bluuebunny/crossref_metadata_2025 huggingface dataset:
Network Association of Biochemical and Inflammatory Abnormalities With Psychiatric Symptoms in First-Episode Schizophrenia Patients
Authors: Yan Junwei , Chen Yuanyuan , Ju Peijun , Gao Jianliang , Zhang Loufeng , Li Jingwei , Wang Keming , Zhang Jie , Li Chao , Xia Qingrong , Zhu Cuizhen , Zhang Xulai
Published: February 2022

Background

Cardiovascular disease (CVD) risk factors such as dyslipidemia and systemic aberrant inflammatory processes may occur in patients with psychotic disorders, which may cause increased mortality. The interplay between immune and metabolic markers and its contribution to the clinical symptoms of schizophrenia (SCZ) remain unclear. This study aimed to examine the association of a series of inflammatory factors, plasma biochemical indicators, and SCZ clinical symptomatology with the severity of SCZ symptoms.

Methods

A total of 115 participants, including 79 first-episode drug-naïve patients with SCZ and 36 healthy controls, were enrolled in this study. Semi-structured interviews were used to collect sociodemographic data, family history of SCZ, and medical and psychiatric history. The Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS) were administered by a clinical psychiatrist to evaluate the symptom severity of patients with SCZ. Plasma inflammatory cytokines were measured by a fully automated electrochemiluminescent immunoassay (Meso Scale Discovery).

Results

Blood routine, biochemical, and inflammation cytokine test results showed that the levels of white blood cell count, neutrophil count, natrium, CRP, IL-8, IL-6, IL-13, and IL-16 significantly increased in the case group than in the healthy controls (p < 0.05), whereas levels of red blood cell count, hemoglobin concentration, mean corpuscular hemoglobin concentration, total protein, albumin, total bile acid, high-density lipoprotein (HDL), apolipoprotein A1, blood urea nitrogen, kalium and IL-15 were lower than in the healthy controls (p < 0.05). Correlation network analysis results shown that the natrium, HDL and red blood cell count were the top 3 factors closely to with BPRS and PANSS related clinical symptoms among of correlation network (degree = 4). ROC curve analysis explored the IL-16, IL-8, IL-13, IL-15, natrium, and HDL had highly sensitivity and specificity to the predictive validity and effectiveness for SCZ symptoms.

Conclusion

Our study revealed a complex interactive network correlation among the cardiovascular risk factors, biological immunity profiles, and psychotic symptoms in first-episode patients. Abnormal inflammatory factors and CVD risk factors had high sensitivity and specificity for predicting SCZ symptoms. Generally, our study provided novel information on the immune-related mechanisms involved in early CVD risk in patients with psychotic disorders.
The Lives of Native Hawaiian Elders and Their Experiences With Healthcare: A Qualitative Analysis
Authors: Kawakami Keilyn Leina‘ala , Muneoka Shelley , Burrage Rachel L. , Tanoue Leslie , Haitsuka Kilohana , Braun Kathryn L.
Published: February 2022

Native Hawaiians are proud and resilient people who have endured significant impacts from colonization. Despite being in a time of vibrant cultural revitalization, Native Hawaiians have a shorter life expectancy than other racial and ethnic groups in Hawai‘i. The primary aim of this paper was to share data from the first year of a 5-year study with Native Hawaiian kūpuna (elders) on their experiences with healthcare, along with barriers to accessing healthcare. Ten kūpuna living in rural areas of Hawai‘i participated in three interviews each, which were held in an informal, talk-story style. The first interview focused on establishing rapport. The second interview focused on the kūpuna's strengths, resiliencies, and what they would like to pass to the next generation. The third interview focused on the elders' experiences with healthcare, which is the focus of this paper. All ten kūpuna reported growing up with limited access to Western healthcare; rather, their families successfully treated many illnesses and injuries with lā‘au lapa‘au (Hawaiian herbal medicine) and other traditional healing practices, as they had done for generations. As Western medicine became more prevalent and accessible, they used both, but many preferred holistic treatments such as prayer, a return to the traditional diet, and lā‘au lapa‘au. As a group, the kūpuna rated their health as fair to good; two had diabetes, two had cardiovascular disease, four had neuropathies, and five were cancer survivors. The kūpuna reported high turnover among providers in rural communities. Limited access to specialists often required them to travel to Honolulu for care, which was costly and especially difficult during coronavirus disease 2019 (COVID-19). Regardless of provider ethnicity, the kūpuna appreciated those who took the time to get to know them as people and respected Hawaiian cultural practices. They advised that Western providers speak honestly and directly, have compassion, and build connections to patients and their communities.
Feasibility and Acceptability of Game-Based Cortical Priming and Functional Lower Limb Training in a Remotely Supervised Home Setting for Chronic Stroke: A Case Series
Authors: Lim Hyosok , Marjanovic Nicholas , Luciano Cristian , Madhavan Sangeetha
Published: February 2022

Background

Movement-based priming has been increasingly investigated to accelerate the effects of subsequent motor training. The feasibility and acceptability of this approach at home has not been studied. We developed a game-based priming system (DIG-I-PRIMETM) that engages the user in repeated ankle movements using serious games. We aimed to determine the feasibility, acceptability, and preliminary motor benefits of an 8-week remotely supervised telerehabilitation program utilizing game-based movement priming combined with functional lower limb motor training in chronic stroke survivors.

