work not only provides new insight into the design of bioactive peptides but also offers a promising biomaterial for wound healing.
A nomogram for predicting paradoxical immune reconstitution inflammatory syndrome associated with cryptococcal meningitis among HIV-infected individuals in China
Authors: Han Xiaoxu , Liu Hui , Wang Yuqi , Wang Peng , Wang Xin , Yi Yunyun , Li Xin
Published: April 2022

Background

Cryptococcal meningitis (CM) associated immune reconstitution inflammatory syndrome (CM-IRIS) is the second most common complication in HIV-infected individuals with cryptococcal meningitis, with a reported mortality rate ranging from 8 to 30%. Given the devastating consequences of CM-IRIS related intracranial neuroinflammation and its challenging in diagnosis, we conducted a study to explore the risk factors and the occurrence of paradoxical CM-IRIS in HIV-infected patients, which is of great value for prevention and clinical management.

Methods

We conducted a retrospective cohort study to identify the indicators associated with paradoxical CM-IRIS among 86 HIV-infected patients with CM using univariate and multivariate cox analysis. A nomogram was constructed using selected variables to evaluate the occurrence of paradoxical CM-IRIS at 6 months and 12 months after ART initiation. The discrimination and calibration of the nomogram were assessed by concordance index (C-index) and calibration plots. Decision curves analysis (DCA) were used to evaluate clinical effectiveness of the nomogram. Subsequently, to help clinicians recognize patients at high risk faster, patients were divided into high-risk and low-risk groups according to the best cutoff point identified by X-tile.

Results

Of 86 AIDS patients with CM, 22.1% experienced paradoxical CM-IRIS at a median of 32 days after antiretroviral therapy (ART) initiation. The occurrence of paradoxical CM-IRIS was associated with age, ART initiation within 4 weeks of antifungal treatment, a four-fold increase in CD4 T cell counts, C-reactive protein levels, and hemoglobin levels independently. These five variables were further used to construct a predictive nomogram. The C-index (0.876) showed the favorable discriminative ability of the nomogram. The calibration plot revealed a high consistency between the predicted and actual observations. DCA showed that the nomogram was clinically useful. Risk stratification based on the total score of the nomogram showed well-differentiated in the high-risk and low-risk groups. Clinicians should pay attention to patients with total points high than 273.

Conclusions

We identified the predictive factors of paradoxical CM-IRIS and constructed a nomogram to evaluate the occurrence of paradoxical CM-IRIS in 6 months and 12 months. The nomogram represents satisfactory performance and might be applied clinically to the screening and management of high-risk patients.
Prenatal diagnosis and genetic counseling of a uniparental isodisomy of chromosome 8 with no phenotypic abnormalities
Authors: Yu Chunjiao , Tian Ying , Qi Liang , Wang Bo
Published: April 2022

Background

Uniparental disomy (UPD) refers to an epigenomic abnormality in which both copies of, or a part of, a homologous pair of chromosomes are inherited from one parent. UPD arises via a number of mechanisms, including monosomic and trisomic rescue (in embryonic development), incomplete segregation of chromosomes, and mitotic recombination.

Case presentation

A 34-year-old, gravida 2, para 0 woman underwent amniocentesis at 18 weeks of gestation because the noninvasive prenatal testing (NIPT) showed the highly possibility of trisomy chromosome 8. GTG-banding karyotype analysis was performed on cultured amniocytes. Chromosomal microarray analysis (CMA), fluorescence in situ hybridization(FISH), whole-exome sequencing(WES) on uncultured amniocytes were performed.

Results

CMA detected a 29.4 Mb uniparental isodisomy of chromosome 8, arr 8p23.3p12(168484_29427840) × 2 hmz [GRCh37(hg19)]. FISH, WES and ultrasound examination showed no abnormal. At the 36-month checkup, the baby was developing normally.

Conclusion

Combination of NIPT,prenatal ultrasound, karyotype analysis, CMA, FISH, WES and genetic counseling will prove a more accurate risk assessment for the prenatal diagnosis of UPD.
Comprehensive enhancer-target gene assignments improve gene set level interpretation of genome-wide regulatory data
Authors: Qin Tingting , Lee Christopher , Li Shiting , Cavalcante Raymond G. , Orchard Peter , Yao Heming , Zhang Hanrui , Wang Shuze , Patil Snehal , Boyle Alan P. , Sartor Maureen A.
Published: April 2022

Background

Revealing the gene targets of distal regulatory elements is challenging yet critical for interpreting regulome data. Experiment-derived enhancer-gene links are restricted to a small set of enhancers and/or cell types, while the accuracy of genome-wide approaches remains elusive due to the lack of a systematic evaluation. We combined multiple spatial and in silico approaches for defining enhancer locations and linking them to their target genes aggregated across >500 cell types, generating 1860 human genome-wide distal enhancer-to-target gene definitions (EnTDefs). To evaluate performance, we used gene set enrichment (GSE) testing on 87 independent ENCODE ChIP-seq datasets of 34 transcription factors (TFs) and assessed concordance of results with known TF Gene Ontology annotations, and other benchmarks.

