bluuebunny/crossref_metadata_2025 huggingface dataset:
DifferSketching
Authors: Xiao Chufeng , Su Wanchao , Liao Jing , Lian Zhouhui , Song Yi-Zhe , Fu Hongbo
Published: November 2022

Multiple sketch datasets have been proposed to understand how people draw 3D objects. However, such datasets are often of small scale and cover a small set of objects or categories. In addition, these datasets contain freehand sketches mostly from expert users, making it difficult to compare the drawings by expert and novice users, while such comparisons are critical in informing more effective sketch-based interfaces for either user groups. These observations motivate us to analyze how differently people with and without adequate drawing skills sketch 3D objects. We invited 70 novice users and 38 expert users to sketch 136 3D objects, which were presented as 362 images rendered from multiple views. This leads to a new dataset of 3,620 freehand multi-view sketches, which are registered with their corresponding 3D objects under certain views. Our dataset is an order of magnitude larger than the existing datasets. We analyze the collected data at three levels, i.e., sketch-level, stroke-level, and pixel-level, under both spatial and temporal characteristics, and within and across groups of creators. We found that the drawings by professionals and novices show significant differences at stroke-level, both intrinsically and extrinsically. We demonstrate the usefulness of our dataset in two applications: (i) freehand-style sketch synthesis, and (ii) posing it as a potential benchmark for sketch-based 3D reconstruction. Our dataset and code are available at https://chufengxiao.github.io/DifferSketching/.
Efficient Differentiation of Pixel Reconstruction Filters for Path-Space Differentiable Rendering
Authors: Yu Zihan , Zhang Cheng , Nowrouzezahrai Derek , Dong Zhao , Zhao Shuang
Published: November 2022

Pixel reconstruction filters play an important role in physics-based rendering and have been thoroughly studied. In physics-based differentiable rendering, however, the proper treatment of pixel filters remains largely under-explored. We present a new technique to efficiently differentiate pixel reconstruction filters based on the path-space formulation. Specifically, we formulate the pixel
boundary
integral that models discontinuities in pixel filters and introduce new antithetic sampling methods that support differentiable path sampling methods, such as adjoint particle tracing and bidirectional path tracing. We demonstrate both the need and efficacy of antithetic sampling when estimating this integral, and we evaluate its effectiveness across several differentiable- and inverse-rendering settings.
Progressive Simulation for Cloth Quasistatics
Authors: Zhang Jiayi Eris , Dumas Jérémie , Fei Yun (Raymond) , Jacobson Alec , James Doug L. , Kaufman Danny M.
Published: November 2022

The trade-off between speed and fidelity in cloth simulation is a fundamental computational problem in computer graphics and computational design. Coarse cloth models provide the interactive performance required by designers, but they can not be simulated at higher resolutions ("up-resed") without introducing simulation artifacts and/or unpredicted outcomes, such as different folds, wrinkles and drapes. But how can a coarse simulation predict the result of an unconstrained, high-resolution simulation that has not yet been run?

We propose Progressive Cloth Simulation (PCS), a new forward simulation method for efficient
preview
of cloth quasistatics on exceedingly coarse triangle meshes with consistent and progressive improvement over a hierarchy of increasingly higher-resolution models. PCS provides an efficient coarse previewing simulation method that predicts the coarse-scale folds and wrinkles that will be generated by a corresponding converged, high-fidelity C-IPC simulation of the cloth drape's equilibrium. For each preview PCS can generate an increasing-resolution sequence of
consistent
models that progress towards this converged solution. This successive improvement can then be interrupted at any point, for example, whenever design parameters are updated. PCS then ensures feasibility at all resolutions, so that predicted solutions remain intersection-free and capture the complex folding and buckling behaviors of frictionally contacting cloth.
The Continuity of Locomotion
Authors: Freiwald Jann Philipp , Schmidt Susanne , Riecke Bernhard E. , Steinicke Frank
Published: November 2022

Natural interaction between multiple users within a shared virtual environment (VE) relies on each other's awareness of the current position of the interaction partners. This, however, cannot be warranted when users employ noncontinuous locomotion techniques, such as teleportation, which may cause confusion among bystanders.

In this paper, we pursue two approaches to create a pleasant experience for both the moving user and the bystanders observing that movement. First, we will introduce a
Smart Avatar
system that delivers continuous full-body human representations for noncontinuous locomotion in shared virtual reality (VR) spaces.
Smart Avatars
imitate their assigned user's real-world movements when close-by and autonomously navigate to their user when the distance between them exceeds a certain threshold, i.e., after the user teleports. As part of the
Smart Avatar
system, we implemented four avatar transition techniques and compared them to conventional avatar locomotion in a user study, revealing significant positive effects on the observers' spatial awareness, as well as pragmatic and hedonic quality scores.

