bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual Semi-Supervised Learning for Classification of Alzheimer’s Disease and Mild Cognitive Impairment Based on Neuropsychological Data
Authors: Wang Yan , Gu Xuming , Hou Wenju , Zhao Meng , Sun Li , Guo Chunjie
Published: February 2023

Deep learning has shown impressive diagnostic abilities in Alzheimer’s disease (AD) research in recent years. However, although neuropsychological tests play a crucial role in screening AD and mild cognitive impairment (MCI), there is still a lack of deep learning algorithms only using such basic diagnostic methods. This paper proposes a novel semi-supervised method using neuropsychological test scores and scarce labeled data, which introduces difference regularization and consistency regularization with pseudo-labeling. A total of 188 AD, 402 MCI, and 229 normal controls (NC) were enrolled in the study from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. We first chose the 15 features most associated with the diagnostic outcome by feature selection among the seven neuropsychological tests. Next, we proposed a dual semi-supervised learning (DSSL) framework that uses two encoders to learn two different feature vectors. The diagnosed 60 and 120 subjects were randomly selected as training labels for the model. The experimental results show that DSSL achieves the best accuracy and stability in classifying AD, MCI, and NC (85.47% accuracy for 60 labels and 88.40% accuracy for 120 labels) compared to other semi-supervised methods. DSSL is an excellent semi-supervised method to provide clinical insight for physicians to diagnose AD and MCI.
Effects of Binaural Beat Stimulation in Adults with Stuttering
Authors: Chernetchenko Dmytro , Prasolov Pramax , Aganov Sam , Voropai Andrii , Polishchuk Yuliia , Lituiev Dmytro , Nayshtetik Eugene
Published: February 2023

In recent decades, several studies have demonstrated a link between stuttering and abnormal electroencephalographic (EEG) β-power in cortex. Effects of exposure to binaural stimuli were studied in adults with stuttering (AWS, n = 6) and fluent participants (n = 6) using EEG, ECG, and speech analysis. During standard reading tasks without stimulation, in controls but not in the AWS group, EEG β-power was significantly higher in the left hemisphere than in the right hemisphere. After stimulation, the power of the β-band in AWS participants in the left hemisphere increased 1.54-fold. The average β-band power within the left frontotemporal area and temporoparietal junction of the cortex after stimulation in AWS participants shows an increase by 1.65-fold and 1.72-fold, respectively. The rate of disfluency dropped significantly immediately after stimulation (median 74.70% of the baseline). Similarly, the speech rate significantly increased immediately after stimulation (median 133.15%). We show for the first time that auditory binaural beat stimulation can improve speech fluency in AWS, and its effect is proportional to boost in EEG β-band power in left frontotemporal and temporoparietal junction of cortex. Changes in β-power were detected immediately after exposure and persisted for 10 min. Additionally, these effects were accompanied by a reduction in stress levels.
Effects of Group Size on Behavior, Reproduction, and mRNA Expression in Brains of Brandt’s Voles
Authors: Lu Wei , Huang Shuli , Liu Jing , Batsuren Erdenetuya , Li Guoliang , Wan Xinru , Zhao Jidong , Wang Zuoxin , Han Wenxuan , Zhang Zhibin
Published: February 2023

For social animals, a moderate group size is greatly important to maintain their reproductive success. However, the underlying neurobiological mechanism of group size on behavior and reproduction has rarely been investigated. In this study, we examined the effects of group size (1, 2, 4 pairs of adult male and female voles raised per cage) on behavior and reproduction. Meanwhile, the mRNA expression of stress and reproduction response-related genes in male brains was detected. We found that Brandt’s voles (Lasiopodomys brandtii) in the large-sized group fight more severely than those in the small-sized group. Meanwhile, male voles were more anxious than females. The average number of embryos and litters per female in the medium-sized group was significantly higher than that of large-sized group. In male voles, stress- or reproduction-response mRNA expressions were more related to final group size or final density due to death caused by fighting. Our results indicated that a moderate group size was beneficial to the reproductive output of Brandt’s voles. Our study highlights the combined effects of stress- or reproduction-related gene expression or behavior in regulating the fitness of voles with different group sizes.
Dual Cannabinoid and Orexin Regulation of Anhedonic Behaviour Caused by Prolonged Restraint Stress
Authors: Kim Hye Ji J. , Zagzoog Ayat , Ceni Costanza , Ferrisi Rebecca , Janz Nicola , Laprairie Robert B.
Published: February 2023

The endocannabinoid and orexin systems share many biological functions, including wakefulness, stress response, reward processing, and mood. While these systems work against one another with respect to arousal, chronic stress-induced downregulation of both systems often leads to anhedonia or the inability to experience pleasure from natural rewards. In the current study, a 24 h restraint stress test (24 h RST) reduced sucrose preference in adult male and female C57BL/6 mice. Prior to the stressor, subsets of mice were intraperitoneally administered cannabinoid and orexin receptor agonists, antagonists, and combinations of these drugs. Restraint mice that received the cannabinoid receptor type 1 (CB1R) antagonist SR141716A, orexin receptor type 2 (OX2R) agonist YNT-185, and the combination of SR141716A and YNT-185, exhibited less anhedonia compared to vehicle/control mice. Thus, the 24 h RST likely decreased orexin signaling, which was then restored by YNT-185. Receptor colocalization analysis throughout mesocorticolimbic brain regions revealed increased CB1R-OX1R colocalization from SR141716A and YNT-185 treatments. Although a previous study from our group showed additive cataleptic effects between CP55,940 and the dual orexin receptor antagonist (TCS-1102), the opposite combination of pharmacological agents proved additive for sucrose preference. Taken together, these results reveal more of the complex interactions between the endocannabinoid and orexin systems.
Machine Learning Enabled P300 Classifier for Autism Spectrum Disorder Using Adaptive Signal Decomposition
Authors: Peketi Santhosh , Dhok Sanjay B.
Published: February 2023

