bluuebunny/crossref_metadata_2025 huggingface dataset:
Addressing resistance to PD-1/PD-(L)1 pathway inhibition: considerations for combinatorial clinical trial designs
Authors: Zhang Tian , Forde Patrick M , Sullivan Ryan J , Sharon Elad , Barksdale Elizabeth , Selig Wendy , Ebbinghaus Scot , Fusaro Gina , Gunenc Damla , Battle Dena , Burns Robyn , Hurlbert Marc S , Stewart Mark , Atkins Michael B
Published: May 2023

With multiple PD-(L)1 inhibitors approved across dozens of indications by the US Food and Drug Administration, the number of patients exposed to these agents in adjuvant, first-line metastatic, second-line metastatic, and refractory treatment settings is increasing rapidly. Although some patients will experience durable benefit, many have either no clinical response or see their disease progress following an initial response to therapy. There is a significant need to identify therapeutic approaches to overcome resistance and confer clinical benefits for these patients. PD-1 pathway blockade has the longest history of use in melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). Therefore, these settings also have the most extensive clinical experience with resistance. In 2021, six non-profit organizations representing patients with these diseases undertook a year-long effort, culminating in a 2-day workshop (including academic, industry, and regulatory participants) to understand the challenges associated with developing effective therapies for patients previously exposed to anti-PD-(L)1 agents and outline recommendations for designing clinical trials in this setting. This manuscript presents key discussion themes and positions reached through this effort, with a specific focus on the topics of eligibility criteria, comparators, and endpoints, as well as tumor-specific trial design options for combination therapies designed to treat patients with melanoma, NSCLC, or RCC after prior PD-(L)1 pathway blockade.
Unconditional access to non-invasive prenatal testing (NIPT) for adult-onset conditions: a defence
Authors: Marks India R , Mills Catherine , Devolder Katrien
Published: May 2023

Over the past decade, non-invasive prenatal testing (NIPT) has been adopted into routine obstetric care to screen for fetal sex, trisomies 21, 18 and 13, sex chromosome aneuploidies and fetal sex determination. It is predicted that the scope of NIPT will be expanded in the future, including screening for adult-onset conditions (AOCs). Some ethicists have proposed that using NIPT to detect severe autosomal AOCs that cannot be prevented or treated, such as Huntington’s disease, should only be offered to prospective parents who intend to terminate a pregnancy in the case of a positive result. We refer to this as the ‘conditional access model’ (CAM) for NIPT. We argue against CAM for NIPT to screen for Huntington’s disease or any other AOC. Next, we present results from a study we conducted in Australia that explored NIPT users’ attitudes regarding CAM in the context of NIPT for AOCs. We found that, despite overall support for NIPT for AOCs, most participants were not in favour of CAM for both preventable and non-preventable AOCs. Our findings are discussed in relation to our initial theoretical ethical theory and with other comparable empirical studies. We conclude that an ‘unconditional access model’ (UAM), which provides unrestricted access to NIPT for AOCs, is a morally preferable alternative that avoids both CAM’s fundamental practical limitations and the limitations it places on parents’ reproductive autonomy.
Leadership and resilience: a viewpoint of Ukrainian doctors
Authors: Diakunchak Yaroslav , Bazylevych Andrii , Vynnyk Olesya , Zhurayev Rustam
Published: May 2023

Over the 1 year and 3 months, Ukrainian people, and especially Ukrainian medical community, keep resilience in this awful full-scale Russian invasion of our country. Due to our brave defenders, Ukrainian Armed Forces, we have the opportunity to live and work. Also during last months all regions of Ukraine experienced horrible missile attacks of Russian invaders.
Night work and breast cancer risk in a cohort of female healthcare employees in Stockholm, Sweden
Authors: Gustavsson Per , Bigert Carolina , Andersson Tomas , Kader Manzur , Härmä Mikko , Selander Jenny , Bodin Theo , Albin Maria
Published: May 2023

Objectives

Night work has been classified as probably carcinogenic to humans by the International Agency for Research on Cancer, but epidemiological evidence was considered limited due to variability in findings and potential bias. This study aimed to investigate the risk of breast cancer in a cohort with detailed and registry-based data on night work.

Methods

The cohort comprised 25 585 women (nurses and nursing assistants) employed 1 year or more between 2008 and 2016 in the healthcare sector in Stockholm. Information on work schedules was obtained from employment records. Breast cancer cases were identified from the national cancer register. HRs were estimated by a discrete time proportional hazards model, adjusting for age, country of birth, profession and childbirth.

Results

There were 299 cases of breast cancer, 147 in premenopausal and 152 in postmenopausal women. The adjusted HR of postmenopausal breast cancer in association with ever versus never working nights was 1.31 (95% CI 0.91 to 1.85). Eight or more years of night work was associated with an increased risk of postmenopausal breast cancer, HR=4.33 (95% CI 1.45 to 10.57), based on five cases only, though.

Conclusions

This study is limited by a short period of follow-up and a lack of information on night work before 2008. Most exposure metrics showed no association with breast cancer risk, but there was an elevated risk of postmenopausal breast cancer in women after 8 or more years of night work.
Detailed phenotype ofRNF213p.R4810K variant identified by the Chinese patients with acute ischaemic stroke or transient ischaemic attack
Authors: Zhou Hongyu , Jing Jing , Pu Yuehua , Li Wei , Meng Xia , Wang Anxin , Zuo Yingting , Xu Zhe , Xu Qin , Suo Yue , Li Hao , Wang Yongjun
Published: May 2023

Background and purpose

The ring finger protein 213 gene (RNF213) p.R4810K variant increased the risk of acute ischaemic stroke (AIS) attributable to intracranial arterial stenosis (ICAS) in the Japanese and Korean populations. In this study, we aimed to examine the prevalence of theRNF213p.R4810K variant in Chinese patients with AIS or transient ischaemic attack and identify the phenotype of the carriers.