Results

The top ranked 741 (40%) EnTDefs significantly outperform the common, naïve approach of linking distal regions to the nearest genes, and the top 10 EnTDefs perform well when applied to ChIP-seq data of other cell types. The GSE-based ranking of EnTDefs is highly concordant with ranking based on overlap with curated benchmarks of enhancer-gene interactions. Both our top general EnTDef and cell-type-specific EnTDefs significantly outperform seven independent computational and experiment-based enhancer-gene pair datasets. We show that using our top EnTDefs for GSE with either genome-wide DNA methylation or ATAC-seq data is able to better recapitulate the biological processes changed in gene expression data performed in parallel for the same experiment than our lower-ranked EnTDefs.

Conclusions

Our findings illustrate the power of our approach to provide genome-wide interpretation regardless of cell type.
Reduction of gastrointestinal tract colonization by Klebsiella quasipneumoniae using antimicrobial protein KvarIa
Authors: Karaliute Indre , Ramonaite Rima , Bernatoniene Jurga , Petrikaite Vilma , Misiunas Audrius , Denkovskiene Erna , Razanskiene Ausra , Gleba Yuri , Kupcinskas Juozas , Skieceviciene Jurgita
Published: April 2022

Background

Klebsiella quasipneumoniae is an opportunistic pathogen causing antibiotic-resistant infections of the gastrointestinal tract in many clinical cases. Orally delivered bioactive Klebsiella-specific antimicrobial proteins, klebicins, could be a promising method to eradicate Klebsiella species infecting the gut.

Methods

Mouse infection model was established based on infection of antibiotic-treated BALB/C mice with K. quasipneumoniae strain DSM28212. Four study groups were used (3 animals/group) to test the antimicrobial efficacy of orally delivered klebicin KvarIa: vehicle-only group (control, phosphate-buffered saline), and other three groups with bacteria, antibiotic therapy and 100 µg of uncoated Kvarla, 100 µg coated KvarIa, 1000 µg coated-KvarIa. Because of the general sensitivity of bacteriocins to gastroduodenal proteases, Kvarla doses were coated with Eudragit®, a GMP-certified formulation agent that releases the protein at certain pH. The coating treatment was selected based on measurements of mouse GI tract pH. The quantity of Klebsiella haemolysin gene (khe) in faecal samples of the study animals was used to quantify the presence of Klebsiella.

Results

GI colonization of K. quasipneumoniae was achieved only in the antibiotic-treated mice groups. Significant changes in khe marker quantification were found after the use of Eudragit® S100 formulated klebicin KvarIa, at both doses, with a significant reduction of K. quasipneumoniae colonization compared to the vehicle-only control group.

Conclusions

Mouse GI tract colonization with K. quasipneumoniae can be achieved if natural gut microbiota is suppressed by prior antibiotic treatment. The study demonstrates that GI infection caused by K. quasipneumoniae can be significantly reduced using Eudragit®-protected klebicin KvarIa.
Saturated salt solutions in showcases: humidity control and pollutant absorption
Authors: Eggert Gerhard
Published: April 2022

The sustainable, passive climatisation of display cases using saturated salt solutions is rarely applied nowadays. These solutions adjust the atmospheric humidity to the specific deliquescence relative humidity (DRH) of the salt. Practical problems like the risk of spilling or ‘creeping’ of salts can be overcome. The DRH of suitable salts does not depend significantly on temperature. Solutions were Oddy-tested to check for corrosive emissions of the acids corresponding to the salt anions. Only magnesium chloride failed in accordance with thermodynamic calculations of the HCl vapour pressure. Solutions can absorb water-soluble pollutants like acids or aldehydes from the atmosphere, as has successfully been demonstrated for formaldehyde in chamber experiments. The alkaline potassium carbonate solution not only dissolves acids and aldehydes but also reacts with them chemically. Research needs to further study the absorption of pollutants are outlined. A revival of the saturated salt solution would make museum displays more sustainable.
COVID-19 vaccines: awareness, attitude and acceptance among undergraduate University students
Authors: Asres Firew , Umeta Belachew
Published: April 2022

Background

The myths and conspiracy theories on the COVID-19 vaccine cause people to be hesitant and maleficent towards the vaccine.