Joint attention skills deficiency in Autism spectrum disorder (ASD) hinders individuals from communicating effectively. The P300 Electroencephalogram (EEG) signal-based brain–computer interface (BCI) helps these individuals in neurorehabilitation training to overcome this deficiency. The detection of the P300 signal is more challenging in ASD as it is noisy, has less amplitude, and has a higher latency than in other individuals. This paper presents a novel application of the variational mode decomposition (VMD) technique in a BCI system involving ASD subjects for P300 signal identification. The EEG signal is decomposed into five modes using VMD. Thirty linear and non-linear time and frequency domain features are extracted for each mode. Synthetic minority oversampling technique data augmentation is performed to overcome the class imbalance problem in the chosen dataset. Then, a comparative analysis of three popular machine learning classifiers is performed for this application. VMD’s fifth mode with a support vector machine (fine Gaussian kernel) classifier gave the best performance parameters, namely accuracy, F1-score, and the area under the curve, as 91.12%, 91.18%, and 96.6%, respectively. These results are better when compared to other state-of-the-art methods.
Oral Supplementation with Maca Improves Social Recognition Deficits in the Valproic Acid Animal Model of Autism Spectrum Disorder
Authors: Fu Pinyue , Luo Shuxin , Liu Zhongyu , Furuhara Kazumi , Tsuji Takahiro , Higashida Haruhiro , Yokoyama Shigeru , Zhong Jing , Tsuji Chiharu
Published: February 2023

Autism spectrum disorder (ASD) is a congenital, lifelong neurodevelopmental disorder whose main symptom is impaired social communication and interaction. However, no drug can treat social deficits in patients with ASD, and treatments to alleviate social behavioral deficits are sorely needed. Here, we examined the effect of oral supplementation of maca (Lepidium meyenii) on social deficits of in utero-exposed valproic acid (VPA) mice, widely used as an ASD model. Although maca is widely consumed as a fertility enhancer and aphrodisiac, it possesses multiple beneficial activities. Additionally, it benefits learning and memory in experimental animal models. Therefore, the effect of maca supplementation on the social behavioral deficit of VPA mice was assessed using a social interaction test, a three-stage open field test, and a five-trial social memory test. The oral supplementation of maca attenuated social interaction behavior deficit and social memory impairment. The number of c-Fos-positive cells and the percentage of c-Fos-positive oxytocin neurons increased in supraoptic and paraventricular neurons of maca-treated VPA mice. These results reveal for the first time that maca is beneficial to social memory and that it restores social recognition impairments by augmenting the oxytocinergic neuronal pathways, which play an essential role in diverse social behaviors.
Analysing Deception in Witness Memory through Linguistic Styles in Spontaneous Language
Authors: Solà-Sales Sara , Alzetta Chiara , Moret-Tatay Carmen , Dell’Orletta Felice
Published: February 2023

The act of lying and its detection have raised interest in many fields, from the legal system to our daily lives. Considering that testimonies are commonly based on linguistic parameters, natural language processing, a research field concerned with programming computers to process and analyse natural language texts or speech, is a topic of interest on this front. This study aimed to examine the linguistic styles of simulated deception and true testimonies collected with the aim of studying witness memory. Study participants were asked to act as a witness of a crime by retelling the story they had just read. Cognitive interviewing techniques were used to collect testimony under two conditions: truth and simulated deception. A sample of 48 participants volunteered to participate in the study. Analyses of the linguistic indicators and content were carried out. Specifically, we performed a comparison of testimonies of the same participant by condition to analyse the variation between (i) lexical and (ii) linguistic features and (iii) content and speech characteristics (disfluencies) depending on the narrative condition. Concerning lexical properties, adjectives were the most-varying grammatical category between truthful and deceptive testimonies. Furthermore, in the linguistic analysis, we observed that truthful testimonies were generally longer than deceptive ones in terms of the number of words and sentences and also characterised by more articulated sentence structures, and these differences were also statistically significant. Regarding the analysis of the content, cognitive criteria (details) and admitting lack of memory were more present in truthful statements. By providing an objective measure, these results are of interest in developing NLP tools for assessing the credibility of testimonies in forensics.
Wind-Induced Responses and Wind Loads on a Super High-Rise Building with Various Cross-Sections and High Side Ratio—A Case Study
Authors: Wang Qinhua , Zhang Buwen
Published: February 2023