Methods

We analysed data from the Third China National Stroke Registry. All included participants were divided into two groups by carrier status of the p.R4810K variant. The aetiological classification was conducted according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. The presence of ICAS and extracranial arterial stenosis (ECAS) was defined as 50%–99% stenosis or occlusion of any intracranial and extracranial artery. Logistic regression models and Cox regression models were used to evaluate the association of the p.R4810K variant with TOAST classification, stenosis phenotypes and clinical outcomes.

Results

A total of 10 381 patients were enrolled, among which 56 (0.5%) had the heterozygote GA genotype for p.R4810K. The variant carriers were younger (p=0.01), and more likely to suffer from peripheral vascular disease (p=0.04). The p.R4810K variant was associated with large-artery atherosclerosis (LAA) (adjusted OR=1.94, 95% CI 1.13 to 3.33), anterior circulation stenosis (adjusted OR=2.12, 95% CI 1.23 to 3.65) and ECAS (adjusted OR=2.29, 95% CI 1.16 to 4.51). Nevertheless, the p.R4810K variant was not associated with recurrence, poor functional outcome and mortality at 3 months and 1 year.

Conclusions

TheRNF213p.R4810K variant was associated with LAA, anterior circulation stenosis and ECAS in Chinese patients. Given the low carrying rate and only 1-year follow-up information, caution should be taken to interpret our findings in no statistically significant association between the p.R4810K variant and stroke prognosis in Chinese patients.
Prestroke physical activity is associated with admission haematoma volume and the clinical outcome of intracerebral haemorrhage
Authors: Viktorisson Adam , Buvarp Dongni , Danielsson Anna , Skoglund Thomas , S Sunnerhagen Katharina
Published: May 2023

Background

Prestroke physical activity (PA) has been linked to improved outcomes after intracerebral haemorrhage (ICH), but its association with ICH volume is unknown. We aimed to investigate associations of prestroke PA with location-specific haematoma volume and the clinical outcome of ICH.

Methods

All patients with primary ICH, admitted to three hospitals between 2014 and 2019, were included. Patients performing light PA ≥4 hour/week the year before stroke were considered physically active. Haematoma volumes were assessed from admission brain imaging. Adjusted associations were estimated using multivariate linear and logistic regression models. Haematoma volume was explored as mediator to the relationship between prestroke PA and mild stroke severity (0–4 points on the National Institutes of Health Stroke Scale), a good 1-week functional status (0–3 points on the modified Rankin Scale) and 90-day survival. Average direct effects (ADE) and average causal mediation effects (ACME) were computed.

Results

Of 686 primary ICH cases, 349 were deep, 240 lobar and 97 infratentorial. Prestroke PA predicted smaller haematoma volumes in deep ICH (β=−0.36, SE=0.09, p<0.001) and lobar ICH (β=−0.23, SE=0.09, p=0.016). Prestroke PA was also associated with mild stroke severity (OR 2.53, 95% CI 1.59 to 4.01), a good 1-week functional status (OR 2.12, 95% CI 1.37 to 3.30) and 90-day survival (OR 3.48, 95% CI 2.06 to 5.91). Haematoma volume partly mediated the relationships between PA and stroke severity (ADE 0.08, p=0.004; ACME 0.10, p<0.001), 1-week functional status (ADE 0.07, p=0.03; ACME 0.10, p<0.001) and 90-day survival (ADE 0.14, p<0.001; ACME 0.05, p<0.001).

Conclusions

Light PA ≥4 hour/week prior to ICH was associated with smaller haematoma volumes in deep and lobar locations. Physically active patients with ICH had a higher likelihood of mild stroke, a good 1-week functional status and 90-day survival, in part mediated by smaller haematoma volumes on admission.
A comprehensive content analysis of 104 Chinese electronic cigarette manufacturing enterprise official websites
Authors: Deng Hui , Fang Ling , Zhang Lingyun , Yan Xiaotao , Wang Fan , Hao Xinyu , Zheng Pinpin
Published: May 2023

Objective

The goal was to analyse website content of Chinese electronic (e) cigarette manufacturing enterprises and understand the marketing strategies to provide evidence for decision-makers to regulate manufacturers.

Methods

Through QCC.com, one of the largest enterprise information query platforms in China, we identified 104 official manufacturer websites in 2021. A codebook including 6 sections with 31 items was developed and all webpages were coded separately by two trained researchers.

Results

Over half of the websites (56.7%) did not have age verification for entry. Thirty-two (30.8%) websites had no restriction for minors to use or purchase e-cigarettes, and 79 (76.0%) had no health warning. Overall, 99 websites (95.2%) displayed their products, and 72 (69.2%) displayed e-flavours. The most frequently used descriptions of products included good taste (68.3%), positive mood (62.5%), leakage resistance (56.7%), enjoyment (47.1%), reduced harm (45.2%), alternatives to cigarettes (43.3%) and long battery life (42.3%). Additionally, 75 websites (72.1%) provided contact information on different channels, including WeChat (59.6%), Weibo (41.3%), Facebook (13.5%), Instagram (12.5%) and brand apps (2.9%). Manufacturers provided investment and franchise information (59.6%) and offline store information (17.3%). In addition, 41.3% websites included content regarding corporate social responsibility.