Methods

Three individuals with stroke participated in a telerehabilitation program consisting of 20-min movement-based priming using the DIG-I-PRIMETM system followed by 30-min of lower limb motor training focusing on strength and balance. We evaluated feasibility using reported adverse events and compliance, and acceptability by assessing participant perception of the game-based training. Motor gains were assessed using the 10-m walk test and Functional Gait Assessment.

Results

All participants completed 24 remotely supervised training sessions without any adverse events. Participants reported high acceptability of the DIG-I-PRIMETM system, reflected by high scores on satisfaction, enjoyment, user-friendliness, and challenge aspects of the system. Participants reported overall satisfaction with our program. Post-training changes in the 10-m walk test (0.10–0.31 m/s) and Functional Gait Assessment (4–7 points) exceeded the minimal clinically important difference.

Conclusion

Our results indicate that a remotely supervised game-based priming and functional lower limb exercise program is feasible and acceptable for stroke survivors to perform at home. Also, improved walking provides preliminary evidence of game-based priming to be beneficial as a telerehabilitation strategy for stroke motor recovery.
Survey of Ethnoveterinary Medicines Used to Treat Livestock Diseases in Omusati and Kunene Regions of Namibia
Authors: Eiki Ndahambelela , Maake Matome , Lebelo Sogolo , Sakong Bellonah , Sebola Nthabiseng , Mabelebele Monnye
Published: February 2022

The aim of this study was to find, evaluate, and document ethnoveterinary medications used to treat livestock ailments in Namibia's Omusati and Kunene regions. A semi-structured questionnaire was used to interview a total of 100 people. The results of the survey will be useful in creating the groundwork for future scientific research and validation. There were 15 veterinary medicinal plant species identified, which were divided into 10 families. The only types of growth that were utilized were trees, herbs, and bushes. Leaves (71%) were the most widely used plant parts for ethnoveterinary medicine (EVM), followed by bark (14%), stem (8%), and root (7%). Fresh components were frequently preferred in medical compositions. Oral administration was the most common (42.76%), followed by cutaneous (topical) administration (36.18%). Indigenous knowledge was largely passed down through the generations by word of mouth, indicating that it was vulnerable to fragmentation and loss. EVMs were crushed, soaked in water, and administered orally or topically. Farmers who were older had greater EVM knowledge than those who were younger. Ziziphus mucronate, Combretum collinum, and Colophospermum mopane were used in the treatment of diarrhea. Z. mucronate was also used in the treatment of mastitis. Skin infections were treated using Aloe esculenta and Salvadora persica. Ximenia americana and C. imberbe were used to treat eye infections in cattle, goats, and sheep. Retained placentas were treated using Acacia nilotica, A. erioloba, and Grewia flavescens. Roots from Fockea angustifolia were used in treating anthrax. A. esculenta Leach placed best with a fidelity level (FL) value of 90%, followed by A. littoralis Baker in second place (56%), and Combretum collinum Fresen in third place (54%). The majority of EVM recipes took 2–3 days to recover. More research is needed to determine the minimum inhibitory concentrations, biological activities, and toxicities, as well as characterize the chemical components of the plants and determine whether there is a plausible mechanism by which plant chemicals or possible physiological effects could achieve the results described by the respondents.
Symmetrical Dimethylarginine as a Diagnostic Parameter in Hermann's Tortoises (Testudo hermanni)
Authors: Lehmann Verena , Altherr Barblin , Pantchev Nikola , Öfner Sabine , Zablotski Yury , Murphy Rachel , Coyne Michael , Kölle Petra
Published: February 2022

Background

Despite improvements in habitational conditions, kidney disease is relatively common in tortoises.

Objectives

Purpose of this study was the establishment of Symmetrical dimethylarginine (SDMA) reference values for clinically healthy Hermann's Tortoises.

Animals

Clinically healthy Hermann's Tortoises (n = 131) were included in the period from October 2017 to September 2019.

Methods

Creatinine and other biomarkers were tested at IDEXX Laboratories, Germany using residual blood samples from Hermann's tortoises. SDMA was measured with the IDEXX test and verified by liquid chromatography-mass spectrometry at IDEXX Laboratories, USA.

Results

SDMA values ranged from 1 to 21 μg/dl (n = 131) for the IDEXX SDMA Test and SDMA values ranged from 1 to 17 μg/dl (n = 82) for LC-MS. For the comparison of the two measuring systems, the following results were obtained R2 = 0.75 (p < 0.001).

Conclusion and Clinical Importance

SDMA can be measured in Hermann's Tortoises and the reference values range in clinically healthy animals is comparable to that of dogs and cats.
A Review of Deep Learning Algorithms and Their Applications in Healthcare
Authors: Abdel-Jaber Hussein , Devassy Disha , Al Salam Azhar , Hidaytallah Lamya , EL-Amir Malak
Published: February 2022