Objectives

To assess COVID-19 vaccine-related awareness, attitude and acceptance and to assess reasons for refusing the vaccine among undergraduate Jimma University Institute of Health students.

Methods

A cross-sectional study was conducted among 387 undergraduate students of Jimma University Institute of Health. Self-administered questionnaires were used to collect the data and summarized by descriptive statistics. A multivariable regression model was used to assess predictable variables for good awareness and positive attitude. Apvalue of < 0.05 was used to declare the statistical association.

Results

Only 41% of the students had a good awareness of the COVID-19 vaccine, and more than half, 224 (57.9%) of them had a positive attitude towards the COVID-19 vaccine. Age [(AOR: 95% CI) 1.18 (1.03, 1.35)] and having good awareness [(AOR: 95% CI) 2.39 (1.55, 3.68)] were associated with positive attitude of students towards the COVID-19 vaccine. However, only 27.1% of the students were willing to take the vaccine for COVID-19. Afraid of long term effects (49.1%), not being convinced of the safety standards (38.8%), lack of information about the vaccine (37.2%), and too short time for development (39.9%) was common reasons for refusing the COVID-19 vaccine.

Conclusions

According to the present study, the majority of the participants had a positive attitude towards COVID-19 vaccine. However, only less than half of the participants had a good awareness of the vaccine. In addition, the acceptability of the vaccine is low. Afraid of long term effects, not being convinced of the safety profile, lack of information about the vaccine, and the time used for the development were the common reasons for refusing the vaccine. Therefore, all stakeholders are advised to increase awareness, positive attitude, and acceptance of the vaccine.
Yoga and mental health: what every psychiatrist needs to know
Authors: Bhargav Hemant , George Sanju , Varambally Shivarama
Published: April 2022

Yoga was developed primarily as a tool for self-mastery and spiritual progress. However, over the past few decades, the therapeutic applications of yoga in mental healthcare have been explored with promising results. This article aims to inform psychiatrists about the clinical usefulness of yoga for mental disorders. We discuss the rationale and latest evidence base for the use of yoga in psychiatric practice, including the neurobiological mechanisms and indications and contraindications for yoga therapy. We suggest practical yoga techniques that can be used as an add-on for managing common psychiatric conditions. Finally, we discuss the setting up and running of yoga clinical services in a tertiary psychiatric hospital in India and explore what can be learnt to facilitate yoga as a therapeutic approach in the Western world.
The acute effects of higher versus lower load duration and intensity on morphological and mechanical properties of the healthy Achilles tendon: a randomized crossover trial
Authors: Merza Eman Y. , Pearson Stephen J. , Lichtwark Glen A. , Malliaras Peter
Published: April 2022

The Achilles tendon (AT) exhibits volume changes related to fluid flow under acute load which may be linked to changes in stiffness. Fluid flow provides a mechanical signal for cellular activity and may be one mechanism that facilitates tendon adaptation. This study aimed to investigate whether isometric intervention involving a high level of load duration and intensity could maximize the immediate reduction in AT volume and stiffness compared with interventions involving a lower level of load duration and intensity. Sixteen healthy participants (12 males, 4 females; age 24.4±9.4 years, body mass 70.9±16.1 kg, height 1.7±0.1 m) performed three isometric interventions of varying levels of load duration (2 s and 8 s) and intensity (35% and 75% maximal voluntary isometric contraction) over a 3 week period. Freehand 3D ultrasound was used to measure free AT volume (at rest) and length (at 35%, 55% and 75% of maximum plantarflexion force) pre- and post-interventions. The slope of the force–elongation curve over these force levels represented individual stiffness (N mm−1). Large reductions in free AT volume and stiffness resulted in response to long-duration high-intensity loading whilst less reduction was produced with a lower load intensity. In contrast, no change in free AT volume and a small increase in AT stiffness occurred with lower load duration. These findings suggest that the applied load on the AT must be heavy and sustained for a long duration to maximize immediate volume reduction, which might be an acute response that enables optimal long-term tendon adaptation via mechanotransduction pathways.
Start-up Search Costs
Authors: Byrne David P. , de Roos Nicolas
Published: April 2022

Workhorse economic models used for studying the market impacts of search frictions assume constant search costs: individuals pay the same cost to obtain price information each time they search. This paper provides evidence on a new form of search costs: start-up costs. Exploiting a natural experiment in retail gasoline, we document how a temporary, large exogenous shock to consumers’ search incentives leads to a substantial, permanent increase in price search. A standard search model fails to explain such history dependence in search, while it follows directly from a model with a one-time up-front cost to start searching. (JEL D83, L13, L81)
Comment on “Modeling Purchasing Behavior with Sudden ‘Death’: A Flexible Customer Lifetime Model”
Authors: Adler Jost
Published: April 2022

