bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital Health Services through Patient Empowerment: Classification, Current State and Preliminary Impact Assessment by Health Pod Systems
Authors: Andreoni Giuseppe , Caiani Enrico Gianluca , Castaldini Nicola
Published: December 2021

Health pods are new systems such as small spaces equipped with medical devices where users can measure several biomedical parameters related to their health status and receive other medical services. Their impact on health over a life course could be relevant in defining healthy aging strategies and/or management of chronic diseases and the early detection of possible symptoms related to some common pathologies. The generated data have not only a personal value but even at a community/society level. Health pods also support educational and empowerment actions to enable the 5P medicine approach, and specifically prevention, health promotion, and public health policymaking. This paper aims at defining their taxonomy, conducting a market and typologies survey, and discussing their potential impact in preventive medicine, presenting data of a pilot test carried out placing two health pods in a superstore environment to validate the demand and the participation of people in a prevention campaign. A 57-day period was observed at two sites: the number of free accesses and administered tests was impressive for size and completeness. The test revealed a good picture of the general health status of the population, with satisfying AGE values in the cardiovascular check and stress index through an HRV analysis. The body composition test revealed a small number of overweight subjects, more in males than in females. This pilot confirmed the huge demand for personalized services for improving well-being, health status, and quality of life and the relevance of these solutions for their individual and societal impact in preventive medicine.
Antimicrobial Activity and In Silico Molecular Docking Studies of Pentacyclic Spiro[oxindole-2,3′-pyrrolidines] Tethered with Succinimide Scaffolds
Authors: Askri Sonia , Dbeibia Amal , Mchiri Chadlia , Boudriga Sarra , Knorr Michael , Roulland Emmanuel , Laprévote Olivier , Saffon-Merceron Nathalie , Gharbi Rafik
Published: December 2021

Three-component cascade reactions of (E)-3-arylidene-1-methyl-pyrrolidine-2,5-diones, L-valine and various isatin derivatives are described. A series of 17 spiropyrrolidine derivatives with wide structural complexity and diversity have been thus obtained in moderate to excellent yields under mild reaction conditions. The structure and stereochemistry of these N-heterocyclic cycloadducts has been established by spectroscopic techniques and unambiguously confirmed by a single-crystal X-ray diffraction analysis performed on one derivative. UV-visible spectra have been recorded for all new compounds. Furthermore, the synthesized N-heterocyclic compounds have been screened for their in vitro antibacterial and antifungal activities. Several derivatives exhibited moderate to good activities, comparable to those of the known standard drugs Amphotericin B and Tetracycline. Structural activity relationships (SARs) and molecular docking of the most promising derivatives into the binding sites of glucosamine 6-phosphate synthase (GlcN6P) and methionyl-trna-synthetase (1PFV) were also established. Furthermore, pharmacokinetic studies indicate that the heterocycles exhibit acceptable predictive ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties and good drug ability.
Prediction of Compressive Strength of Fly-Ash-Based Concrete Using Ensemble and Non-Ensemble Supervised Machine-Learning Approaches
Authors: Song Yang , Zhao Jun , Ostrowski Krzysztof Adam , Javed Muhammad Faisal , Ahmad Ayaz , Khan Muhammad Ijaz , Aslam Fahid , Kinasz Roman
Published: December 2021

The utilization of waste material, such as fly ash, in the concrete industry will provide a valuable alternative solution for creating an eco-friendly environment. However, experimental work is time-consuming; employing soft machine learning techniques can accelerate the process of forecasting the strength properties of concrete. Ensemble machine learning modeling using Python Jupyter Notebook was employed in the forecasting of compressive strength (CS) of high-performance concrete. Multilayer perceptron neuron network (MLPNN) and decision tree (DT) were used as individual learning which then ensembled with bagging and boosting to provide strong correlations. Random forest (RF) and gradient boosting regression (GBR) were also used for prediction. A total of 471 data points with input parameters (e.g., cement, fine aggregate, coarse aggregate, superplasticizer, water, days, and fly ash), and an output parameter of compressive strength (CS), were retrieved to train and test the individual learners. Cross-validation with K-fold and statistical error (i.e., MAE, MSE, RMSE, and RMSLE) analysis was applied to check the accuracy of all models. All models showed the best correlation with an ensemble model rather than an individual one. DT with AdaBoost and random forest gave a strong correlation of R2 = 0.89 with fewer errors. Cross-validation results revealed a good response with an error of less than 10 MPa. Thus, ensemble modeling not only trains the data by employing several weak learners but also produces a robust correlation that can then be used to model and predict the mechanical performance of concrete.
Nourishing the Human Holobiont to Reduce the Risk of Non-Communicable Diseases: A Cow’s Milk Evidence Map Example
Authors: Dietert Rodney R. , Coleman Margaret E. , North D. Warner , Stephenson Michele M.
Published: December 2021