Conclusions

Chinese e-cigarette manufacturers’ official websites have become a platform for presenting product and brand information, establishing online and offline marketing loops, and displaying corporate social responsibility with weak age restrictions on access and a lack of health warnings. The Chinese government should implement strict regulatory measures on e-cigarette enterprises.
Older age is associated with greater misperception of the relative health risk of e-cigarettes and cigarettes among US adults who smoke
Authors: Rubenstein Dana , Denlinger-Apte Rachel L , Cornacchione Ross Jennifer , Carroll Dana Mowls , McClernon F Joseph
Published: May 2023

Introduction

The prevalence of cigarette smoking among adults aged ≥55 has remained stagnant over the past decade. National data modelling suggests no reduction in cigarette smoking prevalence attributable to e-cigarette use in the USA among people aged ≥45. Misperceptions about the absolute risks (ie, cigarettes are not harmful) and relative risks (ie, e-cigarettes are more harmful than cigarettes) of tobacco products may contribute to sustained smoking prevalence and hesitancy to switch from cigarettes to e-cigarettes among older adults.

Methods

Participants reported cigarette use (n=8072) at Wave 5 (2018–2019) of the Population Assessment of Tobacco and Health Study. Weighted multivariable logistic regressions included six age categories (independent variable) and cigarette and e-cigarette risk perceptions (outcomes). Additional models assessed the associations between dichotomous age (≥55 vs 18–54), risk perceptions and an interaction term (independent variables) with past 12-month quit attempts and past-month e-cigarette use (outcomes).

Results

Adults aged ≥65 were less likely than adults aged 18–24 to rate cigarettes as very/extremely harmful (p<0.05). Odds of rating e-cigarettes as more harmful than cigarettes among adults aged 55–64 and ≥65 were 1.71 (p<0.001) and 1.43 (p=0.024) greater than for adults aged 18–24. This misperception was negatively associated with past-month e-cigarette use and was stronger among adults aged ≥55 (p<0.001) than adults aged <55 (p<0.001).

Discussion

Adults aged ≥55 are more likely to have misperceptions about the absolute and relative risks of tobacco products, which may contribute to continued smoking. Health communications targeting this age group could modify beliefs about the perceived harms of tobacco products.
Massive particle pair production and oscillation in Friedman Universe: reheating energy and entropy, and cold dark matter
Authors: Xue She-Sheng
Published: May 2023

Suppose that the early Universe starts with a cosmological $$\Lambda $$
Λ
-term (dark energy) originating from quantum spacetime at the Planck scale. Dark energy drives inflation and reheating by reducing its value for massive particle–antiparticle pairs production and oscillation, resulting in a holographic and massive pair plasma state. The back-and-forth reaction of dark energy and massive pairs slows inflation to its end and starts reheating by rapidly producing stable and unstable pairs. We introduce the Boltzmann-type rate equation describing the back-and-forth reaction. It forms a close set with Friedman equations and reheating equations for unstable pairs decay to relativistic particles. The numerical solutions show preheating, massive pairs dominated and genuine reheating episodes. We obtain the reheating temperature and entropy in terms of the tensor-to-scalar ratio $$0< r < 0.047$$

0
<
r
<
0.047

consistently with observations. Stable massive pairs represent cold dark matter particles and weakly interact with dark energy. The resultant cold dark matter abundance $$\Omega _c\sim 10^{-1}$$

Ω
c

∼

10

-
1

is about a constant in time.
A Novel Clustering Algorithm for Monitoring Paddy Growth Through Satellite Image Processing.
Authors: R Sathiya Priya , U Rahamathunnisa
Published: May 2023

In agriculture, paddy crop monitoring placed a crucial role because it supports food security control. Water shortage, high cost of fertilizers, and soil deterioration were identified as some of the difficulties encountered when monitoring rice crops through satellite images acquired by remote sensing. This study developed a deep learning method-assisted clustering algorithm (DLCA) which helps to improve the paddy growth identification process and enables the transparency of agricultural activity. Convolution neural network (CNN) has been utilized to identify crop growth which helps to understand drip irrigation and water scarcity for a particular crop. The experimental research shows that the proposed model is improved in identifying the paddy growth, soil availability, high cost of fertilizers, and soil degradation in monitoring paddy crop production through the satellite image process. Overall, the findings of the experiments have been carried out, and the proposed DLCA to achieve a lower error rate of 0.03 and high accuracy of 98.52%, MCC attains 98.43%, and F1-score 99.02% compared to other popular methods.
Component-based Distributed Software Reconfiguration:A Verification-oriented Survey
Authors: Coullon Héléne , Henrio Ludovic , Loulergue Frédéric , Robillard Simon
Published: May 2023

Distributed software built from components has become a mainstay of service-oriented applications, which frequently undergo reconfigurations to adapt to changes in their operating environment or their functional requirements. Given the complexity of distributed software and the adverse effects of incorrect reconfigurations, a suitable methodology is needed to ensure the correctness of reconfigurations in component-based systems. This survey gives the reader a global perspective over existing formal techniques that pursue this goal. It distinguishes different ways in which formal methods can improve the reliability of reconfigurations, and lists techniques that contribute to solving each of these particular scientific challenges.
Memristive-based Mixed-signal CGRA for Accelerating Deep Neural Network Inference
Authors: Kazerooni-Zand Reza , Kamal Mehdi , Afzali-Kusha Ali , Pedram Massoud
Published: May 2023