Second, we introduce the concept of
Stuttered Locomotion
, which can be applied to any continuous locomotion method. By converting a continuous movement into short-interval teleport steps, we provide the merits of non-continuous locomotion for the moving user while observers can easily keep track of their path. Thus, while the experience for observers is similarly positive as with continuous motion, a user study confirmed that
Stuttered Locomotion
can significantly reduce the occurrence of cybersickness symptoms for the moving user, making it an attractive choice for shared VEs. We will discuss the potential of
Smart Avatars
and
Stuttered Locomotion
for shared VR experiences, both when applied individually and in combination.
Assemble Them All
Authors: Tian Yunsheng , Xu Jie , Li Yichen , Luo Jieliang , Sueda Shinjiro , Li Hui , Willis Karl D. D. , Matusik Wojciech
Published: November 2022

Assembly planning is the core of automating product assembly, maintenance, and recycling for modern industrial manufacturing. Despite its importance and long history of research, planning for mechanical assemblies when given the final assembled state remains a challenging problem. This is due to the complexity of dealing with arbitrary 3D shapes and the highly constrained motion required for real-world assemblies. In this work, we propose a novel method to efficiently plan physically plausible assembly motion and sequences for real-world assemblies. Our method leverages the assembly-by-disassembly principle and physics-based simulation to efficiently explore a reduced search space. To evaluate the generality of our method, we define a large-scale dataset consisting of thousands of physically valid industrial assemblies with a variety of assembly motions required. Our experiments on this new benchmark demonstrate we achieve a state-of-the-art success rate and the highest computational efficiency compared to other baseline algorithms. Our method also generalizes to rotational assemblies (e.g., screws and puzzles) and solves 80-part assemblies within several minutes.
A Novel Multi-Constraint Peak Power Prediction Method Combined with Online Model Parameter Identification and State-of-Charge Co-Estimation of Lithium-Ion Batteries
Authors: Qi Chuangshi , Wang Shunli , Cao Wen , Shi Haotian , Xie Yanxin
Published: November 2022

The accuracy of the peak power is influenced by the accurate battery model, the results of the parameter identification, and the state of charge (SOC). First, to accurately predict the peak power of lithium-ion batteries, this paper proposes an improved Thevenin model to describe the operating state of lithium-ion batteries by introducing model noise into the Thevenin model. Second, to achieve accurate online parameter identification, a Forgetting Factor Recursive Extended Least Squares (FFRELS) method is proposed to identify the parameters of the improved model. To optimize the effect of noise on SOC estimation, an improved adaptive extended Kalman filtering (AEKF) algorithm is proposed. Finally, to obtain higher accuracy of peak power estimation, a multi-constrained peak power prediction method based on state-recursive estimation is used in this paper. Experimental results show that the maximum error of the FFRELS algorithm under different working conditions is 34.35 mV, and the SOC estimation error of the improved AEKF algorithm is less than 0.53%. The improved multi-constraint peak power estimation algorithm has high estimation accuracy under two complex working conditions, and can accurately predict the power input and output capability of the battery.
Role of Diethylene Triaminepentaacetic Acid Pentapotassium Salt on Ruthenium CMP in H2O2-Based Slurries
Authors: Ma Huiping , Zhou Jianwei , Wang Chenwei , Zhang Yue , Li Zihao , Zhang Xinying , Liu Guangyao
Published: November 2022

As technology is scaled down to 5 nm or even smaller, ruthenium (Ru) will most likely be chosen as the next generation barrier material for copper interconnects in integrated circuits (ICs). Recently, the higher removal rate of Ru barrier materials in chemical mechanical polishing (CMP) has become a major issue. In this paper, diethylene triaminepentaacetic acid pentapotassium salt (DTPA-5K) was introduced as a new complexing agent in a hydrogen peroxide (H2O2)-based alkaline slurry with the goal of increasing the Ru removal rate (RR) during chemical mechanical polishing (CMP). The synergy of H2O2 and DTPA-5K significantly improved the RR of Ru to 412 Å min−1. Various analytical results, including electrochemical, X-ray photoelectron spectroscopy (XPS), Raman experiments, atomic force microscopy (AFM) and confocal microscope data, revealed that the RR of Ru can be improved by reducing electrostatic repulsion and also by forming Ru-DTPA complexes.
The Utility of Perirenal Fat in Determining the Risk of Onset and Progression of Diabetic Kidney Disease
Authors: Hu Hongtu , Liang Wei , Zhang Zongwei , Liu Zikang , Chu Fan , Bao Yan , Ran Jialu , Ding Guohua
Published: November 2022

Background. Perirenal fat (PRF) has multiple effects on the kidney through its physical structure and adipocytokine-secreting ability. The present study explored the relationship between PRF thickness and the onset and progression of albuminuria in patients with diabetes. Methods. In the cross-sectional analysis, we screened 959 patients from 8764 subjects with type 2 diabetes mellitus (T2DM) who met the inclusion criteria and measured their perirenal fat thickness (PFT) using color Doppler ultrasound. A group of laboratory indexes were included in the analysis models. In a longitudinal study, a total of 218 patients with a baseline UACR <30 mg/g were included in the follow-up study. Results. In a cross-sectional analysis, patients with diabetes and higher PFT presented with higher albuminuria. Multiple logistic regression analysis indicated that PFT was an independent risk factor for the degree of albuminuria in patients with T2DM (odds ratio = 4.186, 95%CI: 2.290–7.653,

P

 < 0.001). In a longitudinal study, 218 albuminuria-free patients with T2DM at the baseline were followed up for a mean of 12.3 months. Based on the cutoff value from the ROC diagnostic test in the cross-sectional study, patients were divided into two groups: higher PFT (H-PFT) and lower PFT (L-PFT). Kaplan–Meier survival curve analysis showed that H-PFT was associated with a higher incidence of albuminuria than L-PFT (log-rank test, χ2 = 4.522,

P

 = 0.033). Cox regression analysis showed that PFT was a risk factor for the earlier onset of albuminuria (hazard ratio 2.83, 95% CI: 1.34–4.88,

