bluuebunny/crossref_metadata_2025 huggingface dataset:
Near-Term Suitability Assessment of Deploying DAC System at Airport: A Case Study of 52 Large Airports in China
Authors: Wang Feiyin , Wang Pengtao , Xu Mao , Li Xiaoyu , Tan Wei , Li Hang
Published: June 2023

This study is the first to propose the deployment of direct air capture (DAC) systems at large airports to provide solutions for achieving carbon neutrality in aviation transportation. Here, an estimating model for carbon dioxide (CO2) emissions in the landing and take-off (LTO) phase of large airports was developed, and the suitability of deploying DAC systems at airports was evaluated by the analytic hierarchy process (AHP). This study found that the annual CO2 emissions of 52 large airports in the LTO phase are about 23 Mt, accounting for about 23% of the total CO2 emissions of civil aviation in China. The four dimensions of airport transportation conditions, meteorological conditions, space resources, and security levels had a decreasing impact on the deployment of DAC systems in that order. The airports with suitable DAC systems are mainly located in the Yangtze River Delta, the Pearl River Delta, and the Chengdu-Chongqing Airport Cluster. This study provides a theoretical basis for the deployment of DAC systems at airports, which provides new CO2 emission reduction solutions for the aviation transportation industry.
Analysis of Spatio-Temporal Characteristics of Visibility in the Yellow and Bohai Seas Based on Observational Data
Authors: Zhang Lei , Xu Mei , Qiu Xiaobin , Zhang Dongbin , Liao Rongwei , Fang Xiaoyi , Wu Bingui , Meng Fanchao
Published: June 2023

In the Yellow and Bohai Seas, the detailed characteristics of visibility are analyzed based on automatic hourly observation data of marine visibility between 2019 and 2021. The results show that the annual average visibility in the Yellow and Bohai Seas is 13.346 km. The average visibility at high latitudes is higher than that at low latitudes in the Yellow and Bohai Seas. The low visibility area is mainly distributed in the southwest of the Yellow Sea. There are obvious seasonal differences in visibility in the Yellow and Bohai Seas. Visibility is high from September to November, with maximum values in October. Visibility is lowest in July when the maximum visibility is low and the minimum visibility is high. The visibility in spring is overall relatively low, and the areas of low visibility appear in the southwest of the Yellow Sea. The visibility in autumn is overall relatively high, and the areas of high visibility occur in the northern part of the Bohai and Yellow Seas. The visibility has significant intraday variation. The visibility around sunset is significantly higher than that around sunrise. The hourly visibility is low between 4:00 and 9:00, with the lowest visibility most likely around 7:00. The hourly visibility is high between 16:00 and 21:00, with the highest visibility most likely around 18:00. Low visibility occurs frequently between November and April, most of all in March. Low visibility most often occurs between 4:00 and 7:00. Low visibility may occur at any time between November and April, and also in mornings between May and August. It occurs less often at other times.
Profiling of Aerosols and Clouds over High Altitude Urban Atmosphere in Eastern Himalaya: A Ground-Based Observation Using Raman LIDAR
Authors: Bhattacharyya Trishna , Chatterjee Abhijit , Das Sanat K. , Singh Soumendra , Ghosh Sanjay K.
Published: June 2023

Profiles of aerosols and cloud layers have been investigated over a high-altitude urban atmosphere in the eastern Himalayas in India, for the first time, using a Raman LIDAR. The study was conducted post-monsoon season over Darjeeling (latitude 27°01′ N longitude 88°36′ E, 2200 masl), a tourist destination in north-eastern India. In addition to the aerosols and cloud characterization and atmospheric boundary layer detection, the profile of the water vapor mixing ratio has also been analyzed. Effects of atmospheric dynamics have been studied using the vertical profiles of the normalized standard deviation of RCS along with the water vapor mixing ratio. The aerosol optical characteristics below and above the Atmospheric Boundary Layer (ABL) region were studied separately, along with the interrelation of their optical and microphysical properties with synoptic meteorological parameters. The backscatter coefficient and the extinction coefficient were found in the range from 7.15×10−10 m−1 sr−1 to 3.01×10−5 m−1 sr−1 and from 1.02×10−5 m−1 to 2.28×10−3 m−1, respectively. The LIDAR ratio varies between 3.9 to 78.39 sr over all altitudes. The variation of the linear depolarization ratio from 0.19 to 0.32 indicates the dominance, of non-spherical particles. The periodicity observed in different parameters may be indicative of atmospheric wave phenomena. Cloud parameters, such as scattering coefficients, top and bottom height, and optical depth for different cloud phases, have been evaluated. A co-located Micro Rain Radar has been used with LIDAR for cloud life cycle study.
Hydrogel Coating Optimization to Augment Engineered Soft Tissue Mechanics in Tissue-Engineered Blood Vessels
Authors: Wonski Bryan T. , Fisher Bruce , Lam Mai T.
Published: June 2023