With the development of construction technology and material, more and more super high-rise buildings will be constructed in the future. In a specific metropolitan area, super high-rise building with various cross-section and high side ratio have to been designed and constructed due to the size limitation of construction site. This kind of building is also very prone to wind excitations. In this research, wind tunnel tests for a practical case of this kind of building with surrounding buildings were carried out in atmospheric boundary wind tunnel. Equivalent static wind loads (ESWLs), wind-induced responses and wind load distribution on the building were analyzed. In particular, the base overturning moment along the axis with weak lateral stiffness were investigated for bearing capacity limit state design of the building. The results demonstrate that the maximum value of wind-induced base overturning moments and acceleration responses appears at 60° or 330° wind directions instead of the orthogonal wind direction, and the aerodynamic interference of surrounding buildings affects the wind pressure distribution on facades of the building. These results and conclusion may be helpful to wind-resistant design of super high-rise buildings with high side ratio.
Predictive Maintenance 4.0 for Chilled Water System at Commercial Buildings: A Methodological Framework
Authors: Almobarek Malek , Mendibil Kepa , Alrashdan Abdalla
Published: February 2023

Predictive maintenance is considered as one of the most important strategies for managing the utility systems of commercial buildings. This research focused on chilled water system (CWS) components and proposed a methodological framework to build a comprehensive predictive maintenance program in line with Industry 4.0/Quality 4.0 (PdM 4.0). This research followed a systematic literature review (SLR) study that addressed two research questions about the mechanism for handling CWS faults, as well as fault prediction methods. This research rectified the associated research gaps found in the SLR study, which were related to three points; namely fault handling, fault frequencies, and fault solutions. A framework was built based on the outcome of an industry survey study and contained three parts: setup, machine learning, and quality control. The first part explained the three arrangements required for preparing the framework. The second part proposed a decision tree (DT) model to predict CWS faults and listed the steps for building and training the model. In this part, two DT algorithms were proposed, C4.5 and CART. The last part, quality control, suggested managerial steps for controlling the maintenance program. The framework was implemented in a university, with encouraging outcomes, as the prediction accuracy of the presented prediction model was more than 98% for each CWS component. The DT model improved the fault prediction by more than 20% in all CWS components when compared to the existing control system at the university.
Estimating Maintenance Costs of Sewer System
Authors: Obradović Dino , Marenjak Saša , Šperac Marija
Published: February 2023

Maintenance costs of all types of buildings are most often ignored since they are incurred in the future. Potential investors are interested in capital costs—construction costs—while maintenance costs are considered as unimportant in the life cycle of a building. If there were a larger number of maintenance cost estimation models, it would be possible to estimate these costs and present them to potential investors more easily, thus making it easier and more effective to apply life cycle cost methods. A study on the characteristics and costs of the maintenance of sewer systems in the Republic of Croatia was conducted, wherein questionnaires were sent to companies operating public sewer systems. The data requested in the questionnaires were general data on enterprises, maintenance, data on sewer systems, quantities of sewer discharge, sewer pipes and data on maintenance costs of sewer systems. It was established that it is possible to use linear regression when creating a model for estimating the maintenance costs of a sewer system.
Assessing Factors Affecting Construction Equipment Productivity Using Structural Equation Modeling
Authors: Chandra Sathvik Sharath , Sepasgozar Samad M. E. , Kumar Varadhiyagounder Ranganathan Prasath , Singh Atul Kumar , Krishnaraj Loganathan , Awuzie Bankole Osita
Published: February 2023

The performance of the construction industry can be improved by understanding the factors that affect the productivity of its equipment. A hypothetical framework was used to analyze six vital construction equipment parameters to understand how they affect productivity in construction projects. Data collected through a survey of 110 respondents in the construction industry were analyzed using an exploratory factor analysis (EFA) and structural equation modeling (SEM). The final model obtained using SEM consisted of 31 attributes from six construction equipment productivity factors, namely management (MG), materials (MT), human (HM), technical (TN), environmental (EM), and other factors (OT). Construction equipment productivity was found to be significantly influenced by MT and OT in construction projects. This was mainly because of their corresponding subfactors, such as operating life and equipment age, and the occurrence of accidents during construction. Consequently, based on survey feedback from various construction professionals, present gaps in construction equipment productivity were analyzed, and recommendations were made to overcome the main limiting factors under MT and OT. This study identified and quantified the interrelationships between various construction equipment productivity constraints. Therefore, the results can help experts and specialists better comprehend how to overcome delays due to idle time and improve construction equipment productivity.
System Framework for Digital Monitoring of the Construction of Asphalt Concrete Pavement Based on IoT, BeiDou Navigation System, and 5G Technology
Authors: Zhang Jingxiao , Zhu Zhe , Liu Hongyong , Zuo Jian , Ke Yongjian , Philbin Simon P. , Zhou Zhendong , Feng Yunlong , Ni Qichang
Published: February 2023

In the construction of asphalt pavement, poor quality is often the main reason for damage to the pavement, which necessitates the use of monitoring systems during the construction stage. Therefore, this study focuses on building an asphalt concrete pavement construction monitoring system to monitor the construction phase. Through a literature review and semi-structured interviews with industry experts, this paper provides an in-depth understanding of the goals and obstacles of asphalt pavement monitoring and discusses directions for improvement. Subsequently, based on the analysis of the interview results, a system framework for asphalt concrete pavement construction monitoring was constructed, and the system was successfully developed and applied to a highway construction project. The results show that the monitoring system significantly improves the construction quality of asphalt concrete pavement, improves the intelligent level of pavement construction management, and promotes the digital development of highway construction.
GIS-Based Risk Assessment of Structure Attributes in Flood Zones of Odiongan, Romblon, Philippines
Authors: Gacu Jerome G. , Monjardin Cris Edward F. , de Jesus Kevin Lawrence M. , Senoro Delia B.
Published: February 2023