The microbiome revolution brought the realization that diet, health, and safety for humans in reality means diet, health, and safety for the human holobiont/superorganism. Eating healthier means much more than just feeding human cells. Our diet must also nourish the combination of our microbiome and our connected physiological systems (e.g., the microimmunosome). For this reason, there has been an interest in returning to ancestral “complete” unprocessed foods enriched in microbes, including raw milks. To contribute to this inevitable “nourishing the holobiont” trend, we introduce a systematic risk–benefit analysis tool (evidence mapping), which facilitates transdisciplinary state-of-the-science decisions that transcend single scientific disciplines. Our prior paper developed an evidence map (a type of risk–benefit mind map) for raw vs. processed/pasteurized human breast milk. In the present paper, we follow with a comprehensive evidence map and narrative for raw/natural vs. processed/pasteurized cow’s milk. Importantly, the evidence maps incorporate clinical data for both infectious and non-communicable diseases and allow the impact of modern agricultural, food management, and medical and veterinary monitoring outcomes to be captured. Additionally, we focus on the impact of raw milks (as “complete” foods) on the microimmunosome, the microbiome-systems biology unit that significantly determines risk of the world’s number one cause of human death, non-communicable diseases.
Effect of Air Purification Systems on Particulate Matter and Airborne Bacteria in Public Buses
Authors: Lee Jae Jung , Hwang Hyemin , Hong Suk Chan , Lee Jae Young
Published: December 2021

The indoor air quality in public transport systems is a major concern in South Korea. Within this context, we investigated the effect of air purification systems on the indoor air quality of intercity buses, one of the most popular transport options in South Korea. Air purifiers were custom designed and equipped with high-efficiency particulate air (HEPA) filters to remove particulate matter and ultraviolet light-emitting diodes (UV-LEDs) to remove airborne bacteria. To investigate the effectiveness of the air purification systems, we compared concentrations of particulate matter (PM2.5 and PM10), airborne bacteria, and carbon dioxide (CO2) in six buses (three with air purification systems and three without) along three bus routes (BUS1, BUS2, BUS3) in Gyeonggi Province, South Korea, between 6 April and 4 May 2021. Compared to the buses without air purification, those with air purification systems showed 34–60% and 25–61% lower average concentrations of PM2.5 and PM10, respectively. In addition, buses with air purification systems had 24–78% lower average airborne bacteria concentrations compared to those without air purification systems (when measured after 30 min of initial purification).
Emission Characteristics and Ozone Formation Potential Assessment of VOCs from Typical Metal Packaging Plants
Authors: Wang Hailin , Xue Song , Hao Run , Fang Li , Nie Lei
Published: December 2021

With the rapid development of metal packaging, volatile organic compounds (VOCs) emissions from the packaging processes are also increasing gradually. It is necessary to research the characteristics of VOCs emissions from such important industrial source and its impact on the possible ozone formation. In this research, three typical metal packaging plants were selected, VOCs emission characteristics were investigated, and their ozone formation potential were evaluated by using maximum incremental reactivity (MIR) coefficient method. The results showed that the VOCs emission characteristics of the selected targets were obviously different. VOCs emitted from plant A and B were mainly oxygenated hydrocarbons, which accounted for 85.02% and 43.17%, respectively. Olefins (62.75%) were the main species of plant C. 2-butanone (82.67%), methylene chloride (23.00%) and ethylene (36.67%) were the major species of plant A, plant B and plant C, respectively. The OFP (ozone formation potential) value of plant B (120.49 mg/m3) was much higher than those values of plant A (643.05 mg/m3) and plant C (3311.73 mg/m3), in which para-xylene, meta-xylene, acetaldehyde and ethylene were the main contributors. The difference in OFP values indicated that water-based ink and water-based coatings should be recommended for large scale application due to less VOCs emission and low ozone formation contribution.
First Steps towards a National Approach for Radon Survey in Romanian Schools
Authors: Bican-Brișan Nicoleta , Dobrei Gabriel-Cristian , Burghele Bety-Denissa , Cucoș (Dinu) Alexandra-Laura
Published: December 2021

Schools are a category of public buildings with a high radon exposure risk, due to their high occupancy factor. In Romania, the elaboration of a methodology for radon measurements in schools is a necessity imposed both by the European legislation and by the relatively high percentage (about 10%) of the mapped territory with a potential increased risk of exposure to the action of ionizing radiation emitted by radon. In order to optimize the design of a national survey aimed to evaluate radon exposure of children in Romanian schools, we conducted a pilot study in two schools in Cluj-Napoca, following the screening measurements carried out in 109 schools and kindergartens from five counties. The specific steps that must be followed were described, taking into account the international protocols and particularities of Romanian territory. The proposed approach could act as a guide for other large buildings and is implicit for the implementation of National Radon Action Plan, approved by HG no. 526/12 July 2018 in accordance with Council Directive 2013/59/EURATOM. The obtained results indicate that a high probability of annual radon concentration above the national reference level is to be expected in schools.
Application of AIRS Soundings to Afternoon Convection Forecasting and Nowcasting at Airports
Authors: Yeh Nan-Ching , Chuang Yao-Chung , Peng Hsin-Shuo , Chen Chih-Ying
Published: December 2021