Tissue engineering has the advantage of replicating soft tissue mechanics to better simulate and integrate into native soft tissue. However, soft tissue engineering has been fraught with issues of insufficient tissue strength to withstand physiological mechanical requirements. This factor is due to the lack of strength inherent in cell-only constructs and in the biomaterials used for soft tissue engineering and limited extracellular matrix (ECM) production possible in cell culture. To address this issue, we explored the use of an ECM-based hydrogel coating to serve as an adhesive tool, as demonstrated in vascular tissue engineering. The efficacy of cells to supplement mechanical strength in the coating was explored. Specifically, selected coatings were applied to an engineered artery tunica adventitia to accurately test their properties in a natural tissue support structure. Multiple iterations of three primary hydrogels with and without cells were tested: fibrin, collagen, and gelatin hydrogels with and without fibroblasts. The effectiveness of a natural crosslinker to further stabilize and strengthen the hydrogels was investigated, namely genipin extracted from the gardenia fruit. We found that gelatin crosslinked with genipin alone exhibited the highest tensile strength; however, fibrin gel supported cell viability the most. Overall, fibrin gel coating without genipin was deemed optimal for its balance in increasing mechanical strength while still supporting cell viability and was used in the final mechanical and hydrodynamic testing assessments. Engineered vessels coated in fibrin hydrogel with cells resulted in the highest tensile strength of all hydrogel-coated groups after 14 d in culture, demonstrating a tensile strength of 11.9 ± 2.91 kPa, compared to 5.67 ± 1.37 kPa for the next highest collagen hydrogel group. The effect of the fibrin hydrogel coating on burst pressure was tested on our strongest vessels composed of human aortic smooth muscle cells. A significant increase from our previously reported burst pressure of 51.3 ± 2.19 mmHg to 229 ± 23.8 mmHg was observed; however, more work is needed to render these vessels compliant with mechanical and biological criteria for blood vessel substitutes.
Real-World Endoscopic and Histologic Outcomes in Ulcerative Colitis Patients: A Retrospective Cohort Study
Authors: State Monica , Balanescu Paul , Voiosu Theodor , Bengus Andreea , Voiosu Andrei , Coman Andrei , Mustatea Petronel , Negreanu Lucian , Mateescu Radu Bogdan , Popp Cristiana
Published: June 2023