In their 2012 paper, Bemmaor and Glady introduced the gamma/Gompertz/negative binomial distribution model for customer base analysis. Their model uses exponentially distributed interpurchase times and a Gompertz distributed customer lifetime, where the latter distribution is nonmemoryless. This comment corrects an error in their expression for the conditional expected number of individual future purchases [Formula: see text] in a forecasting interval of length [Formula: see text]. Contrary to their approach, the correct derivation of the conditional expectation must be based on the conditional survival and density functions of the lifetime distribution. Using the wrong formula leads managers to overestimate the expected future customer purchases. Further, the comment corrects the erroneous expressions for the conditional variance [Formula: see text] and the conditional mean residual lifetime [Formula: see text].

This paper was accepted by Raphael Thomadsen, marketing.

Supplemental Material: The e-companion is available at https://doi.org/10.1287/mnsc.2022.4422 .
The Practices of Artificial Intelligence Techniques and Their Worth in the Confrontation of COVID-19 Pandemic: A Literature Review
Authors: Mijwil Maad , Al-Mistarehi Abdel-Hameed , Mutar Dhamyaa Salim
Published: April 2022

Today, the medical society is living in the era of artificial intelligence, which is developed and becomes more famous thanks to the coronavirus disease of 2019 (COVID-19) pandemic, which has given the space for artificial intelligence to appear more influential in analyzing medical data and providing very accurate results. This science has deservedly been able to achieve an excellent and vital position among healthcare workers, and it has become a necessary element of their work because of its a great potential for practical decision-making. The prospects of using intelligent systems in the medical field are deemed essential in the health division due to their ability to analyze big data and give exact results, aiming to improve the health of citizens and save their lives. In this article, a set of important information about the vital role of artificial intelligence in the medical field is highlighted. In addition, how this science does manage to confront SARS‐CoV‐2 by highlighting a set of investigations and analyses in predicting the spread of the virus, tracking infections, and diagnosis of cases through chest x-ray images of COVID-19 patients. The database of this article covered more than 40 studies between 2020 and 2021 and investigated the effects of utilizing artificial intelligence techniques in analyzing SARS‐CoV‐2 data. These studies are gathered from PubMed, NCBI, google scholar, Medrxiv, and other sites. This article includes a plethora of information about artificial intelligence and SARS‐CoV‐2. The findings confirm that artificial intelligence has a significant role in the healthcare domain, and it is advised to utilize its applications in the decision-making method.
Challenges and opportunities in delivering multi-institutional and multi-professional research placements
Authors: Ashley Albert , Sutton Emma , MacKinnon Heather , Lotto Robyn
Published: April 2022

This month's instalment of the BANCC column considers the need for alternative models to meet the rising demand for placements and ensure that research is embedded into practice.
How to accurately measure blood pressure
Authors: Jones Kathryn Latimer
Published: April 2022

One very important clinical skill for every veterinary nurse is the accurate measurement of arterial blood pressure in both conscious and anaesthetised patients. These readings are useful for a wide variety of monitoring as well as diagnostic purposes. It is critical to produce accurate results so that patients may receive the best care and treatment as soon as possible. If blood pressure measurement is not performed correctly there is the possibility of an error, which can negatively impact patient management. Blood pressure measurements are sensitive: their accuracy can be affected by the environment the patient is in, the patient's behaviour, measurement procedures, devices used for the measurement and the nurse or clinician carrying out the measurement. To minimise errors in blood pressure measurement, a detailed, standardised measurement protocol is necessary with adequate training. This allows for accurate, repeatable and reliable measurement of blood pressure to be achieved each time.
Active Power Filters in Aircraft Electric Power Systems: A Comparison Among Conventional and Advanced Compensation Techniques
Authors: Khalid Saifullah , Sonia  , Singh Narendra Pratap , Siddiqu Khadim Moin
Published: April 2022

The world is moving towards more electric aircraft due to its benefits for more efficiency and less dependence on conventional energy. However, as conventional energy has its drawback of reduced total energy efficiency for aircraft, the use of more electronics is accountable for higher losses, unbalance currents, reduced power supply performance, and generation of harmonics. In this paper, a comparison among three conventional control techniques (Synchronous Rotating Frame, Sinusoidal Current Control and Constant Instantaneous Power Control) and advanced control techniques (ANN, fuzzy logic controller, genetic algorithm, adaptive blanket body cover algorithm, the combination of ANN & fuzzy logic controller and ANN with the application of genetic & adaptive blanket body search algorithm) for aircraft shunt active power filter has been proposed. Furthermore, the best control schemes for aircraft active power filters will be proposed to depend upon the THD of source current and voltage and the compensation time (speed).
Three-dimensional opto-thermo-mechanical model for predicting photo-thermal optical coherence tomography responses in multilayer geometries
Authors: Salimi Mohammad Hossein , Villiger Martin , Tabatabaei Nima
Published: April 2022