Flood triggered by heavy rains and typhoons leads to extensive damage to land and structures putting rural communities in crucial condition. Most of the studies on risk assessment focus on environmental factors, and building attributes have not been given attention. The five most expensive typhoon events in the Philippines were recorded in 2008–2013, causing USD 138 million in damage costs. This indicates the lack of tool/s that would aid in the creation of appropriate mitigation measure/s and/or program/s in the country to reduce damage caused by typhoons and flooding. Hence, this study highlights a structure vulnerability assessment approach employing the combination of analytical hierarchy process, physical structure attributes, and existing flood hazard maps by the local government unit. The available flood hazard maps were layered into base maps, and building attributes were digitized using a geographic information system. The result is an essential local scale risk map indicating the building risk index correlated to the structural information of each exposed structure. It was recorded that of 3094 structures in the community, 370 or 10.25% were found to be at moderate risk, 3094 (76.79%) were found to be high risk, and 503 (12.94%) were very high risk. The local government unit can utilize the resulting maps and information to determine flood risk priority areas to plan flood mitigation management strategies and educate people to improve the structural integrity of their houses. A risk map gives people an idea of what to improve in their houses to reduce their vulnerability to natural disasters. Moreover, the result of the study provides direction for future studies in the country to reduce loss and enhance structure resiliency against flooding.
Enhancing Anti-Tumorigenic Efficacy of Eugenol in Human Colon Cancer Cells Using Enzyme-Responsive Nanoparticles
Authors: Wijewantha Nisitha , Sane Sanam , Eikanger Morgan , Antony Ryan M. , Potts Rashaun A. , Lang Lydia , Rezvani Khosrow , Sereda Grigoriy
Published: February 2023

This study is focused on the selective delivery and release of the plant-based anticancer compound eugenol (EUG) in colorectal cancer cells (CRC). EUG is an apoptotic and anti-growth compound in diverse malignant tumors, including CRC. However, EUG’s rapid metabolization, excretion, and side effects on normal cells at higher dosages are major limitations of its therapeutic potential. To address this problem, we developed a “smart” enzyme-responsive nanoparticle (eNP) loaded with EUG that exposes tumors to a high level of the drug while keeping its concentration low among healthy cells. We demonstrated that EUG induces apoptosis in CRC cells irrespective of their grades in a dose- and time-dependent manner. EUG significantly decreases cancer cell migration, invasion, and the population of colon cancer stem cells, which are key players in tumor metastasis and drug resistance. The “smart” eNPs–EUG show a high affinity to cancer cells with rapid internalization with no affinity toward normal colon epithelial cells. NPs–EUG enhanced the therapeutic efficacy of EUG measured by a cell viability assay and showed no toxicity effect on normal cells. The development of eNPs–EUG is a promising strategy for innovative anti-metastatic therapeutics.
Association of Dipeptidyl Peptidase-4 Inhibitors Use with Reduced Risk of Hepatocellular Carcinoma in Type 2 Diabetes Patients with Chronic HBV Infection
Authors: Chen Tzu-I , Lee Fu-Jen , Hsu Wan-Lun , Chen Yong-Chen , Chen Mingchih
Published: February 2023

Previous studies have indicated that HBV infection and T2DM are the factors that increase the risk of developing HCC. The experimental evidence has shown that antiglycemic agents may reduce the risk of HCC. However, the effect of dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) on the risk of HCC in T2DM patients with chronic HBV infection remains unclear. In this retrospective cohort study, we extracted patients with T2DM and chronic HBV infection from the National Health Insurance Research Database (NHIRD) in Taiwan. The cases were divided into DPP-4 inhibitors use and non-use groups, according to whether they received DPP-4 inhibitors treatment, and the risk of HCC was compared between the two groups. At the end of the follow-up, approximately 2.33% of DPP-4 inhibitors users had received an HCC diagnosis compared with 3.33% of non-DPP-4 inhibitors users (p < 0.0001). After multivariate adjustment, DPP-4 inhibitors users showed a significant reduction in HCC risk (adjusted hazard ratios (aHRs): 0.53; 95% confidence intervals (CIs): 0.44–0.65). In conclusion, this population-based retrospective cohort study indicated that, in T2DM patients with chronic HBV infection, the use of DPP-4 inhibitors significantly reduced the risk of developing HCC compared with non-DPP-4 inhibitors use.
Patients with Very High Risk of Cardiovascular Adverse Events during Carfilzomib Therapy: Prevention and Management of Events in a Single Center Experience
Authors: Mingrone Giulia , Astarita Anna , Colomba Anna , Catarinella Cinzia , Cesareo Marco , Airale Lorenzo , Paladino Arianna , Leone Dario , Vallelonga Fabrizio , Bringhen Sara , Gay Francesca , Veglio Franco , Milan Alberto
Published: February 2023