P

 < 0.001). Conclusions. PRF evaluated by color Doppler ultrasound is an easy and reliable tool for predicting the onset and progression of albuminuria in patients with T2DM.
Exploring the Mechanism of Action of Trachelospermi Caulis et Folium for Depression Based on Experiments: Combining Network Pharmacology and Molecular Docking
Authors: Wen Lingmiao , Fan Yuqing , Xiong Wei , Liu Yanjun , Zhang Tinglan , Wei Guihua , Altamirano Alvin , Zhang Tian-e , Yan Zhiyong
Published: November 2022

Objective. To reveal the safety, efficacy, and mechanism of action of Trachelospermi Caulis et Folium (TCEF) for treating depression. Methods. The maximum dose method was employed to evaluate the safety of TCEF, and its antidepressant activity was assessed using the tail suspension and sugar water depletion tests. The main components of TCEF were determined using ultrahigh performance liquid chromatography coupled with quadrupole exactive orbitrap mass spectrometer (UHPLC-Q-EOMS). The active ingredients and their action targets were obtained using network pharmacology with SwissADME and SwissTargetPrediction screening, and the targets of depression were obtained using GeneCards, DrugBank, etc. The drug and depression-related targets were intersected and analyzed via PPI network, GO, and KEGG. Subsequently, the binding ability of the core components of TCEF to the core targets was validated via molecular docking and simulation. Results. No statistically significant difference was observed between the normal and TCEF groups in terms of body weight, visceral index, and biochemical parameters (

P
>
0.05

). Compared with the model group, all dose groups of TCEF had reduced the immobility time of tail suspension (

P
<
0.05

) and increased the rate of sugar water consumption (

P
<
0.05

). UHPLC-Q-EOMS was employed to identify 59 major components of TCEF, and network pharmacology analysis was used to screen 48 active components of TCEF for treating depression, corresponding to 139 relevant targets, including ALB, AKT1, TNF, ESR1, and CTNNB1. The involved pathways include neuroactive ligand-receptor interaction. The molecular docking results indicated that the core components have a good binding activity to the core targets. Conclusions. TCEF is a relatively safe antidepressant medicine that exerts therapeutic effects through multiple components, targets, and pathways, providing a new idea and theoretical basis for future use of TCEF to treat depression.
DSOQR: Deep Reinforcement Learning for Online QoS Routing in SDN-Based Networks
Authors: Zhang Lianming , Lu Yong , Zhang Dian , Cheng Haoran , Dong Pingping
Published: November 2022

With the rapid development of mobile communication technology, there are an increasing number of new network applications and services, and the existing best-effort routing algorithms cannot meet the quality-of-service (QoS) requirements of these applications and services. QoS-routing optimization solutions based on a software-defined network (SDN) are often targeted at specific network scenarios and difficult to adapt to changing business requirements. The current routing algorithms based on machine learning (ML) methods can generally only handle discrete, low-dimensional action spaces and use offline network data for training, which is not effective for dynamic network environments. In this study, we propose DSOQR, which is an online QoS-routing framework based on deep reinforcement learning (DRL) and SDN. DSOQR collects network status information in real time through the software-defined paradigm and carries out on-policy learning. Under this framework, we further propose SA3CR, which is a QoS-routing algorithm based on SDN and asynchronous advantage actor-critic (A3C). The SA3CR algorithm can dynamically switch routing paths that meet the conditions according to the current network status and the needs of different service types to ensure the QoS of target traffic. Experimental results show that DSOQR is effective and that the SA3CR algorithm has better performance in terms of delay, throughput, and packet loss rate.
Breast Cancer Exosome-Derived miR-425-5p Induces Cancer-Associated Fibroblast-Like Properties in Human Mammary Fibroblasts by TGFβ1/ROS Signaling Pathway
Authors: Zhu Yue , Dou He , Liu Yuqi , Yu Pingyang , Li Fucheng , Wang Youyu , Xiao Min
Published: November 2022

The connection between the cellular microenvironment and tumor cells is crucial for tumor progression. However, the process by which normal fibroblasts (NFs) become cancer-associated fibroblasts (CAFs) is unknown, and mounting evidence suggests that some microRNAs (miRNAs) have an important role in converting NFs into CAFs. Breast cancer (BC) has been proven to have enhanced miR-425-5p expression in order to support progression. We discovered that human mammary fibroblasts (HMFs) could uptake BC cell line-derived exosomes to change their properties, promoting the switch to the CAF phenotype and increasing cell motility, as evidenced by an increase in CAF activation-related marker protein expression and cell proliferation, invasion, and migration. Transfection of exosomes is obtained from BC cells, and miR-425-5p inhibitors suppressed the aforementioned effects as well as lowered chemokine levels and gene expression related with proliferation and metastasis. By suppressing the expression of its target gene TGFβRII (TGFβ1 receptor), miR-425-5p enhanced the transition of HMFs to the CAF phenotype. MDA-MB-231 cells and CAFs stimulated by HMF absorption of MDA-MB-23-derived exosomes showed similar proliferation, invasion, migration, and expression of -SMA, FAP, CXCL1, IL-6, TGFβ1, P21, P27, Ki67, vimentin, E-cadherin, N-cadherin, α-catenin, fibronectin, and MMP-2. TGFβ1 overexpression enhanced ROS production. Finally, we found that HMFs transiently transfected with miR-425-5p can promote tumor growth in vivo. Finally, these findings provide fresh insight on miR-425-5p as an important mediator of the interaction between BC cells and stroma.
Security Enhancement of Power Systems through Interline Power Flow Controller (IPFC) under Contingency Condition: A Case Study and Analysis‐EEP 400 kV System
Authors: Woldesemayat Muluneh Lemma , Tantu Ashenafi Tesfaye
Published: November 2022