Background: Histologic activity has emerged as an aspirational therapeutic goal in ulcerative colitis management. It is not yet a formal treatment target in ulcerative colitis. However, it could be used as an adjunct to mucosal healing to represent a deeper level of healing. We investigated mucosal and histologic remission rates and potential predictors of these outcomes in a cohort of UC patients. Methods: We conducted a retrospective analysis of data collected from UC patients enrolled in an ongoing prospective cohort study. Mucosal healing was defined as Mayo endoscopic score = 0. Results: A total of 131 patients with ulcerative colitis were enrolled in our study and were prospectively followed for a median length of 2 years (range 0–5 years), totaling 266 study visits. Mucosal healing was recorded for 27 patients at 70 (26%) different study visits. For patients with mucosal healing, histologic remission was achieved in 18/27 (66%) patients. On univariate analysis, sustained clinical remission, SIBDQ scores ≥ 5.5, CRP ≤ 5 mg/dL and absence of corticotherapy were associated with mucosal healing and SIBDQ scores ≥ 5.5 and CRP ≤ 5 mg/dL with histologic healing, respectively. After logistic regression analysis, none of the investigated factors were associated with mucosal and histologic healing. The number of CD8+ intraepithelial lymphocytes (IELs) was significantly greater than the number of CD4+ IELs in periods of disease activity, as well as during mucosal healing (p < 0.01 in both cases). Conclusions: Mucosal healing and histologic remission rates are low in real-life settings. The results of univariate analysis indicate that a good quality of life (SIBDQ score) and normal inflammatory markers (CRP) are associated with mucosal and histologic healing. However, frequently used patient- and disease-related factors, including mucosal healing, are not reliable predictors for histologic remission. Greater CD8+ lymphocyte involvement and higher CD8+/CD4+ distribution can have a meaningful impact on understanding the pathogenesis and natural history of ulcerative colitis, as well as future treatment options for lymphocyte-targeting medications.
Trajectory of Post-COVID Self-Reported Fatigue and Dyspnoea in Individuals Who Had Been Hospitalized by COVID-19: The LONG-COVID-EXP Multicenter Study
Authors: Fernández-de-las-Peñas César , Cancela-Cilleruelo Ignacio , Rodríguez-Jiménez Jorge , Fuensalida-Novo Stella , Martín-Guerrero José D. , Pellicer-Valero Oscar J. , de-la-Llave-Rincón Ana I.
Published: June 2023

Fatigue and dyspnoea are common post-COVID symptoms. The aim of this study was to apply Sankey plots and exponential bar plots for visualizing the evolution and trajectory of post-COVID fatigue and dyspnoea symptoms in a cohort of previously hospitalized COVID-19 survivors. A total of 1266 previously hospitalized patients due to COVID-19 participated in this multicentre study. They were assessed at hospital admission (T0), 8.4 months (T1), 13.2 months (T2) and 18.3 months (T3) after hospital discharge and were asked about the presence of self-reported fatigue or dyspnoea symptoms. Fatigue was defined as a self-perceived feeling of constant tiredness and/or weakness whereas dyspnoea was defined as a self-perceived feeling of shortness of breath at rest. We specifically asked for fatigue and dyspnoea that participants attributed to the infection. Clinical/hospitalization data were collected from hospital medical records. The prevalence of post-COVID fatigue was 56.94% (n = 721) at T1, 52.31% (n = 662) at T2 and 42.66% (n = 540) at T3. The prevalence of dyspnoea at rest decreased from 28.71% (n = 363) at hospital admission (T0), to 21.29% (n = 270) at T1, to 13.96% (n = 177) at T2 and 12.04% (n = 153) at T3. The Sankey plots revealed that 469 (37.08%) and 153 (12.04%) patients exhibited fatigue and dyspnoea at all follow-up periods. The recovery exponential curves show a decreased prevalence trend, showing that fatigue and dyspnoea recover the following three years after hospitalization. The regression models revealed that the female sex and experiencing the symptoms (e.g., fatigue, dyspnoea) at T1 were factors associated with the presence of post-COVID fatigue or dyspnoea at T2 and T3. The use of Sankey plots shows a fluctuating evolution of post-COVID fatigue and dyspnoea during the first two years after infection. In addition, exponential bar plots revealed a decreased prevalence of these symptoms during the first years after. The female sex is a risk factor for the development of post-COVID fatigue and dyspnoea.
SGLT2 Inhibitors as Potential Anticancer Agents
Authors: Basak Debasish , Gamez David , Deb Subrata
Published: June 2023