Photothermal optical coherence tomography (PT-OCT) is a functional extension of OCT with the ability to generate qualitative maps of molecular absorptions co-registered with the micron-resolution structural tomograms of OCT. Obtaining refined insight into chemical information from PT-OCT images, however, requires solid understanding of the multifactorial physics behind generation of PT-OCT signals and their dependence on system and sample parameters. Such understanding is needed to decouple the various physical effects involved in the PT-OCT signal to obtain more accurate insight into sample composition. In this work, we propose an analytical model that considers the opto-thermo-mechanical properties of multi-layered samples in 3-D space, eliminating several assumptions that have been limiting previous PT-OCT models. In parametric studies, the model results are compared with experimental signals to investigate the effect of sample and system parameters on the acquired signals. The proposed model and the presented findings open the door for: 1) better understanding of the effects of system parameters and tissue opto-thermo-mechanical properties on experimental signals; 2) informed optimization of experimentation strategies based on sample and system parameters; 3) guidance of downstream signal processing for predicting tissue molecular composition.
Multi-tool optimization for computer controlled optical surfacing
Authors: Ke Xiaolong , Wang Tianyi , Zhang Zili , Huang Lei , Wang Chunjin , Negi Vipender S. , Pullen Weslin C. , Choi Heejoo , Kim Daewook , Idir Mourad
Published: April 2022

With the rapid development of precision technologies, the demand of high-precision optical surfaces has drastically increased. These optical surfaces are mainly fabricated with computer controlled optical surfacing (CCOS). In a CCOS process, a target surface removal profile is achieved by scheduling the dwell time for a set of machine tools. The optimized dwell time should be positive and smooth to ensure convergence to the target while considering CNC dynamics. The total run time of each machine tool is also expected to be balanced to improve the overall processing efficiency. In the past few decades, dwell time optimization for a single machine tool has been extensively developed. While the methods are applicable to multi-tool scenarios, they fail to consider the overall contributions of multiple tools simultaneously. In this paper, we conduct a systematic study on the strategies for multi-tool dwell time optimization and propose an innovative method for simultaneously scheduling dwell time for multiple tools for the first time. First, the influential factors to the positiveness and smoothness of dwell time solutions for a single machine tool are analyzed. The compensation strategies that minimize the residual while considering the CNC dynamics limit are then proposed. Afterwards, these strategies are extended to the proposed multi-tool optimization that further balances the run time of machine tools. Finally, the superiority of each strategy is carefully studied via simulation and experiment. The experiment is performed by bonnet polishing a 60 mm × 60 mm mirror with three tools of different diameters (i.e., 12 mm, 8 mm, and 5 mm). The figure error of the mirror is reduced from 45.42 nm to 11.18 nm root mean square in 13.28 min. Moreover, the measured polishing result well coincides with the estimation, which proves the effectiveness of the proposed method.
Digital-Analog Co-Design for Precision Compressed Integrated Photonic Convolution Neural Network
Authors: Jiang Yue , Zhang Wenjia , He Zuyuan
Published: April 2022

Digital-Analog Co-design for photonic CNN with compressed precision is proposed to answer 3 practical concerns about analog precision: measurement and its mapping to digital domain, minimum demand of physical layer conditions and cheap methods to improve the performance of photonic CNN with poor precision.
Flexible Upstream FEC for Higher Throughput, Efficiency, and Robustness for 50G PON
Authors: Mahadevan Amitkumar , Lefevre Yannick , Harstead Ed , van Hoof Werner , van Veen Doutje , Houtsma Vincent
Published: April 2022

A low-complexity flexible forward error correction scheme based on different shortening and puncturing of the standard G.hsp 50G PON LDPC mother code to achieve enhanced throughput and robustness in upstream PON is motivated and presented.
DeepALM: Holistic Optical Network Monitoring based on Machine Learning
Authors: Cho Joo Yeon , Pedreno-Manresa Jose-Juan , Patri Sai , Abdelli Khouloud , Tropschug Carsten , Zou Jim , Rydlichowski Piotr
Published: April 2022

We demonstrate a machine learning-based optical network monitoring system which can integrate fiber monitoring, predictive maintenance of optical hardware, and security information management in a single solution.
Demonstration of a low latency bandwidth allocation mechanism for mission critical applications in virtual PONs with P4 programmable hardware
Authors: Mafioletti Diego Rossi , Slyne Frank , Giller Robin , O’Hanlon Michael , Coyle David , Ryan Brendan , Ruffini Marco
Published: April 2022