In Taiwan, the frequency of afternoon convection increases in summer (July and August), and the peak hour of afternoon convection occurs at 1500–1600 local solar time (LST). Afternoon convection events are forecasted based on the atmospheric stability index, as computed from the 0800 LST radiosonde data. However, the temporal and spatial resolution and forecast precision are not satisfactory. This study used the observation data of Aqua satellite overpass near Taiwan around 1–3 h before the occurrence of afternoon convection. Its advantages are that it improves the prediction accuracy and increases the data coverage area, which means that more airports can use results of this research, especially those without radiosondes. In order to determine the availability of Atmospheric Infrared Sounder (AIRS) in Taiwan, 2010–2016 AIRS and radiosonde-sounding data were used to determine the accuracy of AIRS. This study also used 2017–2018 AIRS data to establish K index (KI) and total precipitable water (TPW) thresholds for the occurrence of afternoon convection of four airports in Taiwan. Finally, the KI and TPW were calculated using the independent AIRS atmospheric sounding (2019–2020) to forecast the occurrence of afternoon convection at each airport. The average predictive accuracy rate of the four airports is 84%. Case studies at Hualien Airport show the average predictive accuracy rate of this study is 81.8%, which is 9.1% higher than that of the traditional sounding forecast (72.7%) during the same period. Research results show that using AIRS data to predict afternoon convection in this study could not only increase data coverage area but also improve the accuracy of the prediction effectively.
The Impact of Traffic and Meteorology on Urban Particle Mass and Particle Number Concentrations: Student-Led Studies Using Mobile Measurements before, during, and after the COVID-19 Pandemic Lockdowns
Authors: Klemm Otto , Ahrens Antonia , Arnswald Margarethe , Bethke Raika , Berger David Frederik , Blankenhaus Katharina , Blauth Lisa , Breuer Bettina , Buchholz Sophia , Burek Felix , Ehrnsperger Laura , Funken Sarah , Henninger Ella , Hohl Janik , Jöllenbeck Nadine , Kirgasser Philipp , Kuhls Maike , Paas Bastian , Roters Lea Andrea , Schaller Carsten , Schlüter Hanna
Published: December 2021

A series of student-led research activities were performed using a cargo bicycle equipped with air chemistry instrumentation to study the dynamics of aerosol particles in urban air before, during, and after the COVID-19 lockdown periods. The studies examined a high-traffic route and a low-traffic route around the city center of Münster, Germany. A complex picture emerged for how the particle number concentrations (PN) and particle mass concentrations (PM, specifically PM10) were affected by the day of the week, the route selected, the meteorological conditions, and the traffic intensity. Traffic had the most impact on PN through the multitude of exhaust plumes from motorized vehicles. The impact of traffic on PM10 was rather low, which is also mirrored in the general pattern of the low response of PM10 to the pandemic lockdown in Germany. Instead, PM10 responded more to the day of the week. Presumably, PM10 responds either to a specific traffic component, such as commercial low-duty vehicles, or to other business, such as construction activity. Meteorological conditions exert their impact mostly through the relative humidity, which affects particle growth. As such, future research could examine PN and PM10 responses over all seasons of the year. In any case, this student-led study in which high-resolution data were acquired deepened our understanding and broadened our view on particle dynamics in urban air. Well-trained university graduates will contribute to meeting further challenges in studying and combatting air pollution.
A Study to Explore the Dew Condensation Potential of Cars
Authors: Muselli Marc , Carvajal Danilo , Beysens Daniel A.
Published: December 2021

The metal surfaces of a car exhibit favorable properties for the passive condensation of atmospheric water. Under certain nocturnal climatic conditions (high relative humidity, weak windspeed, and total nebulosity), dew is often observed on cars, and it is appropriate to ask the question of using a vehicle as a standard condenser for estimating the dew yield. In order to see whether cars can be used as reference dew condensers, we report a detailed study of radiative cooling and dew formation on cars in the presence of radiating obstacles and for various windspeeds. Measurements of temperature and condensed dew mass on different car parts (rooftop, front and back hoods, windshield, lateral and back windows, inside and outside air) are compared with the same data obtained on a horizontal, thermally isolated planar film. The paper concludes that heat transfer coefficients, evaluated from temperature and dew yield measurements, are found nearly independent of windspeed and tilt angles. Moreover, this work describes the relation between cooling and dew condensation with the presence or not of thermal isolation. This dependence varies with the surface tilt angle according to the angular dependence of the atmosphere radiation. This work also confirms that cars can be used to estimate the dew yields in a given site. A visual observation scale h = Kn, with h the dew yield (mm) and n = 0, 1 2, 3 an index, which depends whether dew forms or not on rooftop, windshield, and lateral windows, is successfully tested with 8 different cars in 5 sites with three different climates, using K = (0.067 ± 0.0036) mm·day−1.
Predicting and Visualizing STK11 Mutation in Lung Adenocarcinoma Histopathology Slides Using Deep Learning
Authors: Hong Runyu , Liu Wenke , Fenyö David
Published: December 2021

Studies have shown that STK11 mutation plays a critical role in affecting the lung adenocarcinoma (LUAD) tumor immune environment. By training an Inception-Resnet-v2 deep convolutional neural network model, we were able to classify STK11-mutated and wild-type LUAD tumor histopathology images with a promising accuracy (per slide AUROC = 0.795). Dimensional reduction of the activation maps before the output layer of the test set images revealed that fewer immune cells were accumulated around cancer cells in STK11-mutation cases. Our study demonstrated that deep convolutional network model can automatically identify STK11 mutations based on histopathology slides and confirmed that the immune cell density was the main feature used by the model to distinguish STK11-mutated cases.
Genetic and Brain Mechanisms of Addictive Behavior and Neuroadaptation
Authors: Phillips Tamara J.
Published: December 2021