Sodium-glucose cotransporter 2 (SGLT2) serves as a critical glucose transporter that has been reported to be overexpressed in cancer models, followed by increased glucose uptake in both mice and humans. Inhibition of its expression can robustly thwart tumor development in vitro and in vivo. SGLT2 inhibitors are a comparatively new class of antidiabetic drugs that have demonstrated anticancer effects in several malignancies, including breast, liver, pancreatic, thyroid, prostate, and lung cancers. This review aims to assess the extent of SGLT involvement in different cancer cell lines and discuss the pharmacology, mechanisms of action, and potential applications of SGLT2 inhibitors to reduce tumorigenesis and its progression. Although these agents display a common mechanism of action, they exhibit distinct affinity towards the SGLT type 2 transporter compared to the SGLT type 1 transporter and varying extents of bioavailability and half-lives. While suppression of glucose uptake has been attributed to their primary mode of antidiabetic action, SGLT2 inhibitors have demonstrated several mechanistic ways to combat cancer, including mitochondrial membrane instability, suppression of β-catenin, and PI3K-Akt pathways, increase in cell cycle arrest and apoptosis, and downregulation of oxidative phosphorylation. Growing evidence and ongoing clinical trials suggest a potential benefit of combination therapy using an SGLT2 inhibitor with the standard chemotherapeutic regimen. Nevertheless, further experimental and clinical evidence is required to characterize the expression and role of SGLTs in different cancer types, the activity of different SGLT subtypes, and their role in tumor development and progression.
Measuring Mitochondrial Oxygen Tension during Red Blood Cell Transfusion in Chronic Anemia Patients: A Pilot Study
Authors: Ubbink Rinse , Streng Lucia W. J. M. , Raat Nicolaas J. H. , Harms Floor A. , te Boekhorst Peter A. W. , Stolker Robert J. , Mik Egbert G.
Published: June 2023

In light of the associated risks, the question has been raised whether the decision to give a blood transfusion should solely be based on the hemoglobin level. As mitochondria are the final destination of oxygen transport, mitochondrial parameters are suggested to be of added value. The aims of this pilot study were to investigate the effect of a red blood cell transfusion on mitochondrial oxygenation as measured by the COMET device in chronic anemia patients and to explore the clinical usability of the COMET monitor in blood transfusion treatments, especially the feasibility of performing measurements in an outpatient setting. To correct the effect of volume load on mitochondrial oxygenation, a red blood cell transfusion and a saline infusion were given in random order. In total, 21 patients were included, and this resulted in 31 observations. If patients participated twice, the order of infusion was reversed. In both the measurements wherein a blood transfusion was given first and wherein 500 mL of 0.9% saline was given first, the median mitochondrial oxygen tension decreased after red blood cell transfusion. The results of this study have strengthened the need for further research into the effect of blood transfusion tissue oxygenation and the potential role of mitochondrial parameters herein.
Simultaneous Determination of Uric Acid and Caffeine by Flow Injection Using Multiple-Pulse Amperometry
Authors: Wong Ademar , Santos Anderson M. , Feitosa Maria H. A. , Fatibello-Filho Orlando , Moraes Fernando C. , Sotomayor Maria D. P. T.
Published: June 2023

The present study reports the development and application of a flow injection analysis (FIA) system for the simultaneous determination of uric acid (UA) and caffeine (CAF) using cathodically pretreated boron-doped diamond electrode (CPT-BDD) and multiple-pulse amperometry (MPA). The electrochemical profiles of UA and CAF were analyzed via cyclic voltammetry in the potential range of 0.20–1.7 V using 0.10 mol L−1 H2SO4 solution as supporting electrolyte. Under optimized conditions, two oxidation peaks at potentials of 0.80 V (UA) and 1.4 V (CAF) were observed; the application of these potentials using multiple-pulse amperometry yielded concentration linear ranges of 5.0 × 10−8–2.2 × 10−5 mol L−1 (UA) and 5.0 × 10−8–1.9 × 10−5 mol L−1 (CAF) and limits of detection of 1.1 × 10−8 and 1.3 × 10−8 mol L−1 for UA and CAF, respectively. The proposed method exhibited good repeatability and stability, and no interference was detected in the electrochemical signals of UA and CAF in the presence of glucose, NaCl, KH2PO4, CaCl2, urea, Pb, Ni, and Cd. The application of the FIA-MPA method for the analysis of environmental samples resulted in recovery rates ranging between 98 and 104%. The results obtained showed that the BDD sensor exhibited a good analytical performance when applied for CAF and UA determination, especially when compared to other sensors reported in the literature.
Liquid Metal Flexible EMG Gel Electrodes for Gesture Recognition
Authors: Bai Yanru , Li Xiaoqing , Zheng Chengcai , Guo Rui , Li Xisheng
Published: June 2023