Increasing contingency issues result in inevitable bus voltage violations and force the system to operate around its limit. This situation creates strains that are faced by the security of the Ethiopian Electric Power (EEP) 400 kV system. In this paper, the static security assessment (SSA) of the system under the base and N-1 contingency scenarios was examined by using Newton-Raphson (NR) method. The Bus and line loading-based composite severity indices (CSI) were utilized to determine the state of the system and to get an optimal location for interline power flow controller (IPFC) placement. In this research, the optimal sizing of IPFC was done by using Grey Wolf Optimization (GWO) algorithm. From N-1 contingency analysis, Gelan to Sebeta and Gelan to Holeta branches were found as optimal places for IPFC placement. The IPFC optimal parameters were the series voltage and angle injection found as Vse1 = 0.1101pu, Vse2=0.1096pu, δse1=-0.1848rad, and δse2=2.7682rad with the optimal size of 50 MVA for each IPFC. The average bus voltage severity index (BVSI) without and with IPFC cases was found as 217.243% and 2.641% respectively. The average line severity index (LSI) without and with IPFC cases were found as 39.448% and 15.283% respectively. Moreover, the total line loss under severe N-1 contingency scenarios without and with IPFC integration was 437.783 MW and 63.136 MW respectively. From analysis, it was observed and concluded that the static security of the EEP 400 kV system under N-1 contingency conditions is effectively improved by the integration of IPFC.
Comparative Study of the Immune Response Induced by an Argentinian Classical Strain of IBDV in Two Chicken Breeds
Authors: Jaton Juan , Lucero María Soledad , Richetta Matías , Pinto Silvina , Gravisaco María José , Berinstein Analía , Gómez Evangelina , Chimeno Zoth Silvina
Published: November 2022

The hybrid chicken Negra INTA, which originated at the National Institute of Agricultural Technology (INTA), is the product of the cross between Barred Plymouth Rock females and Rhode Island Red males, and it is used as a laying hen for egg consumption. It has been characterized by productive parameters, but the characterization from an immunological perspective has not been done yet. Infectious bursal disease virus (IBDV) causes a highly contagious viral disease that affects the bursa of Fabricius. Although most chickens are regularly vaccinated against IBDV, this virus still generates negative impacts on production with significant economic losses. The aim of the present work was to compare the immune responses of the Negra INTA hybrid and the White Leghorn layer line to the infection with a field isolate of IBDV. Four-week-old chickens were infected with a single dose of IBDV and at 3, 5, 7, and 30 days postinfection (dpi), bursae were removed, and different parameters were evaluated. Results showed that the reduction of the bursa body (BB) ratio and the histopathological damage were maximum on day 7 postinfection (pi). The viral load was greater in the hybrid Negra INTA at 5 dpi. The humoral immune response between both breeds was similar, although more animals from the commercial line showed higher titers of neutralizing antibodies. Flow cytometry analysis revealed that Bu+ bursal lymphocytes reached a minimum at 7 dpi. Meanwhile, T cell infiltration measured by the percentage of CD3+, CD4+, and CD8+ cells in the bursa was at its maximum at 5 dpi. To our knowledge, this work describes for the first time the pathogenesis and the immune response caused by an Argentinian IBDV isolate in two different chicken lines.
Mortality Rate and Years of Life Lost due to Hypertension in the South of Iran between 2004 and 2019: A Population-Based Study
Authors: Mirahmadizadeh Alireza , Vali Mohebat , Hassanzadeh Jafar , Dehghani Seyed Parsa , Razeghi Ahmadreza , Azarbakhsh Habibollah
Published: November 2022

Introduction. Hypertension is known worldwide as a preventable significant risk factor for cardiovascular diseases and their mortality. This study was designed to determine the mortality rate and years of life lost (YLL) due to hypertension in Fars Province. Method. In this cross-sectional study, we extracted all death reports due to hypertension based on age, gender, and the year of death based on ICD-10 from the EDRS system (Electronic Death Registration System). The YLL analysis due to premature death related to hypertension was executed by the 2015 YLL template from WHO in EXCEL 2016 software. To examine the trend of crude and standardized mortality rates and YLL rates for different years, joinpoint regression was used based on the log-linear model. Results. In the 16 years that the study was done (2004–2019), 13443 death cases occurred in the Fars Province, 51.0% of which (6859 cases) were in females and 48.5% (6515 cases) of which were in the 80+ age group. Total YLL due to hypertension in these 16 years of study was 61,344 (1.9 per 1000) in males, 64,903 (2.1 per 1000) in females, and 126,247 (2.0 in 1000) in both genders. According to the joinpoint regression analysis, the 16-year trend of YLL rate due to premature mortality was increasing: the average annual percent change (AAPC) was 4.9% (95% CI −2.6 to 12.85,

p
 
v
a
l
u
e
=
0.205

) for males and 8.4% (95% CI 5.2 to 11.7,

p

value <0.001) for females. Conclusion. Considering the increasing trend in crude and standardized mortality rates and YLL due to hypertension, it is important for policymakers and decision makers of Health Policy Centers to promote and inform people about the importance of hypertension control and to familiarize them with proper, preventive interventions such as the importance of a healthy diet, routine physical activity, and routine learning programs for different groups in the society especially for people at a higher risk of hypertension.
Spatial and Temporal Trends in the Timing of Budburst for Australian Wine Regions
Authors: Liles C. , Verdon-Kidd D. C.
Published: November 2022