Genetic differences play a role in the susceptibility to addictive drug use, the probability that the use of these drugs will escalate and result in a drug use disorder, and whether relapse to use will occur during or after treatment [...]
Brain Activity after Intermittent Hypoxic Brain Condition in Rats
Authors: Mun Bora , Jang Yun-Chol , Kim Eun-Jong , Kim Ja-Hae , Song Min-Keun
Published: December 2021

Hypoxic brain injury is accompanied by a decrease in various functions. It is also known that obstructive sleep apnea (OSA) can cause hypoxic brain injury. This study aimed to produce a model of an intermittent hypoxic brain condition in rats and determine the activity of the brain according to the duration of hypoxic exposure. Forty male Sprague–Dawley rats were divided into four groups: the control group (n = 10), the 2 h per day hypoxia exposure group (n = 10), the 4 h per day hypoxia exposure group (n = 10), and the 8 h per day hypoxia exposure group (n = 10). All rats were exposed to a hypoxic chamber containing 10% oxygen for five days. Positron emission tomography–computed tomography (PET-CT) brain images were acquired using a preclinical PET-CT scanner to evaluate the activity of brain metabolism. All the rats were subjected to normal conditions. After five days, PET-CT was performed to evaluate the recovery of brain metabolism. Western blot analysis and immunohistochemistry were performed with vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF). The mean SUV was elevated in the 2 h per day and 4 h per day groups, and all brain regions showed increased metabolism except the amygdala on the left side, the auditory cortex on the right side, the frontal association cortex on the right side, the parietal association cortex on the right side, and the somatosensory cortex on the right side immediately after hypoxic exposure. However, there was no difference between 5 days rest after hypoxic exposure and control group. Western blot analysis revealed the most significant immunoreactivity for VEGF in the 2, 4, and 8 h per day groups compared with the control group and quantification of VEGF immunohistochemistry showed more expression in 2 and 4 h per day groups compared with the control group. However, there was no significant difference in immunoreactivity for BDNF among the groups. The duration of exposure to hypoxia may affect the activity of the brain due to angiogenesis after intermittent hypoxic brain conditions in rats.
Cell-Free-DNA-Based Copy Number Index Score in Epithelial Ovarian Cancer—Impact for Diagnosis and Treatment Monitoring
Authors: Braicu Elena Ioana , du Bois Andreas , Sehouli Jalid , Beck Julia , Prader Sonia , Kulbe Hagen , Eiben Bernd , Harter Philipp , Traut Alexander , Pietzner Klaus , Glaubitz Ralf , Ataseven Beyhan , Chekerov Radoslav , Keck Christoph , Winkler Thomas , Heikaus Sebastian , Gellendin Peggy , Schütz Ekkehard , Heitz Florian
Published: December 2021

Background: Chromosomal instability, a hallmark of cancer, results in changes in the copy number state. These deviant copy number states can be detected in the cell-free DNA (cfDNA) and provide a quantitative measure of the ctDNA levels by converting cfDNA next-generation sequencing results into a genome-wide copy number instability score (CNI-Score). Our aim was to determine the role of the CNI-Score in detecting epithelial ovarian cancer (EOC) and its role as a marker to monitor the response to treatment. Methods: Blood samples were prospectively collected from 109 patients with high-grade EOC. cfDNA was extracted and analyzed using a clinical-grade assay designed to calculate a genome-wide CNI-Score from low-coverage sequencing data. Stored data from 241 apparently healthy controls were used as a reference set. Results: Comparison of the CNI-Scores of primary EOC patients versus controls yielded sensitivities of 91% at a specificity of 95% to detect OC, respectively. Significantly elevated CNI-Scores were detected in primary (median: 87, IQR: 351) and recurrent (median: 346, IQR: 1891) blood samples. Substantially reduced CNI-Scores were detected after primary debulking surgery. Using a cut-off of 24, a diagnostic sensitivity of 87% for primary and recurrent EOC was determined at a specificity of 95%. CNI-Scores above this threshold were detected in 21/23 primary tumor (91%), 36/42 of platinum-eligible recurrent (85.7%), and 19/22 of non-platinum-eligible recurrent (86.3%) samples, respectively. Conclusion: ctDNA-quantification based on genomic instability determined by the CNI-Score was a biomarker with high diagnostic accuracy in high-grade EOC. The applied assay might be a promising tool for diagnostics and therapy monitoring, as it requires no a priori information about the tumor.
Survival Outcomes after Hyperthermic Intraperitoneal Chemotherapy for a First Ovarian Cancer Relapse: A Systematic Evidence-Based Review
Authors: Classe Jean-Marc , Asselain Bernard , Campion Loic , Berton Dominique , Frenel Jean-Sébastien , Lécuru Fabrice , Ferron Gwenael , Gladieff Laurence , Bourgin Charlotte , Loaec Cecile
Published: December 2021