Carfilzomib (CFZ) improves the prognosis of multiple myeloma (MM) patients but has shown cardiovascular toxicity. The risk stratification of cardiovascular adverse events (CVAEs) now seems well established, while little is known about the course and management of patients with a high-cardiovascular-risk profile or experiencing CVAEs during therapy. Therefore, we aimed to describe our experience in decision making to support health professionals in selecting the best management strategies to prevent and treat CVAEs. A total of 194 patients with indication to CFZ underwent baseline evaluation of CVAEs risk and were prospectively followed. We propose a novel approach, which includes advanced cardiac imaging testing for patients at high baseline CV risk to rule out clinical conditions that could contraindicate starting CFZ. After baseline evaluation, 19 (9.8%) patients were found at high risk of CVAEs: 13 (6.7%) patients underwent advanced cardiac testing and 3 (1.5%) could not receive CFZ due to CV contraindications. A total of 178 (91.7%) patients started CFZ: 82 (46%) experienced arterial-hypertension-related events and 37 (20.8%) major CVAEs; 19 (10.7%) patients had to discontinue or modify the CFZ dosing regimen. Along with baseline risk stratification, subsequent cardiovascular clinical events and diagnostic follow-up both provided critical data to help identify conditions that could contraindicate the anticancer therapy.
Blood-Based Biomarker Analysis for Predicting Efficacy of Chemoradiotherapy and Durvalumab in Patients with Unresectable Stage III Non-Small Cell Lung Cancer
Authors: Park Cheol-Kyu , Lee Sung-Woo , Cho Hyun-Ju , Oh Hyung-Joo , Kim Young-Chul , Kim Yong-Hyub , Ahn Sung-Ja , Cho Jae-Ho , Oh In-Jae
Published: February 2023

We recruited 50 patients with unresectable stage III NSCLC who received CCRT between March 2020 and March 2021. Durvalumab consolidation (DC) was administered to patients (n = 23) without progression after CCRT and programmed death-ligand 1 (PD-L1) ≥ 1%. Blood samples were collected before (C0) and after CCRT (C1) to calculate PBC counts and analyze CTCs. CTCs, isolated by the CD-PRIMETM system, exhibited EpCAM/CK+/CD45− phenotype in BioViewCCBSTM. At median follow-up of 27.4 months, patients with residual CTC clusters at C1 had worse median PFS than those without a detectable CTC cluster (11.0 vs. 27.8 months, p = 0.032), and this trend was noted only in the DC group (p = 0.034). Patients with high platelets at C1 (PLThi, >252 × 103/µL) had worse median PFS than those with low platelets (PLTlo) (5.9 vs. 17.1 months, p < 0.001). In multivariable analysis, PLThi and residual CTC clusters at C1 were independent risk factors for PFS, and DC group with PLThi and residual CTC clusters at C1 showed the worst median PFS (2.6 months, HR 45.16, p = 0.001), even worse than that of the CCRT alone group with PLThi (5.9 months, HR 15.39, p = 0.001). The comprehensive analysis of CTCs and PBCs before and after CCRT revealed that the clearance of CTC clusters and platelet counts at C1 might be potential biomarkers for predicting survival.
Determinants of Pre-Surgical Treatment in Primary Rectal Cancer: A Population-Based Study
Authors: Imam Israa , Hammarström Klara , Glimelius Bengt
Published: February 2023

When preoperative radiotherapy (RT) is best used in rectal cancer is subject to discussions and guidelines differ. To understand the selection mechanisms, we analysed treatment decisions in all patients diagnosed between 2010–2020 in two Swedish regions (Uppsala with a RT department and Dalarna without). Information on staging and treatment (direct surgery, short-course RT, or combinations of RT/chemotherapy) in the Swedish Colorectal Cancer Registry were used. Staging magnetic resonance imaging (MRI) permitted a division into risk groups, according to national guidelines. Logistic regression explored associations between baseline characteristics and treatment, while Cohen’s kappa tested congruence between clinical and pathologic stages. A total of 1150 patients without synchronous metastases were analysed. Patients from Dalarna were older, had less advanced tumours and were pre-treated less often (52% vs. 63%, p < 0.001). All MRI characteristics (T-/N-stage, MRF, EMVI) and tumour levels were important for treatment choice. Age affected if chemotherapy was added. The correlation between clinical and pathological T-stage was fair/moderate and poor for N-stage. The MRI-based risk grouping influenced treatment choice the most. Since the risk grouping was modified to diminish the pre-treated proportion, fewer patients were irradiated with time. MRI staging is far from optimal. A stronger wish to decrease irradiation may explain why fewer patients from Dalarna were irradiated, but inequality in health care cannot be ruled out.
Sensitive Detection of Cell-Free Tumour DNA Using Optimised Targeted Sequencing Can Predict Prognosis in Gastro-Oesophageal Cancer
Authors: Wallander Karin , Haider Zahra , Jeggari Ashwini , Foroughi-Asl Hassan , Gellerbring Anna , Lyander Anna , Chozhan Athithyan , Cuba Gyllensten Ollanta , Hägglund Moa , Wirta Valtteri , Nordenskjöld Magnus , Lindblad Mats , Tham Emma
Published: February 2023

