bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Randomness in the Rock-Paper-Scissors Game
Authors: Komai Takahiro , Kurokawa Hiroaki , Kim Song-Ju
Published: November 2022

In this study, we investigated the human capacity to generate randomness in decision-making processes using the rock-paper-scissors (RPS) game. The randomness of the time series was evaluated using the time-series data of RPS moves made by 500 subjects who played 50 consecutive RPS games. The indices used for evaluation were the Lempel–Ziv complexity and a determinism index obtained from a recurrence plot, and these indicators represent the complexity and determinism of the time series, respectively. The acquired human RPS time-series data were compared to a pseudorandom RPS sequence generated by the Mersenne Twister and the RPS time series generated by the RPS game’s strategy learned using the human RPS time series acquired via genetic programming. The results exhibited clear differences in randomness among the pseudorandom number series, the human-generated series, and the AI-generated series.
Flow Characteristics of Fibrous Gas Diffusion Layers Using Machine Learning Methods
Authors: Froning Dieter , Wirtz Jannik , Hoppe Eugen , Lehnert Werner
Published: November 2022

The material characteristics of gas diffusion layers are relevant for the efficient operation of polymer electrolyte fuel cells. The current state-of-the-art calculates these using transport simulations based on their micro-structures, either reconstructed or generated by means of stochastic geometry models. Such transport simulations often require high computational resources. To support material characterization using artificial-intelligence-based methods, in this study, a convolutional neural network was developed. It was trained with results from previous transport simulations and validated using five-fold cross-validation. The neural network enables the permeability of paper-type gas diffusion layers to be predicted. A stochastic arrangement of the fibers, four types of binder distributions, and compression of up to 50% are also considered. The binder type and compression level were features inherent to the material but were not the subject of the training. In this regard, they can be seen as features hidden from the training process. Nevertheless, these characteristics were reproduced with the proposed machine learning model. With a trained machine learning model, the prediction of permeability can be performed on a standard computer.
Wheat Ear Detection Algorithm Based on Improved YOLOv4
Authors: Zhao Fengkui , Xu Lizhang , Lv Liya , Zhang Yong
Published: November 2022

The continuously growing population requires improving the efficiency of agricultural production. Wheat is one of the most wildly cultivated crops. Intelligent wheat ear monitoring is essential for crop management and crop yield prediction. Although a variety of methods are utilized to detect or count wheat ears, there are still some challenges both from the data acquisition process and the wheat itself. In this study, a computer vision methodology based on YOLOv4 to detect wheat ears is proposed. A large receptive field allows viewing objects globally and increases the connections between the image points and the final activation. Specifically, in order to enhance the receptive field, additional Spatial Pyramid Pooling (SPP) blocks are added to YOLOv4 at the feature fusion section to extract multi-scale features. Pictures of wheat ears taken at different growth stages from two different datasets are used to train the model. The performance of the proposed methodology was evaluated using various metrics. The Average Precision (AP) was 95.16% and 97.96% for the two datasets, respectively. By fitting the detected wheat ear numbers and true wheat ear numbers, the R2 value was 0.973. The results show that the proposed method outperforms YOLOv4 in wheat ear detection. It indicates that the proposed method provides a technical reference for agricultural intelligence.
Climate Change Trends in a European Coastal Metropolitan Area: Rainfall, Temperature, and Extreme Events (1864–2021)
Authors: Espinosa Luis Angel , Portela Maria Manuela , Matos José Pedro , Gharbia Salem
Published: November 2022

This paper summarises an updated climate change trends analysis—developed for the period from 1 October 1864 to 30 September 2021 within the scope of a Horizon 2020-funded project to increase climate resilience in European coastal cities—for a representative site of the Lisbon Metropolitan Area (Portugal). By using long ground-based daily records of rainfall and surface temperature at the Lisboa-Geofísico climatological station, the analysis aimed to identify (i) long-term and recent climate trends in rainfall and temperature, (ii) changes in extreme rainfalls, heatwaves, and droughts, and (iii) possible effects of the coupled changes of minimum and maximum daily temperatures (Tmin and Tmax, respectively) on drought development based on the diurnal temperature range (DTR) indicator. To detect these trends and quantify their magnitude, the Mann−Kendall and Sen’s slope estimator tests were implemented. The analysis of the mean annual temperatures indicated that the study area has warmed ∼1.91 °C through the 157 analysed years. Results evidenced statistically significant upward trends in both Tmin and Tmax, and in the number of Tmax heatwave days. In what concerns the extreme hydrological events, the analysis of annual maximum rainfall series and peaks-over-threshold (POT) techniques showed more frequent and intense events in recent years, reaching up to ∼120.0 mm in a single day. With regard to drought, the study proved that the characterisation based on the commonly used standardised precipitation index (SPI) might differ from that based on the standardised precipitation evapotranspiration index (SPEI), as the latter can take into account not only rainfall but also temperature, an important trigger for the development of drought. According to the SPEI index, severe and extreme drought conditions have been more frequent in the last 60 years than in any other recorded period. Finally, a decreasing DTR trend towards the present was found to influence evapotranspiration rates and thus drought characteristics.
Atmospheric Aerosol Outbreak over Nicosia, Cyprus, in April 2019: Case Study
Authors: Yukhymchuk Yuliia , Milinevsky Gennadi , Syniavskyi Ivan , Popovici Ioana , Unga Florin , Sciare Jean , Marenco Franco , Pikridas Michael , Goloub Philippe
Published: November 2022