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) is routinely used in the treatment of a first ovarian cancer relapse. Methods: This systematic review, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, aimed to assess the quality of scientific proof of the survival benefits of HIPEC, using Medline and Google Scholar. Qualitative analysis using the Oxford CEBM Levels of Evidence 2011 grading is reported. Results: Of 469 articles identified, 23 were included; 15 based on series of patients treated with HIPEC without a control group, and 8 case control series of patients treated with or without HIPEC. The series without a control group showed median overall survival (OS) ranged from 23.5 to 63 months, highlighting a broad standard deviation. Considering the case control series, OS was significantly better in the HIPEC group in 5 studies, and similar in 1. The current review showed considerable heterogeneity and biases, with an Oxford Level of Evidence grading of 4 for 22 selected series and 2 for one. Conclusions: There is no strong evidence to suggest efficacy of HIPEC in improving survival of patients treated for a first relapse of ovarian cancer due to the low quality of the data.
The Role of Conventionally Fractionated Radiotherapy and Stereotactic Radiotherapy in the Treatment of Carcinoid Tumors and Large-Cell Neuroendocrine Cancer of the Lung
Authors: Bilski Mateusz , Mertowska Paulina , Mertowski Sebastian , Sawicki Marcin , Hymos Anna , Niedźwiedzka-Rystwej Paulina , Grywalska Ewelina
Published: December 2021

The occurrence of neuroendocrine tumors among the diagnosed neoplasms is extremely rare and is associated with difficulties in undertaking effective therapy due to the histopathological differentiation of individual subtypes and the scarce clinical data and recommendations found in the literature. The choice of treatment largely depends not only on its type, but also on the location and production of excess hormones by the tumor itself. Common therapeutic approaches include surgical removal of the tumor, the use of chemotherapy, targeted drug therapy, peptide receptor radionuclide therapy, and the use of radiation therapy. This article reviews the current knowledge on the classification and application of radiotherapy in the treatment of lung NETs. Case reports were presented in which treatment with conventional radiotherapy, radical and palliative radiochemotherapy, as well as stereotactic fractionated radiotherapy in the treatment of typical (TC) and atypical (AT) lung carcinoids and large cell neuroendocrine carcinoma (LCNC) were used. We hope that the solutions presented in the literature will allow many radiation oncologists to make the best, often personalized decisions about the therapeutic qualifications of patients.
A 17-Gene Expression Signature for Early Identification of Poor Prognosis in Clear Cell Renal Cell Carcinoma
Authors: Bassanelli Maria , Borro Marina , Roberto Michela , Giannarelli Diana , Giacinti Silvana , Di Martino Simona , Ceribelli Anna , Russo Andrea , Aschelter Annamaria , Scarpino Stefania , Montori Andrea , Pescarmona Edoardo , Tomao Silverio , Simmaco Maurizio , Cognetti Francesco , Milella Michele , Marchetti Paolo
Published: December 2021

The Identification of reliable Biomarkers able to predict the outcome after nephrectomy of patients with clear cell renal cell carcinoma (ccRCC) is an unmet need. The gene expression analysis in tumor tissues represents a promising tool for better stratification of ccRCC subtypes and patients’ evaluation. Methods: In our study we retrospectively analyzed using Next-Generation expression analysis (NanoString), the expression of a gene panel in tumor tissue from 46 consecutive patients treated with nephrectomy for non-metastatic ccRCC at two Italian Oncological Centres. Significant differences in expression levels of selected genes was sought. Additionally, we performed a univariate and a multivariate analysis on overall survival according to Cox regression model. Results: A 17-gene expression signature of patients with a recurrence-free survival (RFS) < 1 year (unfavorable genomic signature (UGS)) and of patients with a RFS > 5 years (favorable genomic signature (FGS)) was identified and resulted in being significantly correlated with overall survival of the patients included in this analysis (HR 51.37, p < 0.0001). Conclusions: The identified Genomic Signatures may serve as potential biomarkers for prognosis prediction of non-metastatic RCC and could drive both follow-up and treatment personalization in RCC management.
Patients’ Experience of Systemic Treatment of Hepatocellular Carcinoma: A Review of the Impact on Quality of Life
Authors: Muzellec Léa , Bourien Héloïse , Edeline Julien
Published: December 2021

Quality of life (QoL) in oncology is an outcome becoming more and more important and relevant to explore. Some studies have demonstrated its prognostic impact in different cancers, such as colorectal, breast, and prostate cancers, but also in hepatocellular carcinoma (HCC). Different tools have been developed for assessing quality of life, some general, such as EORTC QLQ-C30, but also specific tools depending on cancer origin which seem to be more pertinent for patients. Systemic treatments and specific symptoms due to cancer evolution could decrease quality of life. For approval of new systemic treatments, authorities ask for benefit in terms of efficacy but also benefit in quality of life, which is crucial for patients. This review reports data about QoL in HCC, including specific tools used, impact of systemic treatments and prognosis for QoL for HCC patients. Management of adverse events is essential to enhance compliance with treatment and quality of life. Assessing quality of life in clinical trials appears quite systematic, but its application in clinical routine requires development.
Importance of T, NK, CAR T and CAR NK Cell Metabolic Fitness for Effective Anti-Cancer Therapy: A Continuous Learning Process Allowing the Optimization of T, NK and CAR-Based Anti-Cancer Therapies
Authors: Krug Adrien , Martinez-Turtos Adriana , Verhoeyen Els
Published: December 2021