Gesture recognition has been playing an increasingly important role in the field of intelligent control and human–computer interaction. Gesture recognition technology based on electromyography (EMG) with high accuracy has been widely applied. However, conventional rigid EMG electrodes do not fit the mechanical properties of human skin. Therefore, rigid EMG electrodes are easily influenced by body movements, and uncomfortable to wear and use for a long time. To solve these problems, a stretchable EMG electrode based on liquid metal nanoparticles was developed in this research. It is conformal with human skin because of its similar mechanical properties to skin. Liquid metal nanoparticles mixed in polymer can be connected to each other to form conductive circuits when pressed by mechanical force. Therefore, this preparation method of liquid metal flexible gel electrodes is low-cost and can be fabricated largely. Moreover, the liquid metal flexible gel electrodes have great stretch ability. Their resistance increases slightly at maximum strain state. Based on these advantages, the flexible gel electrodes are applied to arm to collect EMG signals generated by human hand movements. In addition, the signals are analyzed by artificial intelligence algorithm to realize accurate gesture recognition.
Multiple Sclerosis—A Demyelinating Disorder and Its Dental Considerations—A Literature Review with Own Case Report
Authors: Al Johani Khalid , Fudah Mashael , Al-Zahrani Mohammad , Abed Hassan , Srivastava Kumar Chandan , Shrivastava Deepti , Cicciù Marco , Minervini Giuseppe
Published: June 2023

Multiple sclerosis (MS) is a chronic, autoimmune condition that primarily affects the myelin sheath covering the neurons of the central nervous system, including those of the brain and spinal cord. Although the etiology is not completely understood, various factors, such as genetic infections and environmental background, play a role in the pathogenesis. Repeated active episodes of MS characterized with marked inflammation results in the scarring of particular nerve segments, and eventually results in functional impairment over a period of time. Based on the clinical course of the disease, four clinical types of MS have been identified, with the relapsing–remitting type being the commonest. MS is known to occur more commonly in females in the age group of 20–40 years. Dysarthria, fatigue, muscle spasm, and numbness are the common presenting symptoms of MS. Diagnosis is generally achieved with MRI brain scans, showing demyelination plaques and lumbar puncture. Treatment of MS’s acute phase includes high doses of corticosteroids; whereas preventive treatment of MS includes the prescription of immunosuppressive therapy, including biologics. A large group of MS patients present with oral manifestations, including dysphagia, dysarthria, temporomandibular joint (TMJ) disturbances, facial palsy, and chronic periodontal diseases. Other typical oral manifestations seen in MS patients include trigeminal neuralgia, paresthesia, or orofacial pain. Dental treatment and following drug prescription needs to be tailored to each patient, as there is a possibility of drug interactions. This paper presents a comprehensive, updated review of MS, with emphasis on oral manifestations and dental considerations. Additionally, it presents a case of a 40-year-old female diagnosed with MS that was presented to a dental hospital. The report discusses the oral manifestations and dental management.
Hypothalamus and Post-Traumatic Stress Disorder: A Review
Authors: Raise-Abdullahi Payman , Meamar Morvarid , Vafaei Abbas Ali , Alizadeh Maryam , Dadkhah Masoomeh , Shafia Sakineh , Ghalandari-Shamami Mohadeseh , Naderian Ramtin , Afshin Samaei Seyed , Rashidy-Pour Ali
Published: June 2023