This paper aims to analyze the significant changes in atmospheric aerosol characteristics during the extreme aerosol outbreak event in April 2019 in the atmosphere over Cyprus in the Eastern Mediterranean. We study the aerosol optical depth (AOD), Ångström exponent (AE), single-scattering albedo, refractive index, size, and vertical distribution of aerosol particles during the event of intense aerosol advection in detail. For this purpose, we used the ground-based observations of the sun-photometer AERONET Nicosia station, lidar measurements, and back trajectories of air movements calculated using the Hybrid Single-Particle Lagrangian Integrated Trajectory Model (HYSPLIT). To compare with background aerosol load conditions during the year, the available data of AOD and AE were used from the observations at the Nicosia AERONET site in the 2015–2022 period. On 23–25 April 2019, strong aerosol advection over Nicosia was detected according to lidar and sun-photometer observations. On 25 April 2019, the day with the largest aerosol contamination, the AOD value exceeded 0.9 at λ = 500 nm. Analysis of the optical and microphysical characteristics during the extreme event supported that the aerosol advection consists of mainly Saharan dust particles. This assumption was confirmed by the AOD versus AE variations, single-scattering albedo, refractive index, and size distribution retrievals, as well as lidar data and HYSPLIT backward trajectories, where air masses containing dust particles came mostly from North Africa. The analysis shows that the April 2019 event was one of the strongest aerosol surges that regularly take place in springtime in the atmosphere over Cyprus. The noticeable reduction in the effective radiative forcing caused by increasing aerosol amount during the aerosol dust outbreak was revealed.
Impact of the Destination Weather Conditions on Decision and Complaint Behavior of Guests Who Booked Vacation Rentals
Authors: Zeiss Harald , Graw Kathrin , Matzarakis Andreas
Published: November 2022

Climate and weather conditions at a destination influence the decision regarding what season and which location tourists might travel to. Assuming that the holiday experiences and satisfaction during their stay are influenced by weather and climate as well, this study investigates the question: does bad weather lead to a higher complaint rate among guests who booked vacation rentals? To answer this question, the complaint behavior and the weather parameters temperature, precipitation, wind speed and humidity are examined. The correlations between weather and complaining behavior are proven using the four-field coefficient. The chi-square four-field test is used to subsequently test independence. As a result, a correlation between the weather parameters and complaints cannot be proven based on the applied methods and used data. The four-field coefficient cannot confirm a correlation, as it is close to zero for all four weather parameters. For further investigations, more complaint data are required to obtain more significant results.
The Activity of Polyhomoarginine against Acanthamoeba castellanii
Authors: Peguda Hari Kumar , Lakshminarayanan Rajamani , Carnt Nicole A. , Gu Zi , Willcox Mark D. P.
Published: November 2022

Arginine-rich peptides can have broad-spectrum anti-bacterial and anti-fungal activities. Polyhomoarginine consists of highly cationic residues which can act on the negatively charged microbial cell membranes. Acanthamoeba is a free-living protozoan known to cause a rare corneal infection which is difficult to diagnose and treat. This study evaluated the activity of the polyhomoarginines against Acanthamoeba castellanii. Acanthamoeba amoebicidal, amoebistatic, encystation and excystment assays were performed using protocols described in the literature. The activity of polyhomoarginines (PHAs) of different lengths (10 to 400 residues) was measured against the trophozoites and cysts of Acanthamoeba castellanii ATCC30868 in concentrations ranging from 0.93 μM to 15 μM. Data were represented as mean ± SE and analysed using one-way ANOVA. Overall, PHAs demonstrated good anti-acanthamoeba activity against both trophozoites and cysts. PHA 30 reduced the number of viable trophozoites by 99%, inhibited the formation of cysts by 96% and the emergence of trophozoites from cysts by 67% at 3.75 μM. PHA 10 was similarly active, but at a slightly higher concentration of 15 μM, reducing the numbers of viable trophozoites by 98%, inhibiting cyst formation by 84% and preventing the emergence of trophozoites from cysts by 99%. At their greatest anti-amoeba concentrations, PHA 10 gave only 8% haemolysis at 15 μM while PHA 30 gave <40 % haemolysis at 3.75 μM. Polyhomoarginine 10 showed excellent anti-amoebic activity against both forms of Acanthamoeba castellanii and was non-toxic at its most active concentrations. This implies that polyhomoarginines can be developed into a potential therapeutic agent for Acanthamoeba keratitis. However, there is a need to carry out further pre-clinical and then in vivo experiments in the AK animal model.
KRS-Net: A Classification Approach Based on Deep Learning for Koi with High Similarity
Authors: Zheng Youliang , Deng Limiao , Lin Qi , Xu Wenkai , Wang Feng , Li Juan
Published: November 2022