Deep learning uses artificial neural networks to recognize patterns and learn from them to make decisions. Deep learning is a type of machine learning that uses artificial neural networks to mimic the human brain. It uses machine learning methods such as supervised, semi-supervised, or unsupervised learning strategies to learn automatically in deep architectures and has gained much popularity due to its superior ability to learn from huge amounts of data. It was found that deep learning approaches can be used for big data analysis successfully. Applications include virtual assistants such as Alexa and Siri, facial recognition, personalization, natural language processing, autonomous cars, automatic handwriting generation, news aggregation, the colorization of black and white images, the addition of sound to silent films, pixel restoration, and deep dreaming. As a review, this paper aims to categorically cover several widely used deep learning algorithms along with their architectures and their practical applications: backpropagation, autoencoders, variational autoencoders, restricted Boltzmann machines, deep belief networks, convolutional neural networks, recurrent neural networks, generative adversarial networks, capsnets, transformer, embeddings from language models, bidirectional encoder representations from transformers, and attention in natural language processing. In addition, challenges of deep learning are also presented in this paper, such as AutoML-Zero, neural architecture search, evolutionary deep learning, and others. The pros and cons of these algorithms and their applications in healthcare are explored, alongside the future direction of this domain. This paper presents a review and a checkpoint to systemize the popular algorithms and to encourage further innovation regarding their applications. For new researchers in the field of deep learning, this review can help them to obtain many details about the advantages, disadvantages, applications, and working mechanisms of a number of deep learning algorithms. In addition, we introduce detailed information on how to apply several deep learning algorithms in healthcare, such as in relation to the COVID-19 pandemic. By presenting many challenges of deep learning in one section, we hope to increase awareness of these challenges, and how they can be dealt with. This could also motivate researchers to find solutions for these challenges.
Effects of COVID-19 Pandemic on Agricultural Food Production among Smallholder Farmers in Northern Drakensberg Areas of Bergville, South Africa
Authors: Mthembu Bonginkosi E. , Mkhize Xolile , Arthur Georgina D.
Published: February 2022

COVID-19 pandemic has greatly affected social and economic activities in the agriculture systems. The extent of pandemic disruptions on agriculture food production systems is lamentably scanty in rural areas. A survey was carried out in the Northern Drakensberg areas of Bergville, and it assessed the impact of COVID-19 on agricultural food production in smallholder farming systems comprising crop-livestock systems. A survey was conducted using structured questionnaires that measured the impact of COVID-19 within farming operations and average crop yield trends pre-COVID-19 and during COVID-19. Most farmers (77.1 to 92.4%) reported having limitations in accessing agricultural inputs of seeds, fertilizers, herbicides, fungicides, and insecticides during the COVID-19 pandemic. Results indicated a continuous decrease in yields of maize, dry beans, and soybeans across two years of cropping seasons during the COVID-19 pandemic. The study demonstrated that COVID-19 lockdowns accompanied by movement restrictions negatively impacted food production of staple crops (maize, dry beans, soybeans) despite suitable rains received during COVID-19 production periods. COVID-19 policies and legislations sensitive to the plight of poor rural communities are necessary as these communities are more reliant on local agricultural food production for their livelihoods and income. Strong co-operations must be established among input suppliers, smallholder farmers associations, extension services, and local retailers to assist smallholders to obtain inputs at local retailers even during COVID-19 lockdown restrictions.
Electrical Equalization Analysis of PAM-4 Transmission in Short-Reach Optical Systems
Authors: Arie Dana , Katz Gilad
Published: February 2022

Inclusive and intensive performance analysis of electrical equalizers in a short-reach optical system using four-level pulse amplitude modulation (PAM-4) is presented in this paper. Two equalizers are used—a feedforward equalizer and decision feedback equalizer using the least mean square algorithm. The sensitivity to cut-off frequency for the transmitter and receiver filters, fiber length and number of equalizers taps in the means of the bit error rate vs. optical input power are shown. The analysis reveals the considerable impact of the filters’ bandwidth, particularly in the receiver, on the equalizer performance. These results and their reasons are analyzed and broadly discussed.
Observed Climatology and Trend in Relative Humidity, CAPE, and CIN over India
Authors: Khan Pathan Imran , Ratnam Devanaboyina Venkata , Prasad Perumal , Basha Ghouse , Jiang Jonathan H. , Shaik Rehana , Ratnam Madineni Venkat , Kishore Pangaluru
Published: February 2022

Water vapor is the most dominant greenhouse gas in the atmosphere and plays a critical role in Earth’s energy budget and hydrological cycle. This study aims to characterize the long-term seasonal variation of relative humidity (RH), convective available potential energy (CAPE), and convective inhibition (CIN) from surface and radiosonde observations from 1980–2020. The results show that during the monsoon season, very high RH values are depicted while low values are depicted during the pre-monsoon season. West Coast stations represent large RH values compared to other stations throughout the year. Irrespective of the season, the coastal regions show higher RH values during monsoon season. Regardless of season, the coastal regions have higher RH values during the monsoon season. During the pre-monsoon season, the coastal region has high RH values, whereas other regions have high RH values during the monsoon season. The rate of increase in RH in North-West India is 5.4%, followed by the West Coast, Central, and Southern parts of India. An increase in water vapor leads to raised temperature, which alters the instability conditions. In terms of seasonal variation, our findings show that CAPE follows a similar RH pattern. CAPE increases sharply in Central India and the West Coast region, while it declines in South India. Opposite features are observed in CIN with respect to CAPE variability over India. The results of the study provide additional evidence with respect to the role of RH as an influencing factor for an increase in CAPE over India.
Vec2Dynamics: A Temporal Word Embedding Approach to Exploring the Dynamics of Scientific Keywords—Machine Learning as a Case Study
Authors: Dridi Amna , Gaber Mohamed Medhat , Azad Raja Muhammad Atif , Bhogal Jagdev
Published: February 2022