Humans have lived in a dynamic environment fraught with potential dangers for thousands of years. While fear and stress were crucial for the survival of our ancestors, today, they are mostly considered harmful factors, threatening both our physical and mental health. Trauma is a highly stressful, often life-threatening event or a series of events, such as sexual assault, war, natural disasters, burns, and car accidents. Trauma can cause pathological metaplasticity, leading to long-lasting behavioral changes and impairing an individual’s ability to cope with future challenges. If an individual is vulnerable, a tremendously traumatic event may result in post-traumatic stress disorder (PTSD). The hypothalamus is critical in initiating hormonal responses to stressful stimuli via the hypothalamic–pituitary–adrenal (HPA) axis. Linked to the prefrontal cortex and limbic structures, especially the amygdala and hippocampus, the hypothalamus acts as a central hub, integrating physiological aspects of the stress response. Consequently, the hypothalamic functions have been attributed to the pathophysiology of PTSD. However, apart from the well-known role of the HPA axis, the hypothalamus may also play different roles in the development of PTSD through other pathways, including the hypothalamic–pituitary–thyroid (HPT) and hypothalamic–pituitary–gonadal (HPG) axes, as well as by secreting growth hormone, prolactin, dopamine, and oxytocin. This review aims to summarize the current evidence regarding the neuroendocrine functions of the hypothalamus, which are correlated with the development of PTSD. A better understanding of the role of the hypothalamus in PTSD could help develop better treatments for this debilitating condition.
Is Social Training Delivered with a Head-Mounted Display Suitable for Patients with Hereditary Ataxia?
Authors: Malerba Giorgia , Bellazzecca Silvia , Urgesi Cosimo , Butti Niccolò , D’Angelo Maria Grazia , Diella Eleonora , Biffi Emilia
Published: June 2023

Social cognition is fundamental in everyday life to understand “others’ behavior”, which is a key feature of social abilities. Previous studies demonstrated the efficacy of a rehabilitative intervention in semi-immersive virtual reality (VR) controlled by whole-body motion to improve the ability of patients with cerebellar disorders to predict others’ intentions (VR-SPIRIT). Patients with severe ataxia that have difficulties at multiple levels of social processing could benefit from this intervention in terms of improving their social prediction skills, but they may have difficulties in controlling VR with whole-body movements. Therefore, we implemented VR-SPIRIT on a wearable, affordable, and easy-to-use technology, such as the Oculus Quest, a head-mounted display. The aim of this work was to evaluate the usability and tolerability of this VR application. We recruited 10 patients (37.7 ± 14.8 years old, seven males) with different types of hereditary ataxia who performed a single VR-SPIRIT session using the Oculus Quest viewer. After the session, patients answered a series of questionnaires to investigate the overall usability of the system and its potential effects in terms of cyber sickness. The preliminary results demonstrated system usability and tolerability. Indeed, only three patients did not complete the session due to different problems (dizziness, nausea, and boredom). In future studies, more patients will be enrolled to assess the effectiveness of the application, paving the way for the implementation of social training that can also be delivered at home.
The Effect of Cognitive Task Complexity on Healthy Gait in the Walking Corsi Test
Authors: Camp Nicola , Vagnetti Roberto , Bisele Maria , Felton Paul , Hunter Kirsty , Magistro Daniele
Published: June 2023

Dual-task activities are essential within everyday life, requiring visual–spatial memory (VSM) and mobility skills. Navigational memory is an important component of VSM needed to carry out everyday activities, but this is often not included in traditional tests such as the Corsi block tapping test (CBT). The Walking Corsi Test (WalCT) allows both VSM and navigational memory to be tested together, as well as allowing measures of gait to be collected, thus providing a more complete understanding of dual-task function. The aim of this study was to investigate the effect of an increasingly complex cognitive task on gait in a healthy adult population, using the WalCT and body-worn inertial measurement unit (IMU) sensors. Participants completed both the CBT and WalCT, where they were asked to replicate increasingly complex sequences until they were no longer able to carry this out correctly. IMU sensors were worn on the shins throughout the WalCT to assess changes in gait as task complexity increased. Results showed that there were significant differences in several gait parameters between completing a relatively simple cognitive task and completing a complex task. The type of memory used also appeared to have an impact on some gait variables. This indicates that even within a healthy population, gait is affected by cognitive task complexity, which may limit function in everyday dual-task activities.
Relationships among Inflammatory Biomarkers and Self-Reported Treatment-Related Symptoms in Patients Treated with Chemotherapy for Gynecologic Cancer: A Controlled Comparison
Authors: Hoogland Aasha I. , Small Brent J. , Oswald Laura B. , Bryant Crystal , Rodriguez Yvelise , Gonzalez Brian D. , Li Xiaoyin , Janelsins Michelle C. , Bulls Hailey W. , James Brian W. , Arboleda Bianca , Colon-Echevarria Claudia , Townsend Mary K. , Tworoger Shelley S. , Rodriguez Paulo C. , Bower Julienne E. , Apte Sachin M. , Wenham Robert M. , Jim Heather S. L.
Published: June 2023