As the traditional manual classification method has some shortcomings, including high subjectivity, low efficiency, and high misclassification rate, we studied an approach for classifying koi varieties. The main contributions of this study are twofold: (1) a dataset was established for thirteen kinds of koi; (2) a classification problem with high similarity was designed for underwater animals, and a KRS-Net classification network was constructed based on deep learning, which could solve the problem of low accuracy for some varieties that are highly similar. The test experiment of KRS-Net was carried out on the established dataset, and the results were compared with those of five mainstream classification networks (AlexNet, VGG16, GoogLeNet, ResNet101, and DenseNet201). The experimental results showed that the classification test accuracy of KRS-Net reached 97.90% for koi, which is better than those of the comparison networks. The main advantages of the proposed approach include reduced number of parameters and improved accuracy. This study provides an effective approach for the intelligent classification of koi, and it has guiding significance for the classification of other organisms with high similarity among classes. The proposed approach can be applied to some other tasks, such as screening, breeding, and grade sorting.
Role of Senescent Cells in Cutaneous Wound Healing
Authors: Andrade Allison M. , Sun Mingda , Gasek Nathan S. , Hargis Geneva R. , Sharafieh Roshanak , Xu Ming
Published: November 2022

Cellular senescence has gained increasing attention in the field of aging research. Senescent cells have been implicated in biological aging processes, tumorigenesis, development, and wound repair amongst other processes and pathologies. Recent findings reveal that senescent cells can both promote and inhibit cutaneous wound healing processes. Relating senescent cells in acute and chronic wounds will help to clarify their role in wound healing processes and inform our understanding of senescent cell heterogeneity. To clarify this apparent contradiction and guide future research and therapeutic development, we will review the rapidly growing field of cellular senescence and its role in wound healing biology.
Diabetic Hearts Exhibit Global DNA Hypermethylation That Alter the Mitochondrial Functional Genes to Enhance the Sensitivity of the Heart to Ischemia Reperfusion Injury
Authors: Boovarahan Sri Rahavi , Chellappan David Raj , Ali Nemat , AlAsmari Abdullah F. , Waseem Mohammad , Alabdulrahim Abdullah Saad , Alzahrani Ziyad Ali , Kurian Gino A.
Published: November 2022

A recent study has shown that DNA hypermethylation can promote ischemia reperfusion (I/R) injury by regulating the mitochondrial function. Diabetes mellitus (DM) is reported to induce DNA hypermethylation, but whether this prior DNA methylation in DM I/R heart inflicts a beneficial or detrimental effect is not known and is addressed in this study. DM was induced in 6-week-old male Wistar rats with streptozotocin (65 mg/kg b.wt). After 24 weeks on a normal diet, I/R was induced in rat heart using a Langendorff perfusion system and analyzed the myocardium for different parameters to measure hemodynamics, infarct size, DNA methylation and mitochondrial function. Diabetic heart exhibited DNA hypermethylation of 39% compared to the control, along with DNMT expression elevated by 41%. I/R induction in diabetic heart promoted further DNA hypermethylation (24%) with aggravated infarct size (21%) and reduced the cardiac rate pressure product (43%) from I/R heart. Importantly, diabetic I/R hearts also experienced a decline in the mitochondrial copy number (60%); downregulation in the expression of mitochondrial bioenergetics (ND1, ND2, ND3, ND4, ND5, ND6) and mitofusion (MFN1, MFN2) genes and the upregulation of mitophagy (PINK, PARKIN, OPTN) and mitofission (MFF, DNM1, FIS1) genes that reduce the dp/dt contribute to the contractile dysfunction in DM I/R hearts. Besides, a negative correlation was obtained between mitochondrial PGC1α, POLGA, TFAM genes and DNA hypermethylation in DM I/R hearts. Based on the above data, the elevated global DNA methylation level in diabetic I/R rat hearts deteriorated the mitochondrial function by downregulating the expression of POLGA, TFAM and PGC1α genes and negatively contributed to I/R-associated increased infarct size and altered hemodynamics.
A High-Fat and High-Carbohydrate Diet Promotes Reminiscent Hallmarks of an Aging Ovary in the Rabbit Model
Authors: Díaz-Hernández Verónica , Montaño Luis M. , Caldelas Ivette , Marmolejo-Valencia Alejandro
Published: November 2022

The primary definition of ovarian aging refers to the loss of follicles. Moreover, the aging of the microenvironment in ovaries, specifically affecting the follicles, may reveal deterioration with advancing age. Besides aging, metabolic disorders associated with hypercaloric diets may affect ovarian health and manifest characteristics associated with premature aging. In this study, we used 10-week-old chinchilla rabbits fed with a high-fat and high-carbohydrate diet (HFCD) until 25 weeks of age to explore hallmarks of reminiscent ovarian aging. The HFCD diet appeared to affect the ovarian reserve, reflected in a significant decrease in primordial follicles. Likewise, Sudan black stain detection revealed substantial differences in the deposits of lipofuscin in the interstitial glands of HFCD-fed rabbits compared to controls, constituting a “hallmark” of aging. The HFCD showed no induced changes in the expression of SOD 2 in the interstitial gland; however, surface epithelium cells were greater expressed. Besides this, the HFCD induced nuclear translocation of NF-ΚΒ p65 factor transcription in surface epithelium cells. We conclude that an HFCD induces a greater accumulation of senescence cells in the interstitial gland, promoting characteristics reminiscent of ovarian aging. However, the activation mechanism of NF-KB caused by an HFCD, which may be stress-responsive and generated by the interstitial gland, requires further study.
PDMS/PVDF Electrospinning Membranes for Water-in-Oil Emulsion Separation and UV Protection
Authors: Li Jie , Li Yushan , Lu Yiyi , Shi Wentian , Tian Huafeng
Published: November 2022