In this paper, a mixed-signal
coarse-grained reconfigurable architecture (CGRA)
for accelerating inference in
deep neural networks (DNNs)
is presented. It is based on performing dot-product computations using analog computing to achieve a considerable speed improvement. Other computations are performed digitally. In the proposed structure (called MX-CGRA), analog tiles consisting of memristor crossbars are employed. To reduce the overhead of converting the data between analog and digital domains, we utilize a proper interface between the analog and digital tiles. In addition, the structure benefits from an efficient memory hierarchy where the data is moved as close as possible to the computing fabric. Moreover, to fully utilize the tiles, we define a set of micro instructions to configure the analog and digital domains. Corresponding context words used in the CGRA are determined by these instructions (generated by a companion compiler tool). The efficacy of the MX-CGRA is assessed by modeling the execution of state-of-the-art DNN architectures on this structure. The architectures are used to classify images of the ImageNet dataset. Simulation results show that, compared to the previous mixed-signal DNN accelerators, on average, a higher throughput of 2.35 × is achieved.
In Situ Prussian Blue-Electrocatalyst Formation on Intrinsic Iron-Containing Pristine-MWCNT as a Template and Its EQCM and SECM Interrogations and Batch Injection Analysis of Hydrogen Peroxide
Authors: Kumar Annamalai Senthil , Saikrithika Sairaman , Yesudas Yashly K.
Published: May 2023

Herein, we report in-situ electrochemical derivatization of the intrinsic iron species in a pristine-multiwalled carbon nanotube (MWCNT) as Prussian blue (PB) modified MWCNT hybrid (MWCNT@PB) using a dilute solution of ferricyanide as a derivatization agent in pH 2 HCl-KCl solution. The PB hybrid system showed a defined redox peak at an apparent standard electrode potential, Eo’ = 0.18 V vs Ag/AgCl with an excess surface value, 1.71 × 10−10 mol cm−2. A discreet EQCM study on the electrochemical preparation of MWCNT@PB using MWCNT and ferricyanide precursors reveal the specific stripping of iron species and uptake of iron species, potassium and ferricyanide ions upon the electrochemical preparation condition. In-situ imaging of MWCNT@PB was carried out using SECM with ferricyanide as a redox mediator under a feedback-current mode. It has been identified that a mixed-potential based electrochemical reaction involving oxidative stripping of iron to iron ion species (step-1) coupled with reduction of ferricyanide to ferrocyanide (step-2) followed by a chemical interaction between the iron ion and ferricyanide (step-3) have occurred for the overall formation of MWCNT@PB hybrid. Electrocatalytic and electroanalytical performance of the MWCNT@PB hybrid towards H2O2 reduction and sensing were demonstrated by performing cyclic voltammetric, amperometric i-t and batch injection analysis.
Preparation of CuO/rGO Nanocomposite with Rice Granular Structure and Its Application to Detect Glucose
Authors: Ruifeng Li , Yue Chen , Weitong Yang , Min Deng , Xiaoying Lu , Qi Jiang
Published: May 2023

In order to enhance the electrochemical detection performance for glucose, graphene oxide (GO) was introduced during the preparation process of micron-sized rice granular CuO. A nano-sized rice CuO/rGO composite chemically modified electrode with good conductivity was prepared and used for the enzyme-free detection on glucose. The morphology and structure of the samples were characterized by scanning electron microscope, X-ray diffraction, Raman spectroscopy and N2 adsorption desorption tester. The electrochemical properties of the prepared modified electrode were tested by cyclic voltammetry, amperometric experiments and AC impedance testing. The results show that the prepared nanocomposite still retains the rice grain structure of the original CuO, but the particle size is reduced in to nanometer scale. When the mass ratio of CuO and rGO is 3.5:1, the modified electrode has the strongest current response to glucose: in the range of 0.01 to 2.53 mmol·l−1, there is a good linear relationship and the linear equation is I

pa
(Ma) = (2.81 ± 0.08) × 10−2 + (9.63 ± 0.06) × 10−2
c (mmol·l−1), R = 0.999. The detection limit is 0.047 mol·l−1 (S/N = 3) and the sensitivity is 1746.16 μA·mmol−1·L·cm−2. At the same time, the prepared modified electrode has good selectivity, reliability, repeatability and stability for glucose.
A Rare Case of Ruptured Tailgut Cyst Leading to Carcinomatosis
Authors: Atiya Samir , Horn Adam , Wedel Whitney , Lintel Nicholas
Published: May 2023

Tailgut cysts are congenital cysts arising in the retrorectal space. They are thought to be benign with variable malignancy risks. We report a case with previous surgical intervention decades prior that had undergone a tailgut cyst excision with surgical complications leading to carcinomatosis. An elderly female (70s) presented with tailbone/pelvic pain. She underwent cyst excision that was complicated by an intraoperative rupture. The cyst was pathologically proven to be a tailgut cyst with adenocarcinoma. She presented 13 months postoperatively to the emergency department with worsening abdominal pain. Imaging was concerning for diffuse omental nodules and narrowing of the proximal sigmoid colon. She was not deemed to be a surgical candidate and was transitioned to hospice care, where she passed away shortly afterward. This case report highlights the utility of complete excision of tailgut cysts and possible complications.
Research on Model Construction of Electric Energy Metering System Based on Intelligent Sensor Data
Authors: Li Hang , Bai Luwei , Yu Jia , Mao Yongmei , Hui Zhenzhen
Published: May 2023