Background and Aims. This research investigates spatial and temporal trends in budburst timing across Australian wine regions from 1910–2019. The potential drivers of these observed trends were then identified, including anthropogenic climate change and large-scale climate drivers (El Nino–Southern Oscillation (ENSO), Indian Ocean Dipole (IOD), and Southern Annular Mode (SAM)). Methods and Results. The timing of budburst was approximated using accumulation measurements applied to Australia wide gridded temperature data. We show that the modelled budburst date has been gradually shifting to earlier in the year for most (95%) Australian wine regions, at an average rate of one day every 24 years. This linear trend in budburst timing is likely to be associated with steadily increasing air temperatures due to anthropogenic climate change. Significant interannual variability was also observed and was correlated with IOD and SAM; however, no significant relationship was found with ENSO. Positive IOD phases result in budburst occurring on average four days earlier than the long-term average; however, this can be as high as eight days. Conclusions. The results of this study highlight that budburst timing for wine grapes is not a stationary phenomenon and is influenced by both natural and anthropogenic conditions. Significance of the Study. Understanding variability and trends in modelled budburst timing will assist tactical and strategic management practices and improve phenological modelling and adaptation planning for climate change.
Quizlet as a Learning Tool for Enhancing L2 Learners’ Lexical Retention: Should It be Used in Class or at Home?
Authors: Nguyen Long Quoc , Le Ha Van
Published: November 2022

In the twenty-first century, with the evolution of technologies, teaching and learning practices, especially in second language acquisition, have taken a significant leap. Numerous applications and software have been created to facilitate and boost learners’ L2 vocabulary. The goal of this study is to examine the effectiveness of Quizlet in enhancing lexical retention of EFL students at a private institution in Vietnam in two learning modes: at home and in class. Eighty-nine university students participated in the study and were separated into three groups. While the in-class group (n=31) had weekly sessions of vocabulary revision in class with their teacher, the at-home group (n=30) did the weekly reviews on Quizlet at home by themselves. The control group (n=28), however, did not utilize Quizlet for vocabulary review either in class or at home. During four weeks, the three groups learned and practiced 32 target words, divided into four sets (1 set=8 items), with each set utilized in one week. Via a quasi-experimental design including a pretest and a posttest, the quantitative data were analyzed with the employment of the Generalized Linear Mixed Model to generate reliable outcomes. Semistructured interviews were conducted after the posttest to gain insights into learners’ opinions on Quizlet use. The results indicated that Quizlet was effective in boosting lexical gains in second language acquisition and that most participants were interested in interacting with this tool for reviewing vocabulary. However, there was no statistically significant difference in lexical gains between the at-home and in-class groups. Pedagogical implications, as well as recommendations for future research, were also discussed.
Epileptic Seizure Detection Using a Hybrid 1D CNN-Machine Learning Approach from EEG Data
Authors: Hassan Fatima , Hussain Syed Fawad , Qaisar Saeed Mian
Published: November 2022

Electroencephalography (EEG) is a widely used technique for the detection of epileptic seizures. It can be recorded in a noninvasive manner to present the electrical activity of the brain. The visual inspection of nonlinear and highly complex EEG signals is both costly and time-consuming. Therefore, an effective automatic detection system is needed to assist in the long-term evaluation and treatment of patients. Traditional approaches based on machine learning require feature extraction, while deep learning approaches are time-consuming and require more layers for effective feature learning and processing of complex EEG waveforms. Deep learning-based approaches also have weak generalization ability. This paper proposes a solution based on the combination of convolution neural networks (CNN) and machine learning classifiers. It preprocesses the EEG signal using the Butterworth filter and performs feature extraction using CNN. From the extracted set of features, the approach selects only the relevant features using mutual information-based estimators to reduce the curse of dimensionality and improve classification accuracy. The selected features are then passed as input to different machine learning classifiers. The suggested solution is evaluated on the University of Bonn dataset and CHB-MIT datasets. Our model effectively predicts 2, 3, 4, and 5 classes with accuracy of 100%, 99%, 94.6%, and 94%, respectively, for the Bonn dataset and 98% for CHB-MIT datasets.
The Crossroads of Cancer Epigenetics and Immune Checkpoint Therapy
Authors: Micevic Goran , Bosenberg Marcus W. , Yan Qin
Published: November 2022