With industry development, the separation of oily wastewater is becoming more critical. Inspired by organisms such as lotus leaves, biomimetic superhydrophobic surfaces with micro-nano structures have shown great potential in this regard. In this work, PDMS/PVDF oil–water separation membranes with designed microstructures were prepared by electrospinning technology. The membrane-forming effect of electrospinning with different ratios of PDMS and PVDF was studied. The study found that membranes with high PDMS content were more likely to form microspheres, and PDMS tended to concentrate on the microspheres. The results also showed that the microspheres would bring better hydrophobicity to the membrane. When the ratio of PDMS to PVDF is 1:2, the membrane has a water contact angle of up to 150° and an oil contact angle of 0°. At this ratio, the separation efficiency of the membrane for the water-in-oil emulsion is 98.7%, and it can still maintain more than 98% after ten separation cycles, which is a good candidate for oil–water separation. Furthermore, microspheres enable the membrane to achieve macroscopic uniformity and microscopic phase separation so that the membranes have both good elongation and fracture strength. In addition, the PDMS/PVDF membranes also exhibit excellent UV resistance, and their UV protection factor is greater than 185, making them a potential UV protective material.
A Mixed Visual Encoding Model Based on the Larger-Scale Receptive Field for Human Brain Activity
Authors: Ma Shuxiao , Wang Linyuan , Chen Panpan , Qin Ruoxi , Hou Libin , Yan Bin
Published: November 2022

Research on visual encoding models for functional magnetic resonance imaging derived from deep neural networks, especially CNN (e.g., VGG16), has been developed. However, CNNs typically use smaller kernel sizes (e.g., 3 × 3) for feature extraction in visual encoding models. Although the receptive field size of CNN can be enlarged by increasing the network depth or subsampling, it is limited by the small size of the convolution kernel, leading to an insufficient receptive field size. In biological research, the size of the neuronal population receptive field of high-level visual encoding regions is usually three to four times that of low-level visual encoding regions. Thus, CNNs with a larger receptive field size align with the biological findings. The RepLKNet model directly expands the convolution kernel size to obtain a larger-scale receptive field. Therefore, this paper proposes a mixed model to replace CNN for feature extraction in visual encoding models. The proposed model mixes RepLKNet and VGG so that the mixed model has a receptive field of different sizes to extract more feature information from the image. The experimental results indicate that the mixed model achieves better encoding performance in multiple regions of the visual cortex than the traditional convolutional model. Also, a larger-scale receptive field should be considered in building visual encoding models so that the convolution network can play a more significant role in visual representations.
Dynamics of Physiological, Biochemical and Psychological Markers during Single Session of Virtual Reality-Based Respiratory Biofeedback Relaxation
Authors: Mazgelytė Eglė , Zagorskaja Julija , Dereškevičiūtė Edita , Petrėnas Tomas , Kaminskas Andrius , Songailienė Jurgita , Utkus Algirdas , Chomentauskas Gintaras , Karčiauskaitė Dovilė
Published: November 2022

Psychological stress exposure is associated with long-lasting health effects including memory problems, depression, aches and pains, eating disorders, and alcohol or drug use. Thus, there is a need to develop effective stress management strategies that are easy to learn and practice. Respiratory biofeedback is an evidence-based stress management technique presenting breathing-related information to help subjects learn specific breathing skills for relaxation. It is suggested that the use of biofeedback techniques in conjunction with virtual reality makes biofeedback training an even more effective tool for stress management. The current study aimed to investigate dynamics of distinct stress indicators before, after, as well as during one brief virtual reality-based respiratory biofeedback session. Thirty-nine healthy volunteers participated in the study. Individuals provided their saliva samples and evaluated their mood status, fatigue, and strain level before and after the session. The subjects’ heart and respiratory rate, heart rate variability, and galvanic skin response measures were recorded during the session. The results showed that after single 12 min relaxation session, there was a significant decrease in salivary cortisol concentration, heart and respiratory rate, as well as decrease in skin conductance values. Self-reported strain, fatigue level, and mood status also significantly improved. VR-based respiratory-biofeedback-assisted relaxation sessions might serve as an effective stress management strategy, as even single session had positive effects on subjects’ autonomic nervous system (ANS) and hypothalamic-pituitary–adrenal (HPA) axis activity, as well as self-reported fatigue, strain level, and mood status.
Image Quality Metrics, Personality Traits, and Subjective Evaluation of Indoor Environment Images
Authors: Wang Yuwei , Durmus Dorukalp
Published: November 2022

Adaptive lighting systems can be designed to detect the spatial characteristics of the visual environment and adjust the light output to increase visual comfort and performance. Such systems would require computational metrics to estimate occupants’ visual perception of indoor environments. This paper describes an experimental study to investigate the relationship between the perceived quality of indoor environments, personality, and computational image quality metrics. Forty participants evaluated the visual preference, clarity, complexity, and colorfulness of 50 images of indoor environments. Twelve image quality metrics (maximum local variation (MLV), spatial frequency slope (α), BRISQUE, entropy (S), ITU spatial information (SI), visual complexity (Rspt), colorfulness (M), root mean square (RMS) contrast, Euler, energy (E), contour, and fractal dimension) were used to estimate participants’ subjective evaluations. While visual clarity, visual complexity, and colorfulness could be estimated using at least one metric, none of the metrics could estimate visual preference. The results indicate that perceived colorfulness is highly correlated with perceived clarity and complexity. Personality traits tested by the 10-item personality inventory (TIPI) did not impact the subjective evaluations of the indoor environmental images. Future studies will explore the impact of target and background luminance on the perceived quality of indoor images.
The Legacy of Lithuanian Urban and Semi-Urban Vernacular Architecture and Possibilities of Its Preservation
Authors: Samalavičius Almantas Liudas , Gabrėnas Arnoldas
Published: November 2022