Previous research suggests that inflammation triggers cancer-treatment-related symptoms (i.e., fatigue, depression, and disruptions in sleep and physical activity), but evidence is mixed. This study examined relationships between inflammatory biomarkers and symptoms in patients with gynecologic cancer compared to age-matched women with no cancer history (i.e., controls). Patients (n = 121) completed assessments before chemotherapy cycles 1, 3, and 6, and 6 and 12 months later. Controls (n = 105) completed assessments at similar timepoints. Changes in inflammation and symptomatology were evaluated using random-effects mixed models, and cross-sectional differences between patients and controls in inflammatory biomarkers and symptoms were evaluated using least squares means. Associations among inflammatory biomarkers and symptoms were evaluated using random-effects fluctuation mixed models. The results indicated that compared to controls, patients typically have higher inflammatory biomarkers (i.e., TNF-alpha, TNFR1, TNFR2, CRP, IL-1ra) and worse fatigue, depression, and sleep (ps < 0.05). Patients reported lower levels of baseline physical activity (p = 0.02) that became more similar to controls over time. Significant associations were observed between CRP, depression, and physical activity (ps < 0.05), but not between inflammation and other symptoms. The results suggest that inflammation may not play a significant role in fatigue or sleep disturbance among gynecologic cancer patients but may contribute to depression and physical inactivity.
MET Receptor Tyrosine Kinase Inhibition Reduces Interferon-Gamma (IFN-γ)-Stimulated PD-L1 Expression through the STAT3 Pathway in Melanoma Cells
Authors: Song Kyu Young , Han Yong Hwan , Roehrich Heidi , Brown Mary E. , Torres-Cabala Carlos , Giubellino Alessio
Published: June 2023

Melanoma is the leading cause of death from cutaneous malignancy. While targeted therapy and immunotherapy with checkpoint inhibitors have significantly decreased the mortality rate of this disease, advanced melanoma remains a therapeutic challenge. Here, we confirmed that interferon-gamma (IFN-γ)-induced PD-L1 expression in melanoma cell lines. This increased expression was down-regulated by the reduction in phosphorylated STAT3 signaling via MET tyrosine kinase inhibitor treatment. Furthermore, immunoprecipitation and confocal immunofluorescence microscopy analysis reveals MET and PD-L1 protein–protein interaction and colocalization on the cell surface membrane of melanoma cells. Together, these findings demonstrate that the IFN-γ-induced PD-L1 expression in melanoma cells is negatively regulated by MET inhibition through the JAK/STAT3 signaling pathway and establish the colocalization and interaction between an RTK and a checkpoint protein in melanoma cells.
Targeting Metabolic Vulnerabilities in Epstein–Barr Virus-Driven Proliferative Diseases
Authors: Leung Nicole Yong Ting , Wang Liang Wei
Published: June 2023

The metabolism of cancer cells and Epstein–Barr virus (EBV) infected cells have remarkable similarities. Cancer cells frequently reprogram metabolic pathways to augment their ability to support abnormal rates of proliferation and promote intra-organismal spread through metastatic invasion. On the other hand, EBV is also capable of manipulating host cell metabolism to enable sustained growth and division during latency as well as intra- and inter-individual transmission during lytic replication. It comes as no surprise that EBV, the first oncogenic virus to be described in humans, is a key driver for a significant fraction of human malignancies in the world (~1% of all cancers), both in terms of new diagnoses and attributable deaths each year. Understanding the contributions of metabolic pathways that underpin transformation and virus replication will be important for delineating new therapeutic targets and designing nutritional interventions to reduce disease burden. In this review, we summarise research hitherto conducted on the means and impact of various metabolic changes induced by EBV and discuss existing and potential treatment options targeting metabolic vulnerabilities in EBV-associated diseases.
Late Effects of Chronic Low Dose Rate Total Body Irradiation on the Heart Proteome of ApoE−/− Mice Resemble Premature Cardiac Ageing
Authors: Azimzadeh Omid , Merl-Pham Juliane , Subramanian Vikram , Oleksenko Kateryna , Krumm Franziska , Mancuso Mariateresa , Pasquali Emanuela , Tanaka Ignacia B. , Tanaka Satoshi , Atkinson Michael J. , Tapio Soile , Moertl Simone
Published: June 2023