Chimeric antigen receptor (CAR) T and CAR NK cell therapies opened new avenues for cancer treatment. Although original successes of CAR T and CAR NK cells for the treatment of hematological malignancies were extraordinary, several obstacles have since been revealed, in particular their use for the treatment of solid cancers. The tumor microenvironment (TME) is competing for nutrients with T and NK cells and their CAR-expressing counterparts, paralyzing their metabolic effective and active states. Consequently, this can lead to alterations in their anti-tumoral capacity and persistence in vivo. High glucose uptake and the depletion of key amino acids by the TME can deprive T and NK cells of energy and building blocks, which turns them into a state of anergy, where they are unable to exert cytotoxic activity against cancer cells. This is especially true in the context of an immune-suppressive TME. In order to re-invigorate the T, NK, CAR T and CAR NK cell-mediated antitumor response, the field is now attempting to understand how metabolic pathways might change T and NK responses and functions, as well as those from their CAR-expressing partners. This revealed ways to metabolically rewire these cells by using metabolic enhancers or optimizing pre-infusion in vitro cultures of these cells. Importantly, next-generation CAR T and CAR NK products might include in the future the necessary metabolic requirements by improving their design, manufacturing process and other parameters. This will allow the overcoming of current limitations due to their interaction with the suppressive TME. In a clinical setting, this might improve their anti-cancer effector activity in synergy with immunotherapies. In this review, we discuss how the tumor cells and TME interfere with T and NK cell metabolic requirements. This may potentially lead to therapeutic approaches that enhance the metabolic fitness of CAR T and CAR NK cells, with the objective to improve their anti-cancer capacity.
Clearing the Haze: How Does Nicotine Affect Hematopoiesis before and after Birth?
Authors: Cool Taylor , Baena Alessandra Rodriguez y , Forsberg E. Camilla
Published: December 2021

Hematopoiesis is a tightly regulated process orchestrated by cell-intrinsic and cell-extrinsic cues. Over the past several decades, much effort has been focused on understanding how these cues regulate hematopoietic stem cell (HSC) function. Many endogenous key regulators of hematopoiesis have been identified and extensively characterized. Less is known about the mechanisms of long-term effects of environmental toxic compounds on hematopoietic stem and progenitor cells (HSPCs) and their mature immune cell progeny. Research over the past several decades has demonstrated that tobacco products are extremely toxic and pose huge risks to human health by causing diseases like cancer, respiratory illnesses, strokes, and more. Recently, electronic cigarettes have been promoted as a safer alternative to traditional tobacco products and have become increasingly popular among younger generations. Nicotine, the highly toxic compound found in many traditional tobacco products, is also found in most electronic cigarettes, calling into question their purported “safety”. Although it is known that nicotine is toxic, the pathophysiology of disease in exposed people remains under investigation. One plausible contributor to altered disease susceptibility is altered hematopoiesis and associated immune dysfunction. In this review, we focus on research that has addressed how HSCs and mature blood cells respond to nicotine, as well as identify remaining questions.
IL-33, an Alarmin of the IL-1 Family Involved in Allergic and Non Allergic Inflammation: Focus on the Mechanisms of Regulation of Its Activity
Authors: Cayrol Corinne
Published: December 2021

Interleukin-33 (IL-33) is a member of the interleukin-1 (IL-1) family that is expressed in the nuclei of endothelial and epithelial cells of barrier tissues, among others. It functions as an alarm signal that is released upon tissue or cellular injury. IL-33 plays a central role in the initiation and amplification of type 2 innate immune responses and allergic inflammation by activating various target cells expressing its ST2 receptor, including mast cells and type 2 innate lymphoid cells. Depending on the tissue environment, IL-33 plays a wide variety of roles in parasitic and viral host defense, tissue repair and homeostasis. IL-33 has evolved a variety of sophisticated regulatory mechanisms to control its activity, including nuclear sequestration and proteolytic processing. It is involved in many diseases, including allergic, inflammatory and infectious diseases, and is a promising therapeutic target for the treatment of severe asthma. In this review, I will summarize the literature around this fascinating pleiotropic cytokine. In the first part, I will describe the basics of IL-33, from the discovery of interleukin-33 to its function, including its expression, release and signaling pathway. The second part will be devoted to the regulation of IL-33 protein leading to its activation or inactivation.
Strategies to Optimize Adherence in Patients with Mycosis Fungoides
Authors: Chan Warren H. , Lewis Daniel J. , Duvic Madeleine , Feldman Steven R.
Published: December 2021

Patient adherence to medications for common skin conditions has been extensively studied over the past two decades, and suboptimal adherence is a primary contributor to treatment failure. The impact of sub-par adherence in cutaneous T-cell lymphoma (CTCL) patients has been largely unexplored, and promoting adherence in this patient population may represent a promising area of consideration for improving treatment outcomes. We apply patient adherence strategies that have been studied in dermatology to CTCL and provide concrete examples of how these strategies can be used to improve adherence in the CTCL setting. Through the implementation of small changes in how we present and counsel about therapeutic options to our patients, we can maximize patient adherence, which has the potential to optimize therapy regimens and reduce treatment failure.
Heat Shock Protein 22 in Physiological and Pathological Hearts: Small Molecule, Large Potentials
Authors: Sun Xiaonan , Siri Sharadhi , Hurst Amirah , Qiu Hongyu
Published: December 2021