We provide a real-time demonstration of a low-latency PON DBA mechanism, optimised for virtual PONs. Our implementation mixes P4 programmable data plane and software-based virtual DBA to provide efficient fast-track allocation for low latency applications.
Emerging Optical Interconnects for AI Systems
Authors: Ghobadi Manya
Published: April 2022

The ever-growing demand for accurate machine learning models resulted in an increase in dataset and model sizes of deep neural networks. This paper discusses reconfigurable optical networks as the key enabler for scaling AI systems.
Modern applications of total network awareness
Authors: Lindsey Nate , Englund Mark
Published: April 2022

Recent advances in distributed fiber sensing allow new forms of total network awareness and intelligence to be added to layer 1 of optical fiber networks for material improvements in network protection, performance, resilience, and maintenance.
The interdependency of telco- and non-telco networks with a focus on increasing risk and resilience, a new use case for network convergence
Authors: Gladisch Andreas , Düser Michael
Published: April 2022

Convergence happens at different levels, fixed and mobile, smart grids, network sharing. Future risks in interruptions are not only intrinsic to telecommunications networks, but increasingly inter-relate with events in non-telco networks. Resilience concepts need to adapt accordingly. Comments and questions should be directed to the Optica Conference Papers staff (tel: +1 202.416.6191, e-mail: cstech@optica.org).
Extending thermal stability of short-living soliton states in silicon nitride microring resonators
Authors: Grassani D. , El Dirani H. , Sabattoli F. A. , Youssef L. , Petit-Etienne C. , Kerdiles S. , Pargon E. , Liscidini M. , Sciancalepore C. , Bajoni D. , Galli M.
Published: April 2022

Dissipative Kerr solitons in microresonators enable on-chip chip generation of low-noise optical pulse trains with high repetition rates, finding applications in optical communication, distance measurement, spectroscopy and radiofrequency generation. However, the most common photonic integrated platforms often show very short living, hence difficult to achieve, soliton states. Here, we exploit an auxiliary resonance to access soliton regime in Si3N4 microresonators by simple wavelength scanning. We increase the likelihood of single soliton formation by more than two times using backward tuning of the laser, and we show that the increased thermal stability allows soliton formation by thermal tuning of the whole sample, keeping the laser at a fixed frequency.
GSEA–SDBE: A gene selection method for breast cancer classification based on GSEA and analyzing differences in performance metrics
Authors: Ai Hu
Published: April 2022

Motivation

Selecting the most relevant genes for sample classification is a common process in gene expression studies. Moreover, determining the smallest set of relevant genes that can achieve the required classification performance is particularly important in diagnosing cancer and improving treatment.

Results

In this study, I propose a novel method to eliminate irrelevant and redundant genes, and thus determine the smallest set of relevant genes for breast cancer diagnosis. The method is based on random forest models, gene set enrichment analysis (GSEA), and my developed Sort Difference Backward Elimination (SDBE) algorithm; hence, the method is named GSEA–SDBE. Using this method, genes are filtered according to their importance following random forest training and GSEA is used to select genes by core enrichment of Kyoto Encyclopedia of Genes and Genomes pathways that are strongly related to breast cancer. Subsequently, the SDBE algorithm is applied to eliminate redundant genes and identify the most relevant genes for breast cancer diagnosis. In the SDBE algorithm, the differences in the Matthews correlation coefficients (MCCs) of performing random forest models are computed before and after the deletion of each gene to indicate the degree of redundancy of the corresponding deleted gene on the remaining genes during backward elimination. Next, the obtained MCC difference list is divided into two parts from a set position and each part is respectively sorted. By continuously iterating and changing the set position, the most relevant genes are stably assembled on the left side of the gene list, facilitating their identification, and the redundant genes are gathered on the right side of the gene list for easy elimination. A cross-comparison of the SDBE algorithm was performed by respectively computing differences between MCCs and ROC_AUC_score and then respectively using 10-fold classification models, e.g., random forest (RF), support vector machine (SVM), k-nearest neighbor (KNN), extreme gradient boosting (XGBoost), and extremely randomized trees (ExtraTrees). Finally, the classification performance of the proposed method was compared with that of three advanced algorithms for five cancer datasets.

Results showed that analyzing MCC differences and using random forest models was the optimal solution for the SDBE algorithm. Accordingly, three consistently relevant genes (i.e., VEGFD, TSLP, and PKMYT1) were selected for the diagnosis of breast cancer. The performance metrics (MCC and ROC_AUC_score, respectively) of the random forest models based on 10-fold verification reached 95.28% and 98.75%. In addition, survival analysis showed that VEGFD and TSLP could be used to predict the prognosis of patients with breast cancer.