The study of the dynamics or the progress of science has been widely explored with descriptive and statistical analyses. Also this study has attracted several computational approaches that are labelled together as the Computational History of Science, especially with the rise of data science and the development of increasingly powerful computers. Among these approaches, some works have studied dynamism in scientific literature by employing text analysis techniques that rely on topic models to study the dynamics of research topics. Unlike topic models that do not delve deeper into the content of scientific publications, for the first time, this paper uses temporal word embeddings to automatically track the dynamics of scientific keywords over time. To this end, we propose Vec2Dynamics, a neural-based computational history approach that reports stability of k-nearest neighbors of scientific keywords over time; the stability indicates whether the keywords are taking new neighborhood due to evolution of scientific literature. To evaluate how Vec2Dynamics models such relationships in the domain of Machine Learning (ML), we constructed scientific corpora from the papers published in the Neural Information Processing Systems (NIPS; actually abbreviated NeurIPS) conference between 1987 and 2016. The descriptive analysis that we performed in this paper verify the efficacy of our proposed approach. In fact, we found a generally strong consistency between the obtained results and the Machine Learning timeline.
Low-Cost Algorithms for Metabolic Pathway Pairwise Comparison
Authors: Arias-Méndez Esteban , Barquero-Morera Diego , Torres-Rojas Francisco J.
Published: February 2022

Metabolic pathways provide key information for achieving a better understanding of life and all its processes; this is useful information for the improvement of medicine, agronomy, pharmacy, and other similar areas. The main analysis tool used to study these pathways is based on pathway comparison, using graph data structures. Metabolic pathway comparison has been defined as a computationally complex task. In a previous work, two new algorithms were introduced to treat the problem of metabolic pathway pairwise comparison. Here we provide an extended analysis with more data and a deeper analysis of metabolic pathway comparison as listed in the discussion and results section.
Decision-Making Tool for the Selection of Priority Areas for Building Rehabilitation in Barcelona
Authors: Cornadó Còssima , Vima-Grau Sara , Garcia-Almirall Pilar , Uzqueda Angel , de la Asunción Mireia
Published: February 2022

The promotion of rehabilitation is an urgent necessity in today’s consolidated cities, both due to the need to update their buildings to achieve habitability and safety standards that are required nowadays, as well as to stop the deterioration of buildings in vulnerable environments, where paradoxically the obtainment of economic resources to invest in building maintenance and upgrade is scarcer. Decision making on the delimitation of areas in which the need to invest is higher is extremely complex and often relies on large secondary data studies that are contrasted with local stakeholders’ intuition and knowledge on the ground. Usually, rehabilitation aids are directed to relatively large areas, where a certain need may be found. However, these areas are often excessively wide and specific needs that would require special focus can be diluted in the whole. The current trend of area-based and site-specific rehabilitation programs calls for precise and focused data studies and methodologies. The research presented here provides a methodology for the selection of priority areas to promote rehabilitation in the context of Barcelona’s vulnerable neighborhoods. The selection methodology combines primary and secondary data with a very high level of disaggregation that identifies where the needs are greatest, and it also provides a tool that is still based on primary disaggregated data for the delimitation of areas. The results obtained highlight specific priority areas such as parts of the Raval, Carmel and Besòs-Maresme neighborhoods within larger zones that had been previously defined as vulnerable. The proposed methodology seeks to provide tools to foster evidence-based decision making, thus improving both the understanding of reality and its spatial distribution through data mining techniques and data visualization.
A Global Evaluation of the Performance Indicators of Colorectal Cancer Screening with Fecal Immunochemical Tests and Colonoscopy: A Systematic Review and Meta-Analysis
Authors: Ding Hanyue , Lin Jiaye , Xu Zijun , Chen Xiao , Wang Harry H. X. , Huang Liwen , Huang Junjie , Zheng Zhijie , Wong Martin C. S.
Published: February 2022

(1) Background: To summarize the achievements of the performance indicators of colorectal cancer (CRC) screening programs that used the fecal immunochemical test (FIT) as a primary screening modality and colonoscopy as a subsequent confirmatory test. (2) Methods: PubMed, Ovid MEDLINE, Embase, and Cochrane were searched from inception to September 2020. We included original articles published in English, and performed hand searching for relevant national reports. We generated pooled achievement estimates of the performance indicators by “metaprop” (R software 3.6.3). Meta-regression analyses and subgroup analyses were also conducted. (3) Results: We included 93 studies involving nearly 90 million people-times. The participation rate ranged from 6.80% to 95.98%, which was associated with study type, continents, FIT number, age, and round. The pooled FIT invalid rate and positivity rate were 1.08% and 7.28%, respectively. The pooled estimates of FIT detection were 2.26% for adenoma, 1.26% for advanced adenoma, and 0.28% for CRC. In addition, only seven studies reported that their colonoscopy compliance rate reached 90% among 69 studies. The colonoscopy completion rate (21/40 studies > 95%) and the complication rate (18/27 studies < 0.5%) were acceptable. (4) Conclusions: Our findings could help to identify the areas that could be improved and finally optimize the CRC screening programs.
Lymphatic Function of the Lower Limb after Groin Dissection for Vulvar Cancer and Reconstruction with Lymphatic SCIP Flap
Authors: Caretto Anna Amelia , Stefanizzi Gianluigi , Fragomeni Simona Maria , Federico Alex , Tagliaferri Luca , Lancellotta Valentina , Scambia Giovanni , Gentileschi Stefano
Published: February 2022