Interest in vernacular architecture and vernacular buildings has grown significantly during recent decades. Nevertheless, despite the number of important studies that have been proliferating, there is a lot of material in various geographic localities that still requires further scrutiny. Vernacular architecture in the post-Soviet/post-communist space is one such area. In the Lithuanian context, vernacular buildings have been long neglected and marginalized in research projects, even though traditional Lithuanian architecture (previously often referred to as “folk architecture”) has been quite well-researched and remains an object of interest. There are, however, certain particular forms of contemporary vernacular architecture—urban and suburban in particular—that have rarely been scrutinized for numerous reasons. The former suburb of Šnipiškės, now being converted into a new center of the city of Vilnius, is an area where modern housing and office towers co-exist with older vernacular buildings. Having been constructed in different historical periods and socio-cultural contexts, they represent the features of local vernacular architecture as well as certain relations to rural vernacular architecture. As an urban quarter, Šnipiškės is comparable to the kampungs (or urban villages) that exist in Indonesia and some other countries. The peculiarities of vernacular buildings in Šnipiškės are discussed in this article. The other type of vernacular discussed is the suburban “collective garden” house, largely constructed during the Soviet period when city-dwellers were allowed to maintain small pieces of land for individual semi-urban farming and erect simple structures on their sites. After the fall of the regime, this type of house underwent numerous changes: some of them, designed with the help of architectural professionals, were eventually reshaped and reconstructed by their owners according to the “Do it yourself” principle. Both types represent a culture of contemporary urban and semi-urban vernacular architecture. As cities in the eastern part of Europe, including Lithuania, are undergoing rapid and often heedless transformations, understanding the value of vernacular buildings and preserving some legacy of surviving vernacular structures of various types is culturally important.
Predicting the Early Response to Neoadjuvant Therapy with Breast MR Morphological, Functional and Relaxometry Features—A Pilot Study
Authors: Pintican Roxana , Fechete Radu , Boca Bianca , Cambrea Madalina , Leonte Tiberiu , Camuescu Oana , Gherman Diana , Bene Ioana , Ciule Larisa Dorina , Ciortea Cristiana Augusta , Dudea Sorin Marian , Ciurea Anca Ileana
Published: November 2022

Aim: To evaluate the role of MR relaxometry and derived proton density analysis in the prediction of early treatment response after two cycles of neoadjuvant therapy (NAT), in patients with breast cancer. Methods: This was a prospective study that included 59 patients with breast cancer, who underwent breast MRI prior (MRI1) and after two cycles of NAT (MRI2). The MRI1 included a sequential acquisition with five different TE’s (50, 100, 150, 200 and 250 ms) and a TR of 5000 ms. Post-processing was used to obtain the T2 relaxometry map from the MR acquisition. The tumor was delineated and seven relaxometry and proton density parameters were extracted. Additional histopathology data, T2 features and ADC were included. The response to NAT was reported based on the MRI2 as responders: partial response (>30% decreased size) and complete response (no visible tumor stable disease (SD); and non-responders: stable disease or progression (>20% increased size). Statistics was done using Medcalc software. Results: There were 50 (79.3%) patients with response and 13 (20.7%) non-responders to NAT. Age, histologic type, “in situ” component, tumor grade, estrogen and progesterone receptors, ki67% proliferation index and HER2 status were not associated with NAT response (all p > 0.05). The nodal status (N) 0 was associated with early response, while N2 was associated with non-response (p = 0.005). The tumor (T) and metastatic (M) stage were not statistically significant associated with response (p > 0.05). The margins, size and ADC values were not associated with NAT response (p-value > 0.05). The T2 min relaxometry value was associated with response (p = 0.017); a cut-off value of 53.58 obtained 86% sensitivity (95% CI 73.3–94.2), 69.23 specificity (95% CI 38.6–90.9), with an AUC = 0.715 (p = 0.038). The combined model (T2 min and N stage) achieved an AUC of 0.826 [95% CI: 0.66–0.90, p-value < 0.001]. Conclusions: MR relaxometry may be a useful tool in predicting early treatment response to NAT in breast cancer patients.
New Challenges Facing Systemic Therapies of Advanced HCC in the Era of Different First-Line Immunotherapy-Based Combinations
Authors: Edeline Julien , Meyer Tim , Blanc Jean-Frédéric , Raoul Jean-Luc
Published: November 2022