In this longitudinal study, cell-free tumour DNA (a liquid biopsy) from plasma was explored as a prognostic biomarker for gastro-oesophageal cancer. Both tumour-informed and tumour-agnostic approaches for plasma variant filtering were evaluated in 47 participants. This was possible through sequencing of DNA from tissue biopsies from all participants and cell-free DNA from plasma sampled before and after surgery (n = 42), as well as DNA from white blood cells (n = 21) using a custom gene panel with and without unique molecular identifiers (UMIs). A subset of the plasma samples (n = 12) was also assayed with targeted droplet digital PCR (ddPCR). In 17/31 (55%) diagnostic plasma samples, tissue-verified cancer-associated variants could be detected by the gene panel. In the tumour-agnostic approach, 26 participants (59%) had cancer-associated variants, and UMIs were necessary to filter the true variants from the technical artefacts. Additionally, clonal haematopoietic variants could be excluded using the matched white blood cells or follow-up plasma samples. ddPCR detected its targets in 10/12 (83%) and provided an ultra-sensitive method for follow-up. Detectable cancer-associated variants in plasma correlated to a shorter overall survival and shorter time to progression, with a significant correlation for the tumour-informed approaches. In summary, liquid biopsy gene panel sequencing using a tumour-agnostic approach can be applied to all patients regardless of the presence of a tissue biopsy, although this requires UMIs and the exclusion of clonal haematopoietic variants. However, if sequencing data from tumour biopsies are available, a tumour-informed approach improves the value of cell-free tumour DNA as a negative prognostic biomarker in gastro-oesophageal cancer patients.
Clinical Significance of Tumour-Infiltrating B Lymphocytes (TIL-Bs) in Breast Cancer: A Systematic Literature Review
Authors: Lam Brian M. , Verrill Clare
Published: February 2023

Although T lymphocytes have been considered the major players in the tumour microenvironment to induce tumour regression and contribute to anti-tumour immunity, much less is known about the role of tumour-infiltrating B lymphocytes (TIL-Bs) in solid malignancies, particularly in breast cancer, which has been regarded as heterogeneous and much less immunogenic compared to other common tumours like melanoma, colorectal cancer and non-small cell lung cancer. Such paucity of research could translate to limited opportunities for this most common type of cancer in the UK to join the immunotherapy efforts in this era of precision medicine. Here, we provide a systematic literature review assessing the clinical significance of TIL-Bs in breast cancer. Articles published between January 2000 and April 2022 were retrieved via an electronic search of two databases (PubMed and Embase) and screened against pre-specified eligibility criteria. The majority of studies reported favourable prognostic and predictive roles of TIL-Bs, indicating that they could have a profound impact on the clinical outcome of breast cancer. Further studies are, however, needed to better define the functional role of B cell subpopulations and to discover ways to harness this intrinsic mechanism in the fight against breast cancer.
Mass Spectrometry-Based Biomarkers to Detect Prostate Cancer: A Multicentric Study Based on Non-Invasive Urine Collection without Prior Digital Rectal Examination
Authors: Frantzi Maria , Culig Zoran , Heidegger Isabel , Mokou Marika , Latosinska Agnieszka , Roesch Marie C. , Merseburger Axel S. , Makridakis Manousos , Vlahou Antonia , Blanca-Pedregosa Ana , Carrasco-Valiente Julia , Mischak Harald , Gomez-Gomez Enrique
Published: February 2023

(1) Background: Prostate cancer (PCa) is the most frequently diagnosed cancer in men. Wide application of prostate specific antigen test has historically led to over-treatment, starting from excessive biopsies. Risk calculators based on molecular and clinical variables can be of value to determine the risk of PCa and as such, reduce unnecessary and invasive biopsies. Urinary molecular studies have been mostly focusing on sampling after initial intervention (digital rectal examination and/or prostate massage). (2) Methods: Building on previous proteomics studies, in this manuscript, we aimed at developing a biomarker model for PCa detection based on urine sampling without prior intervention. Capillary electrophoresis coupled to mass spectrometry was applied to acquire proteomics profiles from 970 patients from two different clinical centers. (3) Results: A case-control comparison was performed in a training set of 413 patients and 181 significant peptides were subsequently combined by a support vector machine algorithm. Independent validation was initially performed in 272 negative for PCa and 138 biopsy-confirmed PCa, resulting in an AUC of 0.81, outperforming current standards, while a second validation phase included 147 PCa patients. (4) Conclusions: This multi-dimensional biomarker model holds promise to improve the current diagnosis of PCa, by guiding invasive biopsies.
CTTN Overexpression Confers Cancer Stem Cell-like Properties and Trastuzumab Resistance via DKK-1/WNT Signaling in HER2 Positive Breast Cancer
Authors: Moon So-Jeong , Choi Hyung-Jun , Kye Young-Hyeon , Jeong Ga-Young , Kim Hyung-Yong , Myung Jae-Kyung , Kong Gu
Published: February 2023