Inguinofemoral lymphadenectomy, frequently performed for vulvar cancer, is burdened with substantial immediate and long-term morbidity. One of the most disabling treatment-related sequelae is lower limb lymphedema (LLL). The present study aims to describe the wound complications and the severity of LLL in patients who have undergone groin dissection for vulvar cancer and immediate inguinal reconstruction with the Lymphatic Superficial Circumflex Iliac Perforator flap (L-SCIP). We retrospectively reviewed the data of patients who underwent bilateral groin dissection and unilateral inguinal reconstruction with the L-SCIP. The presence and severity of postoperative LLL during the follow-up period were assessed by lymphoscintigraphy and limbs’ volume measurement. In addition, immediate complications at the level of the inguinal area were registered. The changes between preoperative and postoperative limb volumes were analyzed by Student’s t test. p values < 0.05 were considered significant. Thirty-one patients were included. The mean variation of volume was 479 ± 330 cc3 in the side where groin reconstruction had been performed, and 683 ± 425 cc3 in the contralateral side, showing smaller variation in the treated side (p = 0.022). Lymphoscintigraphy confirmed the clinical findings. Based on our results, inguinal reconstruction with L-SCIP performed at the same time of groin dissection in patients treated for vulvar cancer can provide a significant protective effect on LLL.
Alpha-Emitter Radiopharmaceuticals and External Beam Radiotherapy: A Radiobiological Model for the Combined Treatment
Authors: Sarnelli Anna , Belli Maria Luisa , Azzali Irene , Loi Emiliano , Severi Stefano , Strigari Lidia
Published: February 2022

Previously published studies combined external beam radiotherapy (EBRT) treatments with different activities of 223Ra. The data of two-year overall survival (2y-OS) and neutropenia (TOX) incidence when combining EBRT and 223Ra are not homogeneous in literature. We adapted the linear–quadratic model (LQ) to 223Ra therapy using brachytherapy formalism for a mixture of radionuclides, considering the contribution of all daughter isotopes in the decay chain. A virtual cohort of patients undergoing 223Ra therapy was derived using data from the literature. The doses delivered using 223Ra and EBRT were converted into biologically equivalent doses. Fixed-effect logistic regression models were derived for both the 2y-OS and TOX and compared with available literature. Based on the literature search, four studies were identified to have reported the 223Ra injection activity levels varying from the placebo (0) to 80 kBq/kg, associated or not with EBRT. Logistic regression models revealed a dose-dependent increase in both the 2y-OS (intercept = −1.364; slope = 0.006; p-value ≤ 0.05) and TOX (−5.035; 0.018; ≤0.05) using the EBRT schedule of 8 Gy in 1 fr. Similar results were obtained for other schedules. Discrepancies between our TOX model and those derived for EBRT combined with chemotherapy are discussed. Radiobiological models allow us to estimate dose-dependent relationships, to predict the OS and TOX following combined 223Ra + EBRT treatment, which will guide future treatment optimization.
Knowns and Unknowns about CAR-T Cell Dysfunction
Authors: Titov Aleksei , Kaminskiy Yaroslav , Ganeeva Irina , Zmievskaya Ekaterina , Valiullina Aygul , Rakhmatullina Aygul , Petukhov Alexey , Miftakhova Regina , Rizvanov Albert , Bulatov Emil
Published: February 2022

Immunotherapy using chimeric antigen receptor (CAR) T cells is a promising option for cancer treatment. However, T cells and CAR-T cells frequently become dysfunctional in cancer, where numerous evasion mechanisms impair antitumor immunity. Cancer frequently exploits intrinsic T cell dysfunction mechanisms that evolved for the purpose of defending against autoimmunity. T cell exhaustion is the most studied type of T cell dysfunction. It is characterized by impaired proliferation and cytokine secretion and is often misdefined solely by the expression of the inhibitory receptors. Another type of dysfunction is T cell senescence, which occurs when T cells permanently arrest their cell cycle and proliferation while retaining cytotoxic capability. The first section of this review provides a broad overview of T cell dysfunctional states, including exhaustion and senescence; the second section is focused on the impact of T cell dysfunction on the CAR-T therapeutic potential. Finally, we discuss the recent efforts to mitigate CAR-T cell exhaustion, with an emphasis on epigenetic and transcriptional modulation.
External Validation of a Radiomics Model for the Prediction of Complete Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer
Authors: Bordron Anaïs , Rio Emmanuel , Badic Bogdan , Miranda Omar , Pradier Olivier , Hatt Mathieu , Visvikis Dimitris , Lucia François , Schick Ulrike , Bourbonne Vincent
Published: February 2022