Small heat shock protein 22 (HSP22) belongs to the superfamily of heat shock proteins and is predominantly expressed in the heart, brain, skeletal muscle, and different types of cancers. It has been found that HSP22 is involved in variant cellular functions in cardiomyocytes and plays a vital role in cardiac protection against cardiomyocyte injury under diverse stress. This review summarizes the multiple functions of HSP22 in the heart and the underlying molecular mechanisms through modulating gene transcription, post-translational modification, subcellular translocation of its interacting proteins, and protein degradation, facilitating mitochondrial function, cardiac metabolism, autophagy, and ROS production and antiapoptotic effect. We also discuss the association of HSP22 in cardiac pathologies, including human dilated cardiomyopathy, pressure overload-induced heart failure, ischemic heart diseases, and aging-related cardiac metabolism disorder. The collected information would provide insights into the understanding of the HSP22 in heart diseases and lead to discovering the therapeutic targets.
Combined Use of Whole Exome Sequencing and CRISPR/Cas9 to Study the Etiology of Non-Obstructive Azoospermia: Demonstration of the Dispensable Role of the Testis-Specific Genes C1orf185 and CCT6B
Authors: Cazin Caroline , Neirijnck Yasmine , Loeuillet Corinne , Wehrli Lydia , Kühne Françoise , Lordey Isabelle , Mustapha Selima Fourati Ben , Bouker Amin , Zouari Raoudha , Thierry-Mieg Nicolas , Nef Serge , Arnoult Christophe , Ray Pierre F. , Kherraf Zine-Eddine
Published: December 2021

The genetic landscape of male infertility is highly complex. It is estimated that at least 4000 genes are involved in human spermatogenesis, but only few have so far been extensively studied. In this study, we investigated by whole exome sequencing two cases of idiopathic non-obstructive azoospermia (NOA) due to severe hypospermatogenesis. After variant filtering and prioritizing, we retained for each patient a homozygous loss-of-function (LoF) variant in a testis-specific gene, C1orf185 (c.250C>T; p.Gln84Ter) and CCT6B (c.615-2A>G), respectively. Both variants are rare according to the gnomAD database and absent from our local control cohort (n = 445). To verify the implication of these candidate genes in NOA, we used the CRISPR/Cas9 system to invalidate the mouse orthologs 4930522H14Rik and Cct6b and produced two knockout (KO) mouse lines. Sperm and testis parameters of homozygous KO adult male mice were analyzed and compared with those of wild-type animals. We showed that homozygous KO males were fertile and displayed normal sperm parameters and a functional spermatogenesis. Overall, these results demonstrate that not all genes highly and specifically expressed in the testes are essential for spermatogenesis, and in particular, we conclude that bi-allelic variants of C1orf185 and CCT6B are most likely not to be involved in NOA and male fertility.
Selectivity of mTOR-Phosphatidic Acid Interactions Is Driven by Acyl Chain Structure and Cholesterol
Authors: Żelasko Jolanta , Czogalla Aleksander
Published: December 2021

The need to gain insights into the molecular details of peripheral membrane proteins’ specificity towards phosphatidic acid (PA) is undeniable. The variety of PA species classified in terms of acyl chain length and saturation translates into a complicated, enigmatic network of functional effects that exert a critical influence on cell physiology. As a consequence, numerous studies on the importance of phosphatidic acid in human diseases have been conducted in recent years. One of the key proteins in this context is mTOR, considered to be the most important cellular sensor of essential nutrients while regulating cell proliferation, and which also appears to require PA to build stable and active complexes. Here, we investigated the specific recognition of three physiologically important PA species by the mTOR FRB domain in the presence or absence of cholesterol in targeted membranes. Using a broad range of methods based on model lipid membrane systems, we elucidated how the length and saturation of PA acyl chains influence specific binding of the mTOR FRB domain to the membrane. We also discovered that cholesterol exerts a strong modulatory effect on PA-FRB recognition. Our data provide insight into the molecular details of some physiological effects reported previously and reveal novel mechanisms of fine-tuning the signaling cascades dependent on PA.
GILZ as a Regulator of Cell Fate and Inflammation
Authors: Bruscoli Stefano , Riccardi Carlo , Ronchetti Simona
Published: December 2021

One of the human body’s initial responses to stress is the adrenal response, involving the release of mediators that include adrenaline and glucocorticoids (GC). GC are involved in controlling the inflammatory and immune response mechanisms. Of these, the molecular mechanisms that contribute to anti-inflammatory effects warrant more investigation. Previously, we found that GC induced GILZ (glucocorticoid-induced leucine zipper) quickly and widely in thymocytes, T lymphocytes, and other leukocytes. GILZ regulates the activation of cells and is an essential mediator of endogenous GC and the majority of GC anti-inflammatory effects. Further research in this regard could lead to the development of an anti-inflammatory treatment that yields the therapeutic outcomes of GC but without their characteristic adverse effects. Here, we examine the mechanisms of GILZ in the context of GC. Specifically, we review its role in the proliferation and differentiation of cells and in apoptosis. We also examine its involvement in immune cells (macrophages, neutrophils, dendritic cells, T and B lymphocytes), and in non-immune cells, including cancer cells. In conclusion, GILZ is an anti-inflammatory molecule that could mediate the immunomodulatory activities of GC, with less adverse effects, and could be a target molecule for designing new therapies to treat inflammatory diseases.
Alterations in B Cell and Follicular T-Helper Cell Subsets in Patients with Acute COVID-19 and COVID-19 Convalescents
Authors: Kudryavtsev Igor V. , Arsentieva Natalia A. , Batsunov Oleg K. , Korobova Zoia R. , Khamitova Irina V. , Isakov Dmitrii V. , Kuznetsova Raisa N. , Rubinstein Artem A. , Stanevich Oksana V. , Lebedeva Aleksandra A. , Vorobyov Evgeny A. , Vorobyova Snejana V. , Kulikov Alexander N. , Sharapova Maria A. , Pevtcov Dmitrii E. , Totolian Areg A.
Published: December 2021