Immune checkpoint inhibitors (ICI) have significantly improved treatment outcomes for several types of cancer over the past decade, but significant challenges that limit wider effectiveness of current immunotherapies remain to be addressed. Certain “cold” tumor types, such as pancreatic cancer, exhibit very low response rates to ICI due to intrinsically low immunogenicity. In addition, many patients who initially respond to ICI lack a sustained response due to T-cell exhaustion. Several recent studies show that epigenetic modifiers, such as SETDB1 and LSD1, can play critical roles in regulating both tumor cell–intrinsic immunity and T-cell exhaustion. Here, we review the evidence showing that multiple epigenetic regulators silence the expression of endogenous antigens, and their loss induces viral mimicry responses bolstering the response of “cold” tumors to ICI in preclinical models. Similarly, a previously unappreciated role for epigenetic enzymes is emerging in the establishment and maintenance of stem-like T-cell populations that are critical mediators of response to ICI. Targeting the crossroads of epigenetics and immune checkpoint therapy has tremendous potential to improve antitumor immune responses and herald the next generation of sustained responses in immuno-oncology.
Gallium-68–labeled Peptide PET Quantifies Tumor Exposure of PD-L1 Therapeutics
Authors: Mishra Akhilesh , Kumar Dhiraj , Gupta Kuldeep , Lofland Gabriela , Sharma Ajay Kumar , Banka Dhanush S. , Hobbs Robert F. , Dannals Robert F. , Rowe Steven P. , Gabrielson Edward , Nimmagadda Sridhar
Published: November 2022

Purpose:

Immune checkpoint therapy (ICT) is currently ineffective in a majority of patients. Tumor drug exposure measurements can provide vital insights into mechanisms involved in the resistance of solid tumors to those therapeutics; however, tools to quantify in situ drug exposure are few. We have investigated the potential of programmed death-ligand 1 (PD-L1) pharmacodynamics, quantified using PET, to inform on the tumor exposure of anti–PD-L1 (aPD-L1) therapeutics.

Experimental Design:

To noninvasively quantify PD-L1 levels, we first developed a novel peptide-based gallium-68–labeled binder, [68Ga]Ga-DK223, and evaluated its in vivo distribution, pharmacokinetics, and PD-L1 specificity in preclinical models of triple-negative breast cancer and urothelial carcinoma with variable PD-L1 expression. We then quantified baseline and accessible PD-L1 levels in tumors as a noninvasive pharmacodynamic measure to assess tumor exposure to two aPD-L1 antibodies (avelumab and durvalumab).

Results:

DK223 exhibited a KD of 1.01±0.83 nmol/L for PD-L1 and inhibited the PD-1:PD-L1 interaction in a dose-dependent manner. [68Ga]Ga-DK223 provides high-contrast PET images within 60 minutes of administration and detects PD-L1 in an expression-dependent manner in xenograft models. PD-L1 pharmacodynamics measured using [68Ga]Ga-DK223-PET revealed that avelumab and durvalumab had similar exposure early during therapy, but only durvalumab exhibited sustained exposure at the tumor.

Conclusions:

[68Ga]Ga-DK223 detected variable PD-L1 levels and exhibited salient features required for clinical translation. [68Ga]Ga-DK223-PET could be useful for quantifying total PD-L1 levels at baseline and accessible PD-L1 levels during therapy to understand drug exposure at the tumor, thus supporting its use for guiding and optimizing ICT.
Dynamic Mutational Landscape of Cerebrospinal Fluid Circulating Tumor DNA and Predictors of Survival after Proton Craniospinal Irradiation for Leptomeningeal Metastases
Authors: Wijetunga N. Ari , Goglia Alexander G. , Weinhold Nils , Berger Michael F. , Cislo Michael , Higginson Daniel S. , Chabot Kiana , Osman Ahmed M. , Schaff Lauren , Pentsova Elena , Miller Alexandra M. , Powell Simon N. , Boire Adrienne , Yang Jonathan T.
Published: November 2022

Purpose:

Proton craniospinal irradiation (pCSI) is a promising treatment for patients with solid tumor leptomeningeal metastasis (LM). We hypothesize that genetic characteristics before and changes resulting after pCSI will reflect clinical response to pCSI. We analyzed the cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) from patients receiving pCSI for LM and explored genetic variations associated with response.

Experimental Design:

We subjected CSF from 14 patients with LM before and after pCSI to cell-free DNA sequencing using a targeted-sequencing panel. In parallel, plasma ctDNA and primary tumors were subjected to targeted sequencing. Variant allele frequency (VAF) and cancer cell fraction (CCF) were calculated; clonality of observed mutations was determined. Kaplan–Meier analysis was used to associate genomic changes with survival.

Results:

The median overall survival (OS) for the cohort was 9 months [interquartile range (IQR), 5–21 months]. We showed clonal evolution between tumor and ctDNA of the CSF and plasma with unique mutations identified by compartment. Higher CSF ctDNA mean VAF before pCSI (VAFpre) had worse OS (6 months for VAFpre ≥ 0.32 vs. 9 months for VAFpre < 0.32; P = 0.05). Similarly, increased VAF after pCSI portended worse survival (6 vs. 18 months; P = 0.008). Higher mean CCF of subclonal mutations appearing after pCSI was associated with worse OS (8 vs. 17 months; P = 0.05).