The standard of care of first-line systemic therapy for advanced hepatocellular carcinoma (HCC) is currently changing with the results of the IMbrave150 trial which are demonstrating superiority of the atezolizumab-bevacizumab combination over sorafenib, modifying this line of treatment for the first time in over 10 years. Recently, other immunotherapy-based combinations (durvalumab-tremelimumab, lenvatinib-pembrolizumab, cabozantinib-atezolizumab, and camrelizumab-rivoceranib) reported results in phase III studies, and might challenge this new standard of care. This revolution will lead to a considerable change in practice, and highlight challenges for future drug development. In this review, we will, firstly, describe results of the different combinations, and discuss the difficulties in selecting the first-line treatment. We will then present the different recommendations about second-line treatment following the first-line immunotherapy-based combination, discussing the rationale for the differences in existing recommendations. We will finally discuss the challenges for future drug development in advanced HCC.
Characteristics and Outcomes of Patients with Cancer Pain Placed in an Emergency Department Observation Unit
Authors: Krishnamani Pavitra Parimala , Qdaisat Aiham , Wattana Monica Kathleen , Lipe Demis N. , Sandoval Marcelo , Elsayem Ahmed , Cruz Carreras Maria Teresa , Yeung Sai-Ching Jim , Chaftari Patrick S.
Published: November 2022

Pain remains an undertreated complication of cancer, with poor pain control decreasing patients’ quality of life. Traditionally, patients presenting to an emergency department with pain have only had two dispositions available to them: hospitalization or discharge. A third emerging healthcare environment, the emergency department observation unit (EDOU), affords patients access to a hospital’s resources without hospitalization. To define the role of an EDOU in the management of cancer pain, we conducted a retrospective study analyzing patients placed in an EDOU with uncontrolled cancer pain for one year. Patient characteristics were summarized using descriptive statistics and predictors of disposition from the EDOU and were identified with univariate and multivariate analyses. Most patients were discharged home, and discharged patients had low 72-hour revisit and 30-day mortality rates. Significant predictors of hospitalization were initial EDOU pain score (odds ratio (OR) = 1.12; 95% CI 1.06–1.19; p < 0.001) and supportive care (OR = 2.04; 95% CI 1.37–3.04; p < 0.001) or pain service (OR = 2.67; 95% CI 1.63–4.40; p < 0.001) consultations. We concluded that an EDOU appears to be the appropriate venue to care for a subsegment of patients presenting to an emergency department with cancer pain, with patients receiving safe care as well as appropriate consultation and admission when indicated.
Reproductive and Endocrine Outcomes in a Cohort of Danish Women following Auto-Transplantation of Frozen/Thawed Ovarian Tissue from a Single Center
Authors: Colmorn Lotte B. , Pedersen Anette T. , Larsen Elisabeth C. , Hansen Alexandra S. , Rosendahl Mikkel , Andersen Claus Yding , Kristensen Stine G. , Macklon Kirsten T.
Published: November 2022

Ovarian tissue cryopreservation (OTC) is a method of fertility preservation in girls and young women prior to gonadotoxic treatment. It is a safe and promising method to restore fertility. The initial recovery of endocrine function is high, but the longevity of the grafted tissue varies. In this single-center, combined retro- and prospective cohort study, we report the reproductive outcome and hormonal recovery following ovarian tissue transplantation (OTT) and evaluate possible predictors of the chance of pregnancy. The study includes 40 women from eastern Denmark undergoing 53 OTTs between 2003 and 2021. Permission to obtain retrospective data was given by the Danish Patient Safety Authorities and prospective data-collection by informed consent. Initial recovery of endocrine function was seen in 18/19 women with POI, and ongoing function of the grafted tissue in 7/14 two years from OTT. Live birth rate (LBR) was 41%, with 20 children to 39 women trying to conceive. Women who conceived had higher AFC at the time of OTC than women who did not (p ± 0.04). Repeated transplantations were not successful in terms of delivery. Half of all pregnancies were achieved by ART, but PRs were lower after ART than by spontaneous conception. LBRs after OTT are encouraging. Chance of pregnancy after OTT is correlated to ovarian reserve at OTC. Repeated transplantations were not successful in terms of unfulfilled pregnancy wish.
Ashkenazi Jewish and Other White APC I1307K Carriers Are at Higher Risk for Multiple Cancers
Authors: Forkosh Esther , Bergel Michael , Hatchell Kathryn E. , Nielsen Sarah M. , Heald Brandie , Benson Ariel A. , Friedman Eitan , Esplin Edward D. , Katz Lior H.
Published: November 2022