Background. Humoral immunity requires interaction between B cell and T follicular helper cells (Tfh) to produce effective immune response, but the data regarding a role of B cells and Tfh in SARS-CoV-2 defense are still sparse. Methods. Blood samples from patients with acute COVID-19 (n = 64), convalescents patients who had specific IgG to SARS-CoV-2 N-protein (n = 55), and healthy donors with no detectable antibodies to any SARS-CoV-2 proteins (HC, n = 44) were analyses by multicolor flow cytometry. Results. Patients with acute COVID-19 showed decreased levels of memory B cells subsets and increased proportion plasma cell precursors compared to HC and COVID-19 convalescent patients, whereas for the latter the elevated numbers of virgin naïve, Bm2′ and “Bm3+Bm4” was found if compared with HC. During acute COVID-19 CXCR3+CCR6− Tfh1-like cells were decreased and the levels of CXCR3−CCR6+ Tfh17-like were increased then in HC and convalescent patients. Finally, COVID-19 convalescent patients had increased levels of Tfh2-, Tfh17- and DP Tfh-like cells while comparing their amount with HC. Conclusions. Our data indicate that COVID-19 can impact the humoral immunity in the long-term.
Enhancement of sp3 C Fraction in Diamond-like Carbon Coatings by Cryogenic Treatment
Authors: Peng Jihua , Liao Jingwen , Peng Yinglong , Xiao Yang , Huang Jinhai , Li Liejun
Published: December 2021

Diamond-like carbon (DLC) coatings deposited onto high-speed-steel surfaces were subjected to deep cryogenic treatment (DCT) at temperatures of −120 to −196 °C to investigate the evolution of microstructure, bonding structure, and mechanical properties. The surface morphology and the bonding structure of the DLC coatings were studied using scanning electron microscopy, transmission electron microscopy, micro-Raman spectroscopy, and X-ray photoelectron spectroscopy. It is found that DCT affects the surface morphology, especially the size and the height of the aggregates. For those DLCs with more than 50% sp3 C fraction, the sp2 C → sp3 C transformation occurred in coatings treated at a temperature of −120 to −160 °C; and the maximum fraction of sp3 C was obtained after treatment at −140 °C. Almost keeping the wear resistance of DLCs, DCT can improve the adhesion strength, and surface hardness. The findings of this study indicate that DCT will be a potential post-treatment method to tune the microstructure and mechanical performance of DLC coatings.
COVID-19 Pandemic: How Effective Are Preventive Control Measures and Is a Complete Lockdown Justified? A Comparison of Countries and States
Authors: Fuss Franz Konstantin , Weizman Yehuda , Tan Adin Ming
Published: December 2021

For fighting the COVID-19 pandemic, countries used control measures of different severity, from “relaxed” to lockdown. Drastic lockdown measures are considered more effective but also have a negative impact on the economy. When comparing the financial value of lost lives to the losses of an economic disaster, the better option seems to be lockdown measures. We developed a new parameter, the effectiveness of control measures, calculated from the 2nd time derivative of daily case data, for 92 countries, states and provinces. We compared this parameter, and also the mortality during and after the effective phase, for countries with and without lockdowns measures by means of the Mann–Whitney test. We did not find any statistically significant difference in the effectiveness between countries with and without lockdowns (p > 0.76). There was also no significant difference in mortality during the effective phase (p > 0.1); however, a significant difference after the effective phase, with higher mortality for lockdown countries, was identified. The effectiveness correlated well with a parameter derived from the reproductive number (R2 = 0.9480). The average duration of the effective phase was 17.3 ± 10.5 days. The results indicated that lockdown measures are not necessarily superior to relaxed measures, which in turn are not necessarily a recipe for failure. Relaxed measures are, however, more economy-friendly.
Expression Profiles of Long Non-Coding RNA GAS5 and MicroRNA-222 in Younger AML Patients
Authors: Pavlovic Djordje , Tosic Natasa , Zukic Branka , Pravdic Zlatko , Vukovic Nada Suvajdzic , Pavlovic Sonja , Gasic Vladimir
Published: December 2021

Acute myeloid leukemia (AML) is a heterogeneous malignant disease both on clinical and genetic levels. AML has poor prognosis and, therefore, there is a constant need to find new prognostic markers, as well as markers that can be used as targets for innovative therapeutics. Recently, the search for new biomarkers has turned researchers’ attention towards non-coding RNAs, especially long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs). We investigated the expression level of growth arrest-specific transcript 5 (GAS5) lncRNA in 94 younger AML patients, and also the expression level of miR-222 in a cohort of 39 AML patients with normal karyotype (AML-NK), in order to examine their prognostic potential. Our results showed that GAS5 expression level in AML patients was lower compared to healthy controls. Lower GAS5 expression on diagnosis was related to an adverse prognosis. In the AML-NK group patients had higher expression of miR-222 compared to healthy controls. A synergistic effect of GAS5low/miR-222high status on disease prognosis was not established. This is the first study focused on examining the GAS5 and miR-222 expression pattern in AML patients. Its initial findings indicate the need for further investigation of these two non-coding RNAs, their potential roles in leukemogenesis, and the prognosis of AML patients.