Recent epidemiologic studies support an association between chronic low-dose radiation exposure and the development of cardiovascular disease (CVD). The molecular mechanisms underlying the adverse effect of chronic low dose exposure are not fully understood. To address this issue, we have investigated changes in the heart proteome of ApoE deficient (ApoE−/−) C57Bl/6 female mice chronically irradiated for 300 days at a very low dose rate (1 mGy/day) or at a low dose rate (20 mGy/day), resulting in cumulative whole-body doses of 0.3 Gy or 6.0 Gy, respectively. The heart proteomes were compared to those of age-matched sham-irradiated ApoE−/− mice using label-free quantitative proteomics. Radiation-induced proteome changes were further validated using immunoblotting, enzyme activity assays, immunohistochemistry or targeted transcriptomics. The analyses showed persistent alterations in the cardiac proteome at both dose rates; however, the effect was more pronounced following higher dose rates. The altered proteins were involved in cardiac energy metabolism, ECM remodelling, oxidative stress, and ageing signalling pathways. The changes in PPARα, SIRT, AMPK, and mTOR signalling pathways were found at both dose rates and in a dose-dependent manner, whereas more changes in glycolysis and ECM remodelling were detected at the lower dose rate. These data provide strong evidence for the possible risk of cardiac injury following chronic low dose irradiation and show that several affected pathways following chronic irradiation overlap with those of ageing-associated heart pathology.
Multi-Omic Biomarkers Improve Indeterminate Pulmonary Nodule Malignancy Risk Assessment
Authors: Lastwika Kristin J. , Wu Wei , Zhang Yuzheng , Ma Ningxin , Zečević Mladen , Pipavath Sudhakar N. J. , Randolph Timothy W. , Houghton A. McGarry , Nair Viswam S. , Lampe Paul D. , Kinahan Paul E.
Published: June 2023

The clinical management of patients with indeterminate pulmonary nodules is associated with unintended harm to patients and better methods are required to more precisely quantify lung cancer risk in this group. Here, we combine multiple noninvasive approaches to more accurately identify lung cancer in indeterminate pulmonary nodules. We analyzed 94 quantitative radiomic imaging features and 41 qualitative semantic imaging variables with molecular biomarkers from blood derived from an antibody-based microarray platform that determines protein, cancer-specific glycan, and autoantibody–antigen complex content with high sensitivity. From these datasets, we created a PSR (plasma, semantic, radiomic) risk prediction model comprising nine blood-based and imaging biomarkers with an area under the receiver operating curve (AUROC) of 0.964 that when tested in a second, independent cohort yielded an AUROC of 0.846. Incorporating known clinical risk factors (age, gender, and smoking pack years) for lung cancer into the PSR model improved the AUROC to 0.897 in the second cohort and was more accurate than a well-characterized clinical risk prediction model (AUROC = 0.802). Our findings support the use of a multi-omics approach to guide the clinical management of indeterminate pulmonary nodules.
State-of-the-Art and Upcoming Innovations in Pancreatic Cancer Care: A Step Forward to Precision Medicine
Authors: Schepis Tommaso , De Lucia Sara Sofia , Pellegrino Antonio , del Gaudio Angelo , Maresca Rossella , Coppola Gaetano , Chiappetta Michele Francesco , Gasbarrini Antonio , Franceschi Francesco , Candelli Marcello , Nista Enrico Celestino
Published: June 