Objective: Our objective was to develop a radiomics model based on magnetic resonance imaging (MRI) and contrast-enhanced computed tomography (CE-CT) to predict pathological complete response (pCR) to neoadjuvant treatment in locally advanced rectal cancer (LARC). Material: All patients treated for a LARC with neoadjuvant CRT and subsequent surgery in two separate institutions between 2012 and 2019 were considered. Both pre-CRT pelvic MRI and CE-CT were mandatory for inclusion. The tumor was manually segmented on the T2-weighted and diffusion axial MRI sequences and on CE-CT. In total, 88 radiomic parameters were extracted from each sequence using the Miras© software, with a total of 822 features by patient. The cohort was split into training (Institution 1) and testing (Institution 2) sets. The ComBat and Synthetic Minority Over-sampling Technique (SMOTE) approaches were used to account for inter-institution heterogeneity and imbalanced data, respectively. We selected the most predictive characteristics using Spearman’s rank correlation and the Area Under the ROC Curve (AUC). Five pCR prediction models (clinical, radiomics before and after ComBat, and combined before and after ComBat) were then developed on the training set with a neural network approach and a bootstrap internal validation (n = 1000 replications). A cut-off maximizing the model’s performance was defined on the training set. Each model was then evaluated on the testing set using sensitivity, specificity, balanced accuracy (Bacc) with the predefined cut-off. Results: Out of the 124 included patients, 14 had pCR (11.3%). After ComBat harmonization, the radiomic and the combined models obtained a Bacc of 68.2% and 85.5%, respectively, while the clinical model and the pre-ComBat combined achieved respective Baccs of 60.0% and 75.5%. Conclusions: After correction of inter-site variability and imbalanced data, addition of radiomic features enhances the prediction of pCR after neoadjuvant CRT in LARC.
NOTCH1 Intracellular Domain and the Tumor Microenvironment as Prognostic Markers in HNSCC
Authors: Schmidl Benedikt , Siegl Michael , Boxberg Melanie , Stögbauer Fabian , Jira Daniel , Winter Christof , Stark Leonhard , Pickhard Anja , Wollenberg Barbara , Wirth Markus
Published: February 2022

(1) Background: NOTCH1 is the second most common mutated gene in whole-exome sequencing of HNSCC. The aim of this project was to gain further insight into the relevance of NOTCH1 in HNSCC, potentially establishing NOTCH1 as a prognostic marker or therapeutic target; (2) Methods: NOTCH1 was silenced via RNA interference in six HNSCC cell lines and the impact was evaluated in migration and proliferation assays. Subsequently, the protein expression of NOTCH1 intracellular domain (NICD) and NOTCH1 mRNA expression were examined in 70 oropharyngeal squamous cell cancer tissue samples. Lastly, the NICD expression was compared with the local infiltration of lymphocytes, measured with the immunoscore; (3) Results: Knockdown of NOTCH1 decreased migration and proliferation. A high NICD expression was associated with lower OS. A high immunoscore resulted in significantly better OS. NICD expression was independent of the immunoscore and as a whole differentiated three distinct prognostic groups; (4) Conclusions: These data suggest that NOTCH1 is involved in migration and proliferation of HNSCC cell lines. In vivo, NICD expression was associated with overall survival and could, therefore, be used as a prognostic marker. NICD expression differs from NOTCH1 mRNA levels, potentially explaining the previously suggested bimodal role as an oncogene and tumor suppressor in HNSCC.
Survival Analysis in Endometrial Carcinomas by Type of Surgical Approach: A Matched-Pair Study
Authors: Coronado Pluvio J. , Rychlik Agnieszka , Baquedano Laura , García-Pineda Virginia , Martínez-Maestre Maria A. , Querleu Denis , Zapardiel Ignacio
Published: February 2022

(1) Background: This study aimed to analyze the impact of surgical approach on survival rates in women diagnosed with endometrial cancer. (2) Methods: A retrospective multicenter cohort of 1382 women diagnosed with EC was performed. A total of 684 (49.5%) women underwent minimally invasive surgery, 233 (34%) underwent robotic-assisted laparoscopy (RAL), 451 (66%) underwent conventional laparoscopy (LPS), and 698 (50.5%) underwent open surgery (OP). Sociodemographic features, tumor characteristics, and survival rates were analyzed in the whole sample and in a matched-pair model. (3) Results: Women operated on by OP were significantly older, presented more comorbidities, and had more aggressive tumors. Disease-free (DFS), overall (OS), and specific survival related to EC (SS) amounts were significantly higher for MIS compared to OP (p < 0.001). When matched by age, body mass index, comorbidities, ASA score, histological type, grade, myometrial invasion, and FIGO stage, 798 patients were selected. DFS, OS, and SS amounts were similar between the MIS and OP groups. (4) Conclusions: The surgical approach for women with EC does not impact DFS or OS amounts when matched by homogeneous groups.
Line-Field Confocal Optical Coherence Tomography Increases the Diagnostic Accuracy and Confidence for Basal Cell Carcinoma in Equivocal Lesions: A Prospective Study
Authors: Gust Charlotte , Schuh Sandra , Welzel Julia , Daxenberger Fabia , Hartmann Daniela , French Lars E. , Ruini Cristel , Sattler Elke C.
Published: February 2022