Purpose: APC I1307K has a higher prevalence among Ashkenazi Jews (AJ), and a two-fold increased risk for colorectal cancer (CRC) compared to non-Jewish populations. We assessed CRC and extracolonic malignancies among I1307K carriers from AJ and non-AJ whites (NAW). Methods: We compared the rate of I1307K in cancer patients who underwent germline genetic testing via a multi-gene panel with healthy subjects retrieved from the gnomAD database. Cases undergoing testing were not selected and testing was undertaken through a commercial laboratory. Results: Overall, 586/7624 (7.6%) AJ with cancer carried I1307K compared to 342/4918 (6.9%) in the AJ control group (p = NS). In the NAW, 318/141,673 (0.2%) cancer patients and 73/58,918 (0.1%) controls carried the variant [OR = 1.8, (95% CI 1.41–2.35), p < 0.001]. I1307K in NAW was associated with an increased risk of CRC [OR = 1.95, (95% CI 1.39–2.73), p < 0.01], melanoma [OR = 2.54, (95% CI 1.57–3.98)], breast [females, OR = 1.73, (95% CI 1.18–2.65), p < 0.01], and prostate cancer [males, OR = 2.42, (95% CI 1.45–3.94), p < 0.01]. Among AJ, the variant increased the risk for CRC [OR = 1.67, (95% CI 1.36–2.05), p < 0.001] and renal cancer [OR = 1.64, (95% CI 1.04–2.47)]. AJ men had a higher risk for any cancer [OR = 1.32, (95% CI 1.05–1.66), p < 0.05] and melanoma [OR = 2.04, (95% CI 1.24–3.22); p < 0.05]. Conclusions: This is the most extensive study to date conducted on I1307K carriers, although it is amenable to selection bias. NAW carrying I1307K had a higher risk of any cancer and several specific cancer types, whereas AJ carrying the variant had a risk for only a few select cancers. Our data add to the research base on I1307 carriers concerning future risk management.
The DARC Side of Inflamm-Aging: Duffy Antigen Receptor for Chemokines (DARC/ACKR1) as a Potential Biomarker of Aging, Immunosenescence, and Breast Oncogenesis among High-Risk Subpopulations
Authors: Jinna Nikita , Rida Padmashree , Su Tianyi , Gong Zhihong , Yao Song , LaBarge Mark , Natarajan Rama , Jovanovic-Talisman Tijana , Ambrosone Christine , Seewaldt Victoria
Published: November 2022

The proclivity of certain pre-malignant and pre-invasive breast lesions to progress while others do not continues to perplex clinicians. Clinicians remain at a crossroads with effectively managing the high-risk patient subpopulation owing to the paucity of biomarkers that can adequately risk-stratify and inform clinical decisions that circumvent unnecessary administration of cytotoxic and invasive treatments. The immune system mounts the most important line of defense against tumorigenesis and progression. Unfortunately, this defense declines or “ages” over time—a phenomenon known as immunosenescence. This results in “inflamm-aging” or the excessive infiltration of pro-inflammatory chemokines, which alters the leukocyte composition of the tissue microenvironment, and concomitant immunoediting of these leukocytes to diminish their antitumor immune functions. Collectively, these effects can foster the sequelae of neoplastic transformation and progression. The erythrocyte cell antigen, Duffy antigen receptor for chemokines(DARC/ACKR1), binds and internalizes chemokines to maintain homeostatic levels and modulate leukocyte trafficking. A negative DARC status is highly prevalent among subpopulations of West African genetic ancestry, who are at higher risk of developing breast cancer and disease progression at a younger age. However, the role of DARC in accelerated inflamm-aging and malignant transformation remains underexplored. Herein, we review compelling evidence suggesting that DARC may be protective against inflamm-aging and, therefore, reduce the risk of a high-risk lesion progressing to malignancy. We also discuss evidence supporting that immunotherapeutic intervention—based on DARC status—among high-risk subpopulations may evade malignant transformation and progression. A closer look into this unique role of DARC could glean deeper insight into the immune response profile of individual high-risk patients and their predisposition to progress as well as guide the administration of more “cyto-friendly” immunotherapeutic intervention to potentially “turn back the clock” on inflamm-aging-mediated oncogenesis and progression.
Pregestational Exposure to T. gondii Produces Maternal Antibodies That Recognize Fetal Brain Mimotopes and Induces Neurochemical and Behavioral Dysfunction in the Offspring
Authors: Romero Núñez Eunice , Blanco Ayala Tonali , Vázquez Cervantes Gustavo Ignacio , Roldán-Roldán Gabriel , González Esquivel Dinora Fabiola , Muñiz-Hernández Saé , Salazar Alelí , Méndez Armenta Maricela , Gómez-Manzo Saúl , González-Conchillos Hugo , Luna-Nophal Angélica , Acosta Ramírez Alma Patrica , Pineda Benjamín , Jiménez-Anguiano Anabel , Pérez de la Cruz Verónica
Published: November 2022

The activation of the maternal immune system by a prenatal infection is considered a risk factor for developing psychiatric disorders in the offspring. Toxoplasma gondii is one of the pathogenic infections associated with schizophrenia. Recent studies have shown an association between high levels of IgG anti-T. gondii from mothers and their neonates, with a higher risk of developing schizophrenia. The absence of the parasite and the levels of IgGs found in the early stages of life suggest a transplacental transfer of the anti-T. gondii IgG antibodies, which could bind fetal brain structures by molecular mimicry and induce alterations in neurodevelopment. This study aimed to determine the maternal pathogenic antibodies formation that led to behavioral impairment on the progeny of rats immunized with T. gondii. Female rats were immunized prior to gestation with T. gondii lysate (3 times/once per week). The anti-T. gondii IgG levels were determined in the serum of pregestational exposed females’ previous mating. After this, locomotor activity, cognitive and social tests were performed. Cortical neurotransmitter levels for dopamine and glutamate were evaluated at 60 PND in the progeny of rats immunized before gestation (Pregestational group). The maternal pathogenic antibodies were evidenced by their binding to fetal brain mimotopes in the Pregestational group and the reactivity of the serum containing anti-T. gondii IgG was tested in control fetal brains (non-immunized). These results showed that the Pregestational group presented impairment in short and long-term memory, hypoactivity and alteration in social behavior, which was also associated with a decrease in cortical glutamate and dopamine levels. We also found the IgG antibodies bound to brain mimotopes in fetuses from females immunized with T. gondii, as well as observing a strong reactivity of the serum females immunized for fetal brain structures of fetuses from unimmunized mothers. Our results suggest that the exposure to T. gondii before gestation produced maternal pathogenic antibodies that can recognize fetal brain mimotopes and lead to neurochemical and behavioral alterations in the offspring.
Prevalence of High Blood Pressure in Pediatric Patients with Sleep-Disordered Breathing, Reversibility after Treatment: The KIDS TRIAL Study Protocol
Authors: Castillo-García María , Solano-Pérez Esther , Romero-Peralta Sofía , Viejo-Ayuso María Esther , Silgado-Martínez Laura , Álvarez-Balado Leticia , Mediano San Andrés Rosa , Resano-Barrio Pilar , García-Rio Francisco , Cano-Pumarega Irene , Sánchez-de-la-Torre Manuel , Ortigado Alfonso , López-Dueñas Ana , Fidalgo Laura , Rodríguez Ángel , Mediano Olga , Network Spanish Sleep
Published: November 2022