Moreover, the proposed method significantly outperformed the other methods tested as it allowed selecting a smaller number of genes while maintaining the required classification accuracy.
Development of stealth liposomal formulation of celecoxib: In vitro and in vivo evaluation
Authors: Begum M. Yasmin , M. Osmani Riyaz Ali , Alqahtani Ali , Ghazwani Mohammed , Hani Umme , Ather Hissana , Atiya Akhtar , Rahamathulla Mohamed , Siddiqua Ayesha
Published: April 2022

Celecoxib (CLB) is a highly hydrophobic selective cyclo-oxygenase inhibitor with high plasma protein binding and undergoes extensive hepatic metabolism. CLB is highly effective in the treatment of osteo and rheumatoid arthritis as first line therapy but produces severe gastro-intestinal toxicities and cardiovascular side effects. In this research, stealth liposomes of CLB were developed with the intention to reduce the side effects and increase the accumulation of drug in the sites of inflammation. Stealth liposomes were prepared by thin film hydration technique using distearoylphosphatidylcholine and PE-PEG 2000 with variable amounts of cholesterol and characterized. The effects of various lipids such as hydrogenated soy phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearoylphosphatidylcholine and cholesterol content on % drug encapsulation was investigated. The optimized stealth liposomes were characterized by FT-IR and DSC for possible drug excipients interaction. Pharmacokinetics, pharmacodynamics and biodistribution studies were carried out for the stealth liposomes. The results revealed that the stealth liposomes reduced the inflammation to the larger magnitude and have also sustained the magnitude when compared to free drug along with maximum analgesic response. Higher elimination half-life, AUC, MRT and lowered clearance rate denotes the extended bioavailability of the drug in blood. Biodistribution studies revealed that stealth liposomes extend the circulation time of liposomes in blood by decreasing opsonisation and be less concentrated in kidney, thereby reducing the toxicities to RES and renal organs and facilitate the drug accumulation in the area of inflammation. Our results indicated that CLB, without the requirement of modifications to enhance solubilisation, can be encapsulated and released from liposomal formulations. This new-fangled drug delivery approach may be used to circumvent the low bioavailability and toxic side effects of oral CLB formulations.
Sub-micrometer morphology of human atherosclerotic plaque revealed by synchrotron radiation-based μCT—A comparison with histology
Authors: Truong My , Dreier Till , Wassélius Johan , Sundius Lena , Persson Ana , Lovric Goran , Bonnin Anne , Goncalves Isabel , Bech Martin
Published: April 2022

Histology is a long standing and well-established gold standard for pathological characterizations. In recent years however, synchrotron radiation-based micro-computed tomography (SRμCT) has become a tool for extending the imaging of two-dimensional thin sections into three-dimensional imaging of tissue blocks, enabling so-called virtual histology with arbitrary clipping planes, volumetric rendering and automatic segmentation. In this study, we present a thorough characterization of human carotid plaques after endarterectomy of patients with stroke or transient ischemic attack (TIA), investigating several different pathologic structures using both SRμCT and histology. Phase-contrast SRμCT was performed with two different magnifications (voxel sizes 6.5 μm and 0.65 μm, respectively), and histology was performed with multiple different stainings (Alpha-actin, Glycophorin A, von Kossa, Movat, CD68). The 0.65 μm high-resolution SRμCT was performed on selected areas with plaque typical relevant morphology, identified on the 6.5 μm low-resolution SRμCT. The tomography datasets were reconstructed with additional 3D volume rendering and compared to histology. In total, nine different regions with typical pathologic structures were identified and imaged with high-resolution SRμCT. The results show many characteristics typical for advanced atherosclerotic plaques, clinically relevant, namely ruptures with thrombosis, neo-vascularization, inflammatory infiltrates in shoulder regions, lipid rich necrotic cores (LRNC), thin fibrous cap, calcifications, lumen irregularities, and changes in vessel wall structures such as the internal elastic membrane. This method’s non-destructive nature renders details of micro-structures with an excellent visual likeness to histology, with the additional strength of multiplanar and 3D visualization and the possibility of multiple re-scans.
Acute kidney injury in COVID-19 pediatric patients in North America: Analysis of the virtual pediatric systems data
Authors: Raina Rupesh , Mawby Isabelle , Chakraborty Ronith , Sethi Sidharth Kumar , Mathur Kashin , Mahesh Shefali , Forbes Michael
Published: April 2022

Background

Despite extensive research into acute kidney injury (AKI) in adults, research into the epidemiology, associated risk factors, treatment, and mortality of AKI in pediatric COVID-19 patients is understudied. Advancing understanding of this disease is crucial to further developing treatment and preventative care strategies to reduce morbidity and mortality.