Background: Despite the therapeutic success of trastuzumab, HER2 positive (HER2+) breast cancer patients continue to face significant difficulties due to innate or acquired drug resistance. In this study we explored the potential role of CTTN in inducing trastuzumab resistance of HER2+ breast cancers. Methods: Genetic changes of CTTN and survival of HER2+ breast cancer patients were analyzed in multiple breast cancer patient cohorts (METABRIC, TCGA, Kaplan-Meier (KM) plotter, and Hanyang University cohort). The effect of CTTN on cancer stem cell activity was assessed using the tumorsphere formation, ALDEFLUOR assay, and by in vivo xenograft experiments. CTTN-induced trastuzumab resistance was assessed by the sulforhodamine B (SRB) assay, colony formation assays, and in vivo xenograft model. RNA-seq analysis was used to clarify the mechanism of trastuzumab resistance conferred by CTTN. Results: Survival analysis indicated that CTTN overexpression is related to a poor prognosis in HER2+ breast cancers (OS, p = 0.05 in the Hanyang University cohort; OS, p = 0.0014 in KM plotter; OS, p = 0.008 and DFS, p = 0.010 in METABRIC). CTTN overexpression-induced cancer stem cell-like characteristics in experiments of tumorsphere formation, ALDEFLUOR assays, and in vivo limiting dilution assays. CTTN overexpression resulted in trastuzumab resistance in SRB, colony formation assays, and in vivo xenograft models. Mechanistically, the mRNA and protein levels of DKK-1, a Wnt antagonist, were downregulated by CTTN. Treatment of the β-catenin/TCF inhibitor reversed CTTN-induced cancer stem cell-like properties in vitro. Combination treatment with trastuzumab and β-catenin/TCF inhibitor overcame trastuzumab resistance conferred by CTTN overexpression in in vitro colony formation assays. Conclusions: CTTN activates DKK-1/Wnt/β-catenin signaling to induce trastuzumab resistance. We propose that CTTN is a novel biomarker indicating a poor prognosis and a possible therapeutic target for overcoming trastuzumab resistance.
Current Status of Lymphangiogenesis: Molecular Mechanism, Immune Tolerance, and Application Prospect
Authors: Deng Hongyang , Zhang Jiaxing , Wu Fahong , Wei Fengxian , Han Wei , Xu Xiaodong , Zhang Youcheng
Published: February 2023

The lymphatic system is a channel for fluid transport and cell migration, but it has always been controversial in promoting and suppressing cancer. VEGFC/VEGFR3 signaling has long been recognized as a major molecular driver of lymphangiogenesis. However, many studies have shown that the neural network of lymphatic signaling is complex. Lymphatic vessels have been found to play an essential role in the immune regulation of tumor metastasis and cardiac repair. This review describes the effects of lipid metabolism, extracellular vesicles, and flow shear forces on lymphangiogenesis. Moreover, the pro-tumor immune tolerance function of lymphatic vessels is discussed, and the tasks of meningeal lymphatic vessels and cardiac lymphatic vessels in diseases are further discussed. Finally, the value of conversion therapy targeting the lymphatic system is introduced from the perspective of immunotherapy and pro-lymphatic biomaterials for lymphangiogenesis.
Evidence for Choosing Qigong as an Integrated Intervention in Cancer Care: An Umbrella Review
Authors: Mazzocco Ketti , Milani Alessandra , Ciccarelli Chiara , Marzorati Chiara , Pravettoni Gabriella
Published: February 2023

Cancer is the second leading cause of noncommunicable disease death, with an increasing incidence. Qigong practice can moderate non-intrinsic, modifiable risk factors that act on the stress response using physical movements, breathing, and focused attention. The purpose of this umbrella review is to provide a concise summary to facilitate an evidence-based decision to integrate Qigong into cancer patients’ care. Relevant systematic reviews and meta-analyses were identified and retrieved from the JBI database, Cochrane Library, PubMed, Embase, and CINAHL. Of all of the studies assessed, none found evidence of a risk to cancer patients, indicating that Qigong is a safe practice that can be used even by frail patients. The overall quality of life, cancer-related fatigue, and cognitive impairment were improved by Qigong. Different Qigong programs have different impacts on sleep quality and gastrointestinal problems, suggesting that longer practice sessions are required to achieve improvements. To maintain Qigong’s effectiveness, an ordinary practice is essential, or such effectiveness will wear off. The use of biological markers in efficacy assessments needs to be more systematically studied. However, positive WBC, RBC, and CRP trends in Qigong practitioners are evident. Higher-quality clinical studies are necessary to measure variables more closely related to Qigong functioning and consider cancer’s multifactorial nature.
Photodynamic Light-Triggered Release of Curcumin from Hierarchical FAU Zeolite
Authors: Musielak Ewelina , Feliczak-Guzik Agnieszka , Jaroniec Mietek , Nowak Izabela
Published: February 2023

Photodynamic therapy (PDT) is a method used in the treatment of various diseases and represents a promising alternative to classical active substance release methods. According to the United States National Institute of Health, this therapy exploits the health-promoting potential of active substances, referred to as “photosensitizers”, and radiation of specific energy. Curcumin is a natural “photosensitizer” that exhibits anti-inflammatory, antioxidant, and anti-cancer effects. Despite the novelty and innovation of PDT, the method is limited by the difficulty of using “photosensitizers” such as curcumin because of its low solubility in water, which hinders the clinical application of this technique. The use of a “photosensitizer” along with suitable carriers such as hierarchical zeolites is a potential strategy to offset this difficulty. Therefore, the objective of this study was to develop the photodynamic release of curcumin from hierarchical zeolites using the classical open-circuit release method and a novel closed-circuit release technique involving light of different wavelengths. Based on the obtained data, it was possible to unequivocally state that the speed and efficiency of curcumin release from the zeolite carrier is influenced by light with a wavelength in the range of 430–525 nm (blue-cyan-green). As much as 53.24% of the active substance was released upon light exposure.
MnO2 Doped with Ag Nanoparticles and Their Applications in Antimicrobial and Photocatalytic Reactions
Authors: Anguraj G. , Ashok Kumar R. , Inmozhi C. , Uthrakumar R. , Elshikh Mohamed S. , Almutairi Saeedah Musaed , Kaviyarasu K.
Published: February 2023