Diagnosing clinically unclear basal cell carcinomas (BCCs) can be challenging. Line-field confocal optical coherence tomography (LC-OCT) is able to display morphological features of BCC subtypes with good histological correlation. The aim of this study was to investigate the accuracy of LC-OCT in diagnosing clinically unsure cases of BCC compared to dermoscopy alone and in distinguishing between superficial BCCs and other BCC subtypes. Moreover, we addressed pitfalls in false positive cases. We prospectively enrolled 182 lesions of 154 patients, referred to our department to confirm or to rule out the diagnosis of BCC. Dermoscopy and LC-OCT images were evaluated by two experts independently. Image quality, LC-OCT patterns and criteria, diagnosis, BCC subtype, and diagnostic confidence were assessed. Sensitivity and specificity of additional LC-OCT were compared to dermoscopy alone for identifying BCC in clinically unclear lesions. In addition, key LC-OCT features to distinguish between BCCs and non-BCCs and to differentiate superficial BCCs from other BCC subtypes were determined by linear regressions. Diagnostic confidence was rated as “high” in only 48% of the lesions with dermoscopy alone compared to 70% with LC-OCT. LC-OCT showed a high sensitivity (98%) and specificity (80%) compared to histology, and these were even higher (100% sensitivity and 97% specificity) in the subgroup of lesions with high diagnostic confidence. Interobserver agreement was nearly perfect (95%). The combination of dermoscopy and LC-OCT reached a sensitivity of 100% and specificity of 81.2% in all cases and increased to sensitivity of 100% and specificity of 94.9% in cases with a high diagnostic confidence. The performance of LC-OCT was influenced by the image quality but not by the anatomical location of the lesion. The most specific morphological LC-OCT criteria in BCCs compared to non-BCCs were: less defined dermoepidermal junction (DEJ), hyporeflective tumor lobules, and dark rim. The most relevant features of the subgroup of superficial BCCs (sBCCs) were: string of pearls pattern and absence of epidermal thinning. Our diagnostic confidence, sensitivity, and specificity in detecting BCCs in the context of clinically equivocal lesions significantly improved using LC-OCT in comparison to dermoscopy only. Operator training for image acquisition is fundamental to achieve the best results. Not only the differential diagnosis of BCC, but also BCC subtyping can be performed at bedside with LC-OCT.
The Roles of microRNAs in Cancer Multidrug Resistance
Authors: Pavlíková Lucia , Šereš Mário , Breier Albert , Sulová Zdena
Published: February 2022

Cancer chemotherapy may induce a multidrug resistance (MDR) phenotype. The development of MDR is based on various molecular causes, of which the following are very common: induction of ABC transporter expression; induction/activation of drug-metabolizing enzymes; alteration of the expression/function of apoptosis-related proteins; changes in cell cycle checkpoints; elevated DNA repair mechanisms. Although these mechanisms of MDR are well described, information on their molecular interaction in overall multidrug resistance is still lacking. MicroRNA (miRNA) expression and subsequent RNA interference are candidates that could be important players in the interplay of MDR mechanisms. The regulation of post-transcriptional processes in the proteosynthetic pathway is considered to be a major function of miRNAs. Due to their complementarity, they are able to bind to target mRNAs, which prevents the mRNAs from interacting effectively with the ribosome, and subsequent degradation of the mRNAs can occur. The aim of this paper is to provide an overview of the possible role of miRNAs in the molecular mechanisms that lead to MDR. The possibility of considering miRNAs as either specific effectors or interesting targets for cancer therapy is also analyzed.
Glioblastoma Microenvironment and Cellular Interactions
Authors: Crivii Carmen-Bianca , Boșca Adina Bianca , Melincovici Carmen Stanca , Constantin Anne-Marie , Mărginean Mariana , Dronca Eleonora , Suflețel Rada , Gonciar Diana , Bungărdean Maria , Șovrea Alina
Published: February 2022

The central nervous system (CNS) represents a complex network of different cells, such as neurons, glial cells, and blood vessels. In tumor pathology, glial cells result in the highest number of cancers, and glioblastoma (GB) is considered the most lethal tumor in this region. The development of GB leads to the infiltration of healthy tissue through the interaction between all the elements of the brain network. This results in a GB microenvironment, a complex peritumoral hallo composed of tumor cells and several non-tumor cells (e.g., nervous cells, stem cells, fibroblasts, vascular and immune cells), which might be the principal factor for the ineffective treatment due to the fact that the microenvironment modulates the biologic status of the tumor with the increase in its evasion capacity. Crosstalk between glioma cells and the brain microenvironment finally inhibits the beneficial action of molecular pathways, favoring the development and invasion of the tumor and its increasing resistance to treatment. A deeper understanding of cell–cell interactions in the tumor microenvironment (TME) and with the tumor cells could be the basis for a more efficient therapy.
Mental Health and Quality of Life among Patients with Cancer during the SARS-CoV-2 Pandemic: Results from the Longitudinal ONCOVID Survey Study
Authors: De Jaeghere Emiel A. , Kanervo Heini , Colman Roos , Schrauwen Wim , West Paulien , Vandemaele Nele , De Pauw Aglaja , Jacobs Celine , Hilderson Ingeborg , Saerens Michael , Sundahl Nora , Vandecasteele Katrien , Naert Eline , Lapeire Lore , Kruse Vibeke , Rottey Sylvie , Lemmens Gilbert , Denys Hannelore G.
Published: February 2022

Purpose: This longitudinal survey study aimed to investigate the self-reported outcome measures of COVID-19 peritraumatic distress, depression, anxiety, stress, quality of life (QOL), and their associated factors in a cohort of cancer patients treated at a tertiary care hospital during the SARS-CoV-2 pandemic. Methods: Surveys were administered at four time points between 1 April 2020 and 18 September 2020. The surveys included the CPDI, DASS-21, and WHOQOL-BREF questionnaires. Results: Survey response rates were high (61.0% to 79.1%). Among the 355 participants, 71.3% were female, and the median age was 62.2 years (IQR, 53.9 to 69.1). The majority (78.6%) were treated with palliative intention. An important proportion of the participants reported symptoms of COVID-19 peritraumatic distress (34.2% to 39.6%), depression (27.6% to 33.5%), anxiety (24.9% to 32.7%), and stress (11.4% to 15.7%) at any time point during the study period. We did not find clinically meaningful mental health and QOL differences during the study period, with remarkably little change in between the pandemic’s first and second wave. We found no consistent correlates of mental health or QOL scores, including cancer type, therapy intention, and sociodemographic information. Conclusion: This cohort of cancer patients showed considerable resilience against mental health and QOL deterioration during the SARS-CoV-2 pandemic.
c-Met and EPHA7 Receptor Tyrosine Kinases Are Related to Prognosis in Clear Cell Renal Cell Carcinoma: Focusing on the Association with Myoferlin Expression
Authors: Jung Minsun , Lee Seokhyeon , Moon Kyung
Published: February 2022