Current data support an increase in the prevalence of high blood pressure (HBP) in pediatric patients with sleep-disordered breathing (SDB). Adeno-tonsillectomy has been shown to be an effective treatment for most patients. Our objective was to determine the prevalence of HBP in pediatric patients with SDB and the impact of adeno-tonsillectomy with a multicenter, longitudinal, and prospective study that included 286 children referred for suspected SDB. The diagnosis of SDB was established by polysomnography (PSG) and the diagnosis of HBP by 24-h ambulatory blood pressure monitoring (ABPM). In patients without SDB and SDB without treatment indication, these tests were repeated six months after the baseline visit. For patients with medical treatment for SDB, the tests were repeated six months after the treatment initiation. Finally, in patients with surgery indication, ABPM was performed just before surgical treatment and ABPM and PSG six months after the intervention. The study contributes to elucidating the association between SDB and HBP in pediatric patients. Moreover, it contributes to determining if intervention with adeno-tonsillectomy is associated with BP reduction. The results have direct implications for the management of SDB, providing essential information on treatment indications for existing clinical guidelines. NCT03696654.
Analysis of Therapeutic Decisions for Infantile Hemangiomas: A Prospective Study Comparing the Hemangioma Severity Scale with the Infantile Hemangioma Referral Score
Authors: Qiu Tong , Yang Kaiying , Dai Shiyi , Chen Siyuan , Ji Yi
Published: November 2022

Background: In view of the high incidence of infantile hemangioma (IH) in infants and young children, a comprehensive and reasonable evaluation scale for referral is urgently needed. This study compared the influence of the Hemangioma Severity Scale (HSS) and the Infantile Hemangioma Referral Score (IHReS) on treatment decisions for infantile hemangioma patients. Objective: We aimed to establish a reliable and effective evaluation method for referral. Methods: This was a prospective study to determine whether treatment was needed for IH patients after evaluation with the HSS and IHReS. Results: A total of 266 consecutive referred IH patients were evaluated for the risk of IH, and the treatment rate was 80.8%. The area under the curve (AUC) of the subject receiver operating characteristic curve (ROC) of treatment decision making after referral by the HSS was 0.703 (95% CI: 0.634–0.772), and after referral by the IHReS was 0.892 (95% CI: 0.824–0.960). Limitations: This was a single-center study. Conclusions: For decisions regarding the treatment of IH patients, the IHReS has a higher efficiency and sensitivity than the HSS. However, the specificity of the IHReS is lower than that of the HSS.
A Systematic Review of the Diagnosis and Treatment of Non-Typhoid Salmonella Spondylodiscitis in Immunocompetent Children
Authors: Katzouraki Galateia , Vasiliadis Elias S. , Marougklianis Vasileios , Evangelopoulos Dimitrios Stergios , Pneumaticos Spyros G.
Published: November 2022

The aim of this systematic review is to distinguish the clinical features of immunocompetent children with non-typhoid Salmonella spondylodiscitis and summarize the diagnosis, diagnostic tools, and treatment methods to guide clinicians. The review was conducted according to the preferred PRISMA guidelines. We conducted a literature search in the PubMed, Embase, and Cochrane Library databases. Article screening, data extraction, and study evaluation were performed by two independent reviewers. A total of 20 articles, published between 1977 and 2020, were selected, which included 21 patients with average age of 12.76 years (range, 2–18) without comorbidities; in total, 19% of the patients had positive blood cultures for non-typhoid Salmonella, and 80.9% underwent either CT-guided or open biopsy, which were positive for NTS. All infections were monomicrobial, and 11 different serotypes of non-typhoid Salmonella were identified. Analyzing the reviewed cases, 52.4% of the patients presented with fever, 90.5% had localized pain, and only 19% had gastroenteritis. The most common level of discitis was the lumbar region, especially the L4/L5 level. Primarily, third-generation cephalosporin was administered, and antibiotic treatment was given for an average of 9.6 weeks. Non-typhoid Salmonella spondylodiscitis is a rare clinical entity in healthy and immunocompetent children. The identification of the responsible organism is essential to guide antibiotic therapy and define the treatment duration. A significant limiting factor in this systematic review was the lack of published research articles and case series due to the rarity of the disease.