The informatization construction of the power grid is becoming increasingly popular, business application systems are constantly emerging, and power-related data is rapidly expanding. These discrete power data are scattered in various application systems, and it is not easy to directly provide advanced enterprise applications. The establishment of intelligent power statistical model is an urgent need for constructing power grid informatization. This paper proposes a model of an electric energy metering system based on intelligent sensor data and introduces the existing digital metering system. This model is the integration and promotion of business integration based on the digital metering system. It is the first time to apply new metering equipment, such as measurement and control devices with integrated metering functions, and new metering technologies, such as IEC 61850 electricity meter reading applications. It is hoped that this paper can lay a foundation for further research.
PLAP: CSI-Based Passive Localization with Amplitude and Phase Information Using CNN and BGRU
Authors: Wang Qian , Yao Qingguo , Li Yuli , Zhang Yansong , Xu Cuicui
Published: May 2023

With the increasing popularization and development of WiFi devices, nowadays WiFi-based indoor localization has become a hot topic. Traditional Wi-Fi-based localization technologies which utilize received signal strength indication suffer from indoor multi-path effects and result in localization performance degradation. Therefore, choosing the appropriate characteristic of the WiFi signal is crucial for indoor localization. To improve the localization accuracy, we propose PLAP, a passive localization method using amplitude and phase of channel state information (CSI). Specifically, Hampel filter is used to process the amplitude signals and linear transformation is employed for calibrating phases. To extract representative features from calibrated amplitude and phase signals, we developed a deep learning framework which combines a convolutional neural network (CNN) and a bi-directional Gated recurrent unit (BGRU) to estimate the location of an objective. The experimental results show that the proposed PLAP outperforms other baselines with real-world evaluation.
One-Pot Synthesis of Biodiesel from Acid Oil Using a Switchable Solvent, 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU), as a Bifunctional Catalyst
Authors: Nguyen Hoang Chinh , Pham Thanh Truc , Nguyen Nguyen Phuong , Aregawi Beyene Hagos , Fu Chun-Chong , Barrow Colin J. , Su Chia-Hung , Wu Shao-Jung , Juan Horng-Yi
Published: May 2023

Biodiesel is a promising alternative to petrodiesel, but its production from acid oils retains several technical challenges. Therefore, this study developed a new approach involving 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)-catalyzed one-pot reaction (simultaneous esterification-transesterification) to produce biodiesel with enhanced reaction efficiency. The reaction was performed under water removal conditions and optimized using response surface methodology to maximize the biodiesel yield. The optimal conditions for the one-pot reaction had a reaction time of 2.73 h, temperature of 143°C, methanol:oil molar ratio of 24.3 : 1, and DBU loading of 30.1%. Under the optimal conditions, maximum total biodiesel of 97.1% was obtained. DBU could be repeatedly used for at least 5 cycles to yield over 91% biodiesel. This study suggests that DBU efficiently catalyzed esterification and transesterification simultaneously and the DBU-catalyzed one-pot reaction is an efficient method for biodiesel production from high-free-fatty acid oils.
Transfer and Deep Learning‐Based Gurmukhi Handwritten Word Classification Model
Authors: Singh Tajinder Pal , Gupta Sheifali , Garg Meenu , Verma Amit , Hung V. V. , Thien H. H. , Islam Md Khairul
Published: May 2023

The world is having a vast collection of text with abandon of knowledge. However, it is a difficult and time‐taking process to manually read and recognize the text written in numerous regional scripts. The task becomes more critical with Gurmukhi script due to complex structure of characters motivated from the challenges in designing an error‐free and accurate classification model of Gurmukhi characters. In this paper, the author has customized the convolutional neural network model to classify handwritten Gurmukhi words. Furthermore, dataset has been prepared with 24000 handwritten Gurmukhi word images with 12 classes representing the month’s names. The dataset has been collected from 500 users of heterogeneous profession and age group. The dataset has been simulated using the proposed CNN model as well as various pretrained models named as ResNet 50, VGG19, and VGG16 at 100 epochs and 40 batch sizes. The proposed CNN model has obtained the best accuracy value of 0.9973, whereas the ResNet50 model has obtained the accuracy of 0.4015, VGG19 has obtained the accuracy of 0.7758, and the VGG16 model has obtained value accuracy of 0.8056. With the current accuracy rate, noncomplex architectural pattern, and prowess gained through learning using different writing styles, the proposed CNN model will be of great benefit to the researchers working in this area to use it in other ImageNet‐based classification problems.
INKA2-AS1 Is a Potential Promising Prognostic-Related Biomarker and Correlated with Immune Infiltrates in Hepatocellular Carcinoma
Authors: Li Wenke , Hong Guoqing , Lai Xing
Published: May 2023