Methods

This is a retrospective analysis of 2,546 COVID-19 pediatric patients (age ≤ 21 years) who were admitted the ICU in North America. Analysis of the Virtual Pediatric Systems (VPS) COVID-19 database was conducted between January 1, 2020, and June 30, 2021.

Results

Out of a total of 2,546 COVID positive pediatric patients, 10.8% (n = 274) were diagnosed with AKI. Significantly higher continuous and categorical outcomes in the AKI subset compared to the non-AKI cohort included: length of stay at the hospital (LOS) [9.04 (5.11–16.66) vs. 5.09 (2.58–9.94) days], Pediatric Index of Mortality (PIM) 2 probability of death [1.20 (0.86–3.83) vs. 0.96 (0.79–1.72)], PIM 3 probability of death [0.98 (0.72–2.93) vs. 0.78 (0.69–1.26)], mortality [crude OR (95% CI): 5.01 (2.89–8.70)], airway and respiratory support [1.63 (1.27–2.10)], cardio-respiratory support [3.57 (1.55–8.23)], kidney support [12.52 (5.30–29.58)], and vascular access [4.84 (3.70–6.32)].

Conclusions

This is one of the first large scale studies to analyze AKI among pediatric COVID-19 patients admitted to the ICU in North America. Although the course of the COVID-19 virus appears milder in the pediatric population, renal complications may result, increasing the risk of disease complication and mortality.
Obesity modulates the immune macroenvironment associated with breast cancer development
Authors: Núñez-Ruiz Aleida , Sánchez-Brena Flor , López-Pacheco Cynthia , Acevedo-Domínguez Naray A. , Soldevila Gloria
Published: April 2022

Growing evidence demonstrates a strong correlation between obesity and an increased risk of breast cancer, although the mechanisms involved have not been completely elucidated. Some reports have described a crosstalk between adipocytes, cancer cells, and immune cells within the tumor microenvironment, however, it is currently unknown whether obesity can promote tumor growth by inducing systemic alterations of the immune cell homeostasis in peripheral lymphoid organs and adipose tissue. Here, we used the E0771 breast cancer cell line in a mouse model of diet-induced obesity to analyze the immune subpopulations present in the tumors, visceral adipose tissue (VAT), and spleen of lean and obese mice. Our results showed a significant reduction in the frequency of infiltrating CD8+ T cells and a decreased M1/M2 macrophage ratio, indicative of the compromised anti-tumoral immune response reported in obesity. Despite not finding differences in the percentage or numbers of intratumoral Tregs, phenotypic analysis showed that they were enriched in CD39+, PD-1+ and CCR8+ cells, compared to the draining lymph nodes, confirming the highly immunosuppressive profile of infiltrating Tregs reported in established tumors. Analysis of peripheral T lymphocytes showed that tumor development in obese mice was associated to a significant increase in the percentage of peripheral Tregs, which supports the systemic immunosuppressive effect caused by the tumor. Interestingly, evaluation of immune subpopulations in the VAT showed that the characteristic increase in the M1/M2 macrophage ratio reported in obesity, was completely reversed in tumor-bearing mice, resembling the M2-polarized profile found in the microenvironment of the growing tumor. Importantly, VAT Tregs, which are commonly decreased in obese mice, were significantly increased in the presence of breast tumors and displayed significantly higher levels of Foxp3, indicating a regulatory feedback mechanism triggered by tumor growth. Altogether, our results identify a complex reciprocal relationship between adipocytes, immune cells, and the tumor, which may modulate the immune macroenvironment that promotes breast cancer development in obesity.
Policy search with rare significant events: Choosing the right partner to cooperate with
Authors: Ecoffet Paul , Fontbonne Nicolas , André Jean-Baptiste , Bredeche Nicolas
Published: April 2022

This paper focuses on a class of reinforcement learning problems where significant events are rare and limited to a single positive reward per episode. A typical example is that of an agent who has to choose a partner to cooperate with, while a large number of partners are simplynotinterested in cooperating, regardless of what the agent has to offer. We address this problem in a continuous state and action space with two different kinds of search methods: a gradient policy search method and a direct policy search method using an evolution strategy. We show that when significant events are rare, gradient information is also scarce, making it difficult for policy gradient search methods to find an optimal policy, with or without a deep neural architecture. On the other hand, we show that direct policy search methods are invariant to the rarity of significant events, which is yet another confirmation of the unique role evolutionary algorithms has to play as a reinforcement learning method.