Conclusions:

In patients with solid tumor LM undergoing pCSI, we found unique genomic profiles associated with pCSI through CSF ctDNA analyses. Patients with reduced genomic diversity within the leptomeningeal compartment demonstrated improved OS after pCSI suggesting that CSF ctDNA analysis may have use in predicting pCSI response.
History of the Thyroid
Authors: Connelly Kara J. , Park Julie J. , LaFranchi Stephen H.
Published: November 2022

The history of the thyroid dates from 2697 BCE when the “Yellow Emperor” Hung Ti described the use of seaweed to treat goiter. The English name “thyroid” was coined by Thomas Wharton in 1656 from the Greek word for a shield. Bernard Courtois discovered iodine in 1811 when he noted a residual purplish ash while burning seaweed. Robert Graves is known for his classic 1835 report of “palpitations, goiter, and exophthalmos” in three women, but Caleb Parry observed the same clinical features in 1786. The clinical syndrome we now recognize as hypothyroidism was characterized as “myxoedema” in 1878 by William Ord at St. Thomas Hospital. In 1891, George Murray reported that injection of thyroid extract from sheep led to improvement in symptoms in a woman with myxedema. Thomas Kocher, who reported that patients with goiter who underwent complete thyroidectomy developed cachexia strumipriva, was awarded the Nobel Prize in Physiology and Medicine in 1909. Edward Kendall discovered “thyroxin” on Christmas day in 1914. Studies by David Marine that iodine treatment prevented endemic goiter led to salt iodination, which has largely eradicated endemic cretinism. In 1973, Jean Dussault reported detection of congenital hypothyroidism by screening newborn populations.
The Long Path to Our Current Understanding Regarding Care of Children with Differences/Disorders of Sexual Development
Authors: Witchel Selma F. , Mazur Tom , Houk Christopher P. , Lee Peter A.
Published: November 2022

Testes were associated with maleness from antiquity, and ancient societies had fanciful myths about the origins of the sexes and about fetal sexual development. 17th century anatomists developed the concept that mammals developed from eggs and discovered sperm in semen; in 1878, Hertwig observed sperm entering eggs (of sea urchins), establishing the cellular basis of sex development. Individuals with atypical genitalia were known clinically in the 17th century, with much debate about their origins, but by the late 19th century it was generally accepted that gonads determined sex, and that sex determined gender role. Testosterone was isolated in 1935, and Alfred Jost showed that both circulating testosterone and diffusible anti-Mullerian hormone were needed for male development. Patients with apparent androgen insensitivity were reported in 1937 and shown to be unresponsive to exogenous androgen by Lawson Wilkins in 1957; androgen receptor mutations were reported in 1989. Steroidogenic errors were associated with differences in sex development (DSDs) starting in the 1940s, and finding mutations in the responsible enzymes explained many forms of hyper- and hypo-androgenism in both sexes. Sex chromosomes were identified in the early 20th century; Y was associated with maleness, and the responsible SRY gene was identified in 1991. Early efforts to manage patients with DSDs were confounded by philosophical perspectives on the relative roles of prenatal biology versus postnatal environment. Approaches to natal sex assignment evolved in the later 20th century and now emphasize a team approach based on data, not guessing, parental involvement, cultural considerations, and the acknowledgement of uncertainty.
Endoscopic Approach to Duodenal Adenomas in Familial Adenomatous Polyposis: A Retrospective Cohort
Authors: Lemos Garcia Joana , Rosa Isadora , Pereira da Silva João , Lage Pedro , Claro Isabel
Published: November 2022

Introduction: Over 90% of the patients with familial adenomatous polyposis (FAP) will develop duodenal adenomas. Aim: The aim of this study was to evaluate the effectiveness and safety of endoscopic excision of large duodenal adenomas in FAP patients. Methods: All FAP patients from a familial risk clinic submitted to endoscopic therapy for duodenal adenomas ≥10 mm between January 2010 and February 2021 were included. Results: From 151 FAP families, 22 patients (50 lesions) were included: 54.5% female; median follow-up 8.5 (IQR: 5.8–12.3) years after the first endoscopy. First therapeutic endoscopy occurred at a median age of 41.0 years (IQR: 33.0–58.2). Repeat therapeutic endoscopy was required in 54.5% of patients. Median size of the largest adenoma was 15 mm (IQR: 10–18 mm); resection was piecemeal in 63.1% and en bloc in the remaining. In 2 cases, the resection was incomplete (fibrosis due to previous resection and difficult positioning). Complications occurred in 6.3% of the resected lesions (4 patients): 2 immediate (bleeding, perforation); 4 in the first week (1 bleeding, 2 mild pancreatitis, 1 perforation requiring surgery; the latter two after ampullectomy). Histology revealed low-grade dysplasia adenomas in 90.1%; no adenocarcinomas were found. One patient with Spigelman stage IV disease not amenable to endoscopic control underwent elective duodenopancreatectomy (without duodenal cancer). Conclusion: Endoscopic surveillance and treatment of duodenal adenomas in FAP patients was safe and effective in the prevention of duodenal cancer.
Dupilumab-Induced Lichen Planus: A Case with Oral and Cutaneous Eruptions
Authors: Kern Laura , Kleinheinrich Luisa , Feldmann Robert , Sator Paul , Stella Alexander , Breier Friedrich
Published: November 2022

Lichen planus is a chronic, inflammatory, immune-mediated dermatosis affecting the patient’s skin, scalp, mucous membranes, and nails. Drug-induced lichen planus is described after the administration of antimalarials, ß-blockers, methyldopa, NSAIDs, penicillamines, and sodium aurothiomalate. The use of biologicals such as adalimumab, etanercept, and infliximab has also been linked with the appearance of lichenoid eruptions in the recent past. In this case, we report on a patient developing oral and cutaneous lichen planus after the administration of dupilumab. The lichenoid lesions occurred after 11 months of the drug’s administration and involved the buccal walls, trunk, and extremities. Dupilumab had been administered in an effort to counter severe atopic dermatitis exacerbations. Dupilumab is associated with a downregulation of T-helper 2 cell activation by blocking the Interleukin-4/Interleukin-13 pathway, so leading to a TH1/TH2 imbalance. This imbalance may cause a shift toward a TH1-mediated immune response and be an explanation for the drug-induced lichen planus. Dupilumab was discontinued, and the patient was treated with oral corticosteroids and UVB phototherapy, leading to a significant improvement in the lichen planus lesions.
Loss of Pten in Renal Tubular Cells Leads to Water Retention by Upregulating AQP2
Authors: Sun Zhuo , Shao Xiaotong , Wu Haotian , Zhao Yaxian , Cao Yidan , Li Danhua , Sun Ying , Wang Qingling
Published: November 2022