Hepatocellular carcinoma (HCC) is a malignancy with one of the worst prognoses. Long noncoding RNAs (lncRNAs) may be important in cancer development and may serve as new biomarkers for the diagnosis and treatment of various tumors, according to mounting research. The purpose of this study was to investigate the expression of INKA2-AS1 and clinical importance in HCC patients. The TCGA database was used to obtain the human tumor samples, while the TCGA and GTEx databases were used to gather the human normal samples. We screened differentially expressed genes (DEGs) between HCC and nontumor tissues. Investigations were made into the statistical significance and clinical significance of INKA2-AS1 expression. A single-sample gene set enrichment analysis (ssGSEA) was used to examine potential relationships between immune cell infiltration and INKA2-AS1 expression. In this investigation, we found that HCC specimens had considerably greater levels of INKA2-AS1 expression than nontumor specimens. When utilizing the TCGA datasets and the GTEx database, high INKA2-AS1 expression showed an AUC value for HCC of 0.817 (95% confidence interval: 0.779 to 0.855). Pan-cancer assays revealed that numerous tumor types had dysregulated levels of INKA2-AS1. Gender, histologic grade, and pathologic stage were all substantially correlated with high INKA2-AS1 expression. A survival study indicated that HCC patients with high INKA2-AS1 expression have shorter OS, DSS, and PFI than those with low INKA2-AS1 expression. Multivariate analysis indicated that INKA2-AS1 expression was an independent prognostic factor for OS of patients with HCC. According to immune analysis, the expression of INKA2-AS1 was favorably correlated with T helper cells, Th2 cells, macrophages, TFH, and NK CD56bright cells and negatively correlated with Th17 cells, pDC, cytotoxic cells, DC, Treg, Tgd, and Tcm. The results of this study collectively suggest that INKA2-AS1 has the potential to be a novel biomarker for predicting the prognosis of HCC patients as well as a significant immune response regulator in HCC.
Combat Response Training Tester Based on Intelligent Force-Measuring Sensor and Digital Circuit
Authors: Liu Chen
Published: May 2023

In combat sports, the team members take attack and defense as the core of sports, and the technical movements are not periodic and the application process is irregular. During the competition, observe the opponent’s neutral position, judge timely, and react quickly. At the same time, athletes are required not only to master skilled technical movements but also to have rapid and accurate adaptability. In order to improve athletes’ rapid response ability, according to the rapid response training scheme, a combat response training tester based on a force-measuring intelligent sensor and digital circuit is designed to improve the athletes’ response ability. Firstly, a comprehensive test system of combat trainer is designed based on the intelligent force-measuring sensor and MSP430, which can measure the response time, speed, and strength of boxing. Secondly, a wavelet filtering algorithm is used to filter the sensor measurement data. Finally, the striking force and striking time of each action are recorded by sensors and data acquisition devices to reflect the striking effect and reflect the “accurate” objectives of the project characteristics. Based on the noninterference and anti-interference of e-touch piezoelectric film, it can be made into universal force-measuring sensors of different specifications for fight competitions according to needs. After being connected into a module network in parallel, it can be connected with the microcontroller to determine the hit area. In addition, the team reaction training test device has laid a foundation for the scientific evaluation of improving the team members’ reaction ability and attack defense conversion ability. The launch of the comprehensive ability tester for combat athletes introduces the previous fuzzy evaluation of athletes’ comprehensive ability into a new way of scientific quantitative measurement and evaluation, which will provide a scientific basis for the selection of combat vibration items, the regulation of training process, the inspection of training effect, and the formulation of enrollment and examination standards for sports colleges and universities. The results show that the instrument can obtain the parameters of hitting strength, strength endurance, hitting speed, speed endurance, hitting impulse, and hitting power of sports biomechanics on the group of fighting events, which provides a reliable basis for coaches to implement teaching and training for athletes.
Incorporating the Theory of Planned Behaviour into Distracted Driving: Influencing Factors and Intervention Effects
Authors: Zhang L. , Peng J. S. , Song Z. , Fan Z. B. , Yang X. H. , Kong Q. W. , Zhou L.
Published: May 2023

This study focuses on the psychological characteristics and empirically tests of the factors influencing distracted driving behaviours. This information is used as a reference for an intervention on dangerous driving behaviours. First, a distracted driving scale is constructed based on the theory of planned behaviour (TPB). The questionnaires are distributed in Chongqing, China, and 321 completed questionnaires are obtained. Data are analyzed using mean-variance analysis, one-way ANOVA, T-test, and multivariate test by SPSS 26.0 to determine the significance of distracted behaviours and demographic variables. We use a structural equation model to determine the path coefficients of each latent variable. Finally, we select the drivers with high tendency of distraction from the results of the questionnaires, conduct a four-stage rational emotional behaviour therapy (REBT) experiment, and use a repeated measures ANOVA analysis to test the validity and persistence of the intervention method. Results show that subjective norm is the most influential psychological factor. There are significant differences between the experimental group (2.38, SD = 0.41) and the control group (2.89, SD = 0.40) in the scores of distractions. This indicates that the distracted behaviour intervention achieves adequate validity and consistency. Educational research on distracted driving behaviour can help identify and correct drivers with high distraction tendency.
Academic Emotion Classification Using FER: A Systematic Review
Authors: Lek Jeniffer Xin-Ying , Teo Jason
Published: May 2023

Facial emotion expressions are among the most potent, natural, and powerful means of human communication. Due to the COVID-19 pandemic, educational institutions worldwide are forced to switch rapidly to remote and online learning. Students are currently in an emergency state and must adapt to various and readily accessible learning methods, such as mobile learning applications or an e-learning system. A systematic literature review (SLR) is conducted to extract and synthesize information such as the emotion classifier used in the facial expression recognition (FER) system, the dataset used, the preprocessing technique applied, the feature extraction approach used, and the strength and limitation of the previous studies. Based on the search criteria, 701 publications were initially retrieved from five different digital databases, of which 48 studies have been chosen as primary studies for further analysis. Based on the findings of this study, the deep learning approach is the most frequently adopted approach in classifying student emotions during online learning. FER-2013 is the most commonly used FER dataset in FER studies, while DAiSEE is the most used academic emotion dataset. Moreover, support vector machine (SVM) is the conventional learning emotion classifier that is widely used in the FER systems, while convolutional neural network (CNN) is the most frequently used deep learning classifier. Next, it was found that the number of real-time FER systems is less than that of non-real-time FER systems. Finally, the top-1 accuracy of 94.6% was achieved by the long-term recurrent convolutional network on the academic emotion dataset, and the limitation is that it has low illumination and a lack of frontal pose.
A Computational Study on Selected Alkaloids as SARS-CoV-2 Inhibitors: PASS Prediction, Molecular Docking, ADMET Analysis, DFT, and Molecular Dynamics Simulations
Authors: Mortuza Md. Golam , Roni Md Abul Hasan , Kumer Ajoy , Biswas Suvro , Saleh Md. Abu , Islam Shirmin , Sadaf Samia , Akther Fahmida
Published: May 2023