A wide range of nanoparticles have been produced for photocatalysis applications. Nonetheless, degrading organic dyes requires nanoparticles that are efficient and excellent. As a photocatalyst, pure manganese oxide (MnO2) was prepared via a sol–gel method using silver (Ag) nanoparticles of transition metal oxide. In addition to X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX), the crystal structure and elemental composition were analysed. According to XRD data, the transition metal of MnO2 oxide is highly pure and has a small crystallite size. The presence of functional groups was confirmed and clarified using Fourier-transform infrared spectra (FTIR). By irradiating the transition pure and doped MnO2 photocatalysts with visible light, the UV-vis, μ-Raman, and surface areas were determined. As a result, of using the photocatalysts with aqueous methylene blue (MB) solutions under visible light irradiation, the MnO2 doped with Ag nanoparticles demonstrated high degradation efficiencies and were utilised to establish heterogeneous photocatalysis dominance. In this paper, we demonstrate that the photocatalytic efficiency of transition metal oxides is exclusively determined by the particle size and surface area of nano-sized materials. Due to their high surface charge ratio and different surface orientations, have the highest photocatalytic efficiency. Generally, MnO2 doped with Ag nanoparticles is resistant to bacteria of both Gram-positive and Gram-negative types (B. sublittus and Escherichia coli). There is still a need for more research to be performed on reducing the toxicity of metal and metal oxide nanoparticles so that they can be used as an effective alternative to antibiotics and disinfectants, particularly for biomedical applications.
A Three-Dimensional Engineered Cardiac In Vitro Model: Controlled Alignment of Cardiomyocytes in 3D Microphysiological Systems
Authors: Navaee Fatemeh , Khornian Niloofar , Longet David , Heub Sarah , Boder-Pasche Stephanie , Weder Gilles , Kleger Alexander , Renaud Philippe , Braschler Thomas
Published: February 2023

Cardiomyocyte alignment in myocardium tissue plays a significant role in the physiological, electrical, and mechanical functions of the myocardium. It remains, however, difficult to align cardiac cells in a 3D in vitro heart model. This paper proposes a simple method to align cells using microfabricated Polydimethylsiloxane (PDMS) grooves with large dimensions (of up to 350 µm in width), similar to the dimensions of trabeculae carneae, the smallest functional unit of the myocardium. Two cell groups were used in this work; first, H9c2 cells in combination with Nor10 cells for proof of concept, and second, neonatal cardiac cells to investigate the functionality of the 3D model. This model compared the patterned and nonpatterned 3D constructs, as well as the 2D cell cultures, with and without patterns. In addition to alignment, we assessed the functionality of our proposed 3D model by comparing beating rates between aligned and non-aligned structures. In order to assess the practicality of the model, the 3D aligned structures should be demonstrated to be detachable and alignable. This evaluation is crucial to the use of this 3D functional model in future studies related to drug screening, building blocks for tissue engineering, and as a heart-on-chip by integrating microfluidics.
Pan-Genomic Regulation of Gene Expression in Normal and Pathological Human Placentas
Authors: Apicella Clara , Ruano Camino S. M. , Thilaganathan Basky , Khalil Asma , Giorgione Veronica , Gascoin Géraldine , Marcellin Louis , Gaspar Cassandra , Jacques Sébastien , Murdoch Colin E. , Miralles Francisco , Méhats Céline , Vaiman Daniel
Published: February 2023

In this study, we attempted to find genetic variants affecting gene expression (eQTL = expression Quantitative Trait Loci) in the human placenta in normal and pathological situations. The analysis of gene expression in placental diseases (Pre-eclampsia and Intra-Uterine Growth Restriction) is hindered by the fact that diseased placental tissue samples are generally taken at earlier gestations compared to control samples. The difference in gestational age is considered a major confounding factor in the transcriptome regulation of the placenta. To alleviate this significant problem, we propose here a novel approach to pinpoint disease-specific cis-eQTLs. By statistical correction for gestational age at sampling as well as other confounding/surrogate variables systematically searched and identified, we found 43 e-genes for which proximal SNPs influence expression level. Then, we performed the analysis again, removing the disease status from the covariates, and we identified 54 e-genes, 16 of which are identified de novo and, thus, possibly related to placental disease. We found a highly significant overlap with previous studies for the list of 43 e-genes, validating our methodology and findings. Among the 16 disease-specific e-genes, several are intrinsic to trophoblast biology and, therefore, constitute novel targets of interest to better characterize placental pathology and its varied clinical consequences. The approach that we used may also be applied to the study of other human diseases where confounding factors have hampered a better understanding of the pathology.
Controlling Microenvironments with Organs-on-Chips for Osteoarthritis Modelling
Authors: Ong Louis Jun Ye , Fan Xiwei , Rujia Sun Antonia , Mei Lin , Toh Yi-Chin , Prasadam Indira
Published: February 2023

Osteoarthritis (OA) remains a prevalent disease affecting more than 20% of the global population, resulting in morbidity and lower quality of life for patients. The study of OA pathophysiology remains predominantly in animal models due to the complexities of mimicking the physiological environment surrounding the joint tissue. Recent development in microfluidic organ-on-chip (OoC) systems have demonstrated various techniques to mimic and modulate tissue physiological environments. Adaptations of these techniques have demonstrated success in capturing a joint tissue’s tissue physiology for studying the mechanism of OA. Adapting these techniques and strategies can help create human-specific in vitro models that recapitulate the cellular processes involved in OA. This review aims to comprehensively summarise various demonstrations of microfluidic platforms in mimicking joint microenvironments for future platform design iterations.