Introduction: Phosphatase and tensin (PTEN) is a multifunctional gene associated with the normal development and physiological function of various tissues including the kidney. However, its role in renal tubular reabsorption function has not been well elucidated. Methods: We generated a renal tubule-specific Pten knockout mouse model by crossing Ptenfl/fl mice with Ksp-Cre transgenic mice, evaluated the effect of Pten loss on renal tubular function, and investigated the underlying mechanisms. Results: Pten loss resulted in abnormal renal structure and function and water retention in multiple organs. Our results also demonstrated that aquaporin-2 (AQP2), an important water channel protein, was upregulated and concentrated on the apical plasma membrane of collecting duct cells, which could be responsible for the impaired water balance in Pten loss mice. The regulation of Pten loss on AQP2 was mediated by protein kinase B (AKT) activation. Conclusions: Our results reveal a connection between PTEN gene inactivation and water retention, suggesting the importance of PTEN in normal kidney development and function.
Larvasida, Daun Jeruk, Demam Ber Pembuatan Larvasida Daun Jeruk Limau Dan Kelambu Air Untuk Pencegahan Kasus Demam Berdarah Karang Joang
Authors: Ernawati Lusi
Published: November 2022

Dinas Kesehatan Balikpapan masih mencatat angka kasus DBD hingga pekan ketiga Maret tahun 2022 sedikitnya ada 90 kasus. Pada masa pandemi saat ini, hampir semua orang berfokus pada pencegahan dan perawatan infeksi Covid-19. Seperti yang telah diketahui, penyakit DBD juga tidak kalah pentingnya untuk diwaspadai dan diperhatikan, mengingat DBD masih menjadi penyakit menular berbahaya di Indonesia. Berbagai upaya telah dilakukan untuk mencegah dan menanggulangi DBD, seperti penggunaan larvasida. Hanya saja nyamuk DBD sudah mulai rentan dengan larvasida kimia yang selama ini sering digunakan oleh masyarakat. Tujuan kegiatan pengabdian kepada masyarakat ini memberikan pelatihan pembuatan larvasida alami dari bahan daun jeruk limau (citrus aurantifolia) yang lebih ramah lingkungan. Pelaksanaan diawali dengan pemberian sosialisasi, pelatihan pembuatan larvasida kepada masyarakat, dan evaluasi pengetahuan. Pelaksanaan pengabdian dilakukan di masyarakat Karang Joang, Balikpapan Utara. Metode pelaksanaan dilakukan dengan sesi ceramah dan tanya jawab dari masyarakat. Pelaksanaan pelatihan pembuatan larvasida dilakukan secara langsung dengan menerapkan protokol kesehatan. Selain memberikan edukasi dan pelatihan inovasi pembuatan larvasida alami, pembuatan kelambu air di beberapa penampungan air milik warga dan sosialisasi serupa dengan melibatkan kader Jumantik (Juru Pemantau Jentik) juga dilakukan.
Penyuluhan Tanda Bahaya Kehamilan Trimester I di Dusun Uraur Nuduasiwa Kecamatan Kairatu Kabupaten Seram Bagian Barat Provinsi Maluku 2021
Authors: Mayasari Windatania
Published: November 2022

Salah satu penyebab masih tingginya Angka Kematian Ibu adalah keterlambatan pertolongan kasus kegawatdaruratan maternal. Keterlambatan itu terjadi karena pengetahuan ibu yang kurang terhadap tanda bahaya kehamilan. Tanda bahaya kehamilan dapat terjadi pada trimester I, trimester II dan trimester III. Tujuan pengabdian kepada masyarakat untuk meningkatkan pemahaman dan peningkatan pengetahuan tentang tanda bahaya kehamilan pada trimester I. Metode yang digunakan adalah dengan memberikan penyuluhan tanda bahaya kehamilan trimester I. Sasaran pada kegiatan ini adalah seluruh ibu hamil trimester I. Responden dalam kegiatan ini sebanyak 20 orang di Dusun Uraur Nuduasiwa Kecamatan Kairatu Kabupaten Seram Bagian Barat Provinsi Maluku. Pengabdian kepada Masyarakat dilakukan pada bulan Juli 2021. Penyampaian Informasi melalui metode ceramah dan tanya jawab. Gambaran pengetahuan responden pada kegiatan ini dapat terlihat saat melakukan tanya jawab tentang tanda bahaya kehamilan trimester I. Peningkatan pengetahuan terlihat dari hasil pre test 5 orang (25%) kategori baik, setelah dilakukan penyuluhan ada peningkatan pengetahuan sebesar 90%. Kesimpulan yang didapat yaitu ada peningkatan pengetahuan tanda bahaya kehamilan trimester I di Dusun Uraur Nuduasiwa Kecamatan Kairatu Kabupaten Seram Bagian Barat Provinsi Maluku.