Despite treatments and vaccinations, it remains difficult to develop naturally occurring COVID-19 inhibitors. Here, our main objective is to find potential lead compounds from the retrieved alkaloids with antiviral and other biological properties that selectively target the main SARS-CoV-2 protease (Mpro), which is required for viral replication. In this work, 252 alkaloids were aligned using Lipinski’s rule of five and their antiviral activity was then assessed. The prediction of activity spectrum of substances (PASS) data was used to confirm the antiviral activities of 112 alkaloids. Finally, 50 alkaloids were docked with Mpro. Furthermore, assessments of molecular electrostatic potential surface (MEPS), density functional theory (DFT), and absorption, distribution, metabolism, excretion, and toxicity (ADMET) were performed, and a few of them appeared to have potential as candidates for oral administration. Molecular dynamics simulations (MDS) with a time step of up to 100 ns were used to confirm that the three docked complexes were more stable. It was found that the most prevalent and active binding sites that limit Mpro’sactivity are PHE294, ARG298, and GLN110. All retrieved data were compared to conventional antivirals, fumarostelline, strychnidin-10-one (L-1), 2,3-dimethoxy-brucin (L-7), and alkaloid ND-305B (L-16) and were proposed as enhanced SARS-CoV-2 inhibitors. Finally, with additional clinical or necessary study, it may be able to use these indicated natural alkaloids or their analogs as potential therapeutic candidates.
Coronary Stent Abscess in the Setting of Arteriovenous Graft Infection following COVID-19: An Autopsy Case Report
Authors: Butler Jean Thompson , Chellappan Rajeshwari , Litovsky Silvio , Leal Sixto M. , Benson Paul V.
Published: May 2023

While rare, coronary stent infections present with significant mortality—with most infections and further complications occurring within months of percutaneous coronary intervention (PCI). Here, we discuss a post-COVID-19 patient who presented approximately one year after PCI for declotting of an arteriovenous graft (AVG). Upon admission, the patient was found to be bacteremic with multilobar pneumonia and an infection of the AVG. Empiric antibiotics were started, and blood cultures were subsequently positive for MRSA. Removal of the AVG was unsuccessful, and two days after admission, the patient passed. Autopsy revealed a perivascular abscess in the RCA near the origin of the stent with a ground section of the RCA with stent revealing abundant calcific atherosclerosis and marked necrosis of the artery wall. The cause of death was determined to be sepsis complicating coronary artery disease and chronic renal failure.
Table S2 from Clinical Importance of the lncRNA NEAT1 in Cancer Patients Treated with Immune Checkpoint Inhibitors
Authors: Toker Joseph , Iorgulescu J. Bryan , Ling Alexander L. , Villa Genaro R. , Gadet Josephina A.M.A. , Parida Laxmi , Getz Gad , Wu Catherine J. , Reardon David A. , Chiocca E. Antonio , Mineo Marco
Published: May 2023

Melanoma patient characteristics (GSE78220)
Data from Proinflammatory Macrophage Activation by the Polysialic Acid-Siglec-16 Axis Is Linked to Increased Survival of Patients with Glioblastoma
Authors: Thiesler Hauke , Gretenkort Lina , Hoffmeister Leonie , Albers Iris , Ohlmeier Luisa , Röckle Iris , Verhagen Andrea , Banan Rouzbeh , Köpcke Nora , Krönke Nicole , Feuerhake Friedrich , Behling Felix , Barrantes-Freer Alonso , Mielke Dorothee , Rohde Veit , Hong Bujung , Varki Ajit , Schwabe Kerstin , Krauss Joachim K. , Stadelmann Christine , Hartmann Christian , Hildebrandt Herbert
Published: May 2023

AbstractPurpose:
Interactions with tumor-associated microglia and macrophages (TAM) are critical for glioblastoma progression. Polysialic acid (polySia) is a tumor-associated glycan, but its frequency of occurrence and its prognostic value in glioblastoma are disputed. Through interactions with the opposing immune receptors Siglec-11 and Siglec-16, polySia is implicated in the regulation of microglia and macrophage activity. However, due to a nonfunctional SIGLEC16P allele, SIGLEC16 penetrance is less than 40%. Here, we explored possible consequences of SIGLEC16 status and tumor cell–associated polySia on glioblastoma outcome.
Experimental Design:
Formalin-fixed paraffin-embedded specimens of two independent cohorts with 70 and 100 patients with newly diagnosed glioblastoma were retrospectively analyzed for SIGLEC16 and polySia status in relation to overall survival. Inflammatory TAM activation was assessed in tumors, in heterotypic tumor spheroids consisting of polySia-positive glioblastoma cells and Siglec-16–positive or Siglec-16–negative macrophages, and by exposing Siglec-16–positive or Siglec-16–negative macrophages to glioblastoma cell–derived membrane fractions.
Results:
Overall survival of SIGLEC16 carriers with polySia-positive tumors was increased. Consistent with proinflammatory Siglec-16 signaling, levels of TAM positive for the M2 marker CD163 were reduced, whereas the M1 marker CD74 and TNF expression were increased, and CD8+ T cells enhanced in SIGLEC16/polySia double-positive tumors. Correspondingly, TNF production was elevated in heterotypic spheroid cultures with Siglec-16–expressing macrophages. Furthermore, a higher, mainly M1-like cytokine release and activating immune signaling was observed in SIGLEC16-positive as compared with SIGLEC16-negative macrophages confronted with glioblastoma cell–derived membranes.
Conclusions:
Collectively, these results strongly suggest that proinflammatory TAM activation causes the better outcome in patients with glioblastoma with a functional polySia-Siglec-16 axis.
Data from MDM2 Inhibition Enhances Immune Checkpoint Inhibitor Efficacy by Increasing IL15 and MHC Class II Production
Authors: Langenbach Marlene , Giesler Sophie , Richtsfeld Stefan , Costa-Pereira Sara , Rindlisbacher Lukas , Wertheimer Tobias , Braun Lukas M. , Andrieux Geoffroy , Duquesne Sandra , Pfeifer Dietmar , Woessner Nadine M. , Menssen Hans D. , Taromi Sanaz , Duyster Justus , Börries Melanie , Brummer Tilman , Blazar Bruce R. , Minguet Susana , Turko Patrick , Levesque Mitchell P. , Becher Burkhard , Zeiser Robert
Published: May 2023

Abstract
The treatment of patients with metastatic melanoma with immune checkpoint inhibitors (ICI) leads to impressive response rates but primary and secondary resistance to ICI reduces progression-free survival. Novel strategies that interfere with resistance mechanisms are key to further improve patient outcome during ICI therapy. P53 is often inactivated by mouse-double-minute-2 (MDM2), which may decrease immunogenicity of melanoma cells. We analyzed primary patient-derived melanoma cell lines, performed bulk sequencing analysis of patient-derived melanoma samples, and used melanoma mouse models to investigate the role of MDM2-inhibition for enhanced ICI therapy. We found increased expression of IL15 and MHC-II in murine melanoma cells upon p53 induction by MDM2-inhibition. MDM2-inhibitor induced MHC-II and IL15-production, which was p53 dependent as Tp53 knockdown blocked the effect. Lack of IL15-receptor in hematopoietic cells or IL15 neutralization reduced the MDM2-inhibition/p53-induction–mediated antitumor immunity. P53 induction by MDM2-inhibition caused anti-melanoma immune memory as T cells isolated from MDM2-inhibitor–treated melanoma-bearing mice exhibited anti-melanoma activity in secondary melanoma-bearing mice. In patient-derived melanoma cells p53 induction by MDM2-inhibition increased IL15 and MHC-II. IL15 and CIITA expressions were associated with a more favorable prognosis in patients bearing WT but not TP53-mutated melanoma.
Implications:
MDM2-inhibition represents a novel strategy to enhance IL15 and MHC-II–production, which disrupts the immunosuppressive tumor microenvironment. On the basis of our findings, a clinical trial combining MDM2-inhibition with anti–PD-1 immunotherapy for metastatic melanoma is planned.
Data from Hedgehog Signaling Regulates Treg to Th17 Conversion Through Metabolic Rewiring in Breast Cancer
Authors: Hinshaw Dominique C. , Benavides Gloria A. , Metge Brandon J. , Swain Courtney A. , Kammerud Sarah C. , Alsheikh Heba A. , Elhamamsy Amr , Chen Dongquan , Darley-Usmar Victor , Rathmell Jeffrey C. , Welner Robert S. , Samant Rajeev S. , Shevde Lalita A.
Published: May 2023

Abstract
The tumor immune microenvironment dynamically evolves to support tumor growth and progression. Immunosuppressive regulatory T cells (Treg) promote tumor growth and metastatic seeding in patients with breast cancer. Deregulation of plasticity between Treg and Th17 cells creates an immune regulatory framework that enables tumor progression. Here, we discovered a functional role for Hedgehog (Hh) signaling in promoting Treg differentiation and immunosuppressive activity, and when Hh activity was inhibited, Tregs adopted a Th17-like phenotype complemented by an enhanced inflammatory profile. Mechanistically, Hh signaling promoted O-GlcNAc modifications of critical Treg and Th17 transcription factors, Foxp3 and STAT3, respectively, that orchestrated this transition. Blocking Hh reprogramed Tregs metabolically, dampened their immunosuppressive activity, and supported their transdifferentiation into inflammatory Th17 cells that enhanced the recruitment of cytotoxic CD8+ T cells into tumors. Our results demonstrate a previously unknown role for Hh signaling in the regulation of Treg differentiation and activity and the switch between Tregs and Th17 cells in the tumor microenvironment.
FIGURE 5 from Ultra High-plex Spatial Proteogenomic Investigation of Giant Cell Glioblastoma Multiforme Immune Infiltrates Reveals Distinct Protein and RNA Expression Profiles
Authors: Bonnett Shilah A. , Rosenbloom Alyssa B. , Ong Giang T. , Conner Mark , Rininger Aric B.E. , Newhouse Daniel , New Felicia , Phan Chi Q. , Ilcisin Saskia , Sato Hiromi , Lyssand John S. , Geiss Gary , Beechem Joseph M.
Published: May 2023

SPG exploration of GBM grade 4. A, A total of 42 cores across 23 distinct sample sources and multiple GBM types. ROIs were segmented into CD45+, GFAP+, or CD45−/GFAP−. B, Statistics from a single slide and single GeoMx SPG run. UMAP plots for protein (C) and RNA analytes (D).