Receptor tyrosine kinases (RTKs) are important targets for clear cell renal cell carcinoma (ccRCC) treatment. Myoferlin is a strong regulator of RTKs. To identify myoferlin-associated RTKs and their prognostic implications in ccRCC, we investigated the expression of RTKs and myoferlin using proteome-based evaluation and immunohistochemical staining in tissue microarray. Multivariate Cox analysis adjusted for TNM stage and WHO grade was performed (n = 410 and 506). Proteomic analysis suggested c-Met and EPHA7 as novel candidates for myoferlin-associated RTKs. We immunohistochemically validated the positive association between c-Met and myoferlin expression. High c-Met expression was independently associated with overall (hazard ratio (HR) = 1.153–2.919) and cancer-specific survival (HR = 1.150–3.389). The prognostic effect of high c-Met expression was also determined in an independent cohort (overall survival, HR = 1.503–3.771). Although expression of EPHA7 and myoferlin was not correlated, EPHA7 expression was independently associated with progression-free (HR = 1.237–4.319) and cancer-specific survival (HR = 1.214–4.558). In addition, network-based prioritization showed co-functional enrichment of c-Met and myoferlin, suggesting a novel regulatory function of myoferlin in c-Met signaling. This study indicates that c-Met and EPHA7 might be useful prognostic biomarkers, and the presumed myoferlin/c-Met pathway could be a novel therapeutic target in ccRCC.
Hg0 Removal by V2O5 Modified Palygorskite in Simulated Flue Gas at Low Temperature
Authors: Wang Junwei , Wang Huan , Jiang Caihong , Wang Xie , Zhang Jianli
Published: February 2022

The V2O5-modified palygorskite (V2O5/PG catalysts) were prepared and used for Hg0 removal in simulated flue gas at low temperature. It was found that the V2O5/PG catalyst had excellent performance for Hg0 removal at 150 °C. O2 exhibited a positive effect on Hg0 removal over V2O5/PG, while SO2 and H2O showed an inhibiting effect. However, Hg0 removal efficiency showed a promotion trend in the presence of H2O, SO2, and O2. The Brunauer–Emmett–Teller (BET) method, scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) were applied to characterize the physicochemical properties of the V2O5/PG catalyst. Mercury temperature-programmed desorption (Hg-TPD) experiments were also conducted to identify the mercury species adsorbed on the V2O5/PG catalyst, and the pathway of Hg0 removal over V2O5/PG was also discussed. The used V2O5/PG catalyst after Hg0 removal was regenerated, and its capability for Hg0 removal can be completely recovered. The V2O5/PG-Re-300 °C catalyst showed excellent performance and good stability for Hg0 removal after regeneration.
Calorific Characteristics of Larch (Larix decidua) and Oak (Quercus robur) Pellets Realized from Native and Torrefied Sawdust
Authors: Lunguleasa Aurel , Spirchez Cosmin , Olarescu Alin M.
Published: February 2022

This research aimed to evaluate the calorific characteristics of two biomasses from larch and oak sawdust in the form of native or torrefied pellets. Some calorific features of these two kinds of biomasses, such as ash content, higher and lower calorific values, calorific density and many others were highlighted, allowing for a comparison between oak and larch torrefied/not torrefied pellets. Installations and methods used for the process of torrefaction and for highlighting some of the calorific features were also evaluated. As a result of experiments, it was demonstrated that the larch and oak pellets were different in terms of density, but that after thermal treatment, the calorific values of both increased considerably. The investigations evidenced some increases in calorific value, up to 15.8%, for both the larch and oak sawdust/pellets. One of the main conclusions of this research was that, even though the role of biomass has diminished considerably in the last few decades, its role as a sustainable fuel remains relevant. Its use will become more widespread when the world’s population understands that fossil fuels are depletable and that they must be replaced by renewable fuels such as biomass.
Flow Scheduling in Data Center Networks with Time and Energy Constraints: A Software-Defined Network Approach
Authors: Fraga Martin , Micheletto Matías , Llinás Andrés , Santos Rodrigo , Zabala Paula
Published: February 2022

Flow scheduling in Data Center Networks (DCN) is a hot topic as cloud computing and virtualization are becoming the dominant paradigm in the increasing demand of digital services. Within the cost of the DCN, the energy demands associated with the network infrastructure represent an important portion. When flows have temporal restrictions, the scheduling with path selection to reduce the number of active switching devices is a NP-hard problem as proven in the literature. In this paper, an heuristic approach to schedule real-time flows in data-centers is proposed, optimizing the temporal requirements while reducing the energy consumption in the network infrastructure via a proper selection of the paths. The experiments show good performance of the solutions found in relation to exact solution approximations based on an integer linear programming model. The possibility of programming the network switches allows the dynamic schedule of paths of flows under the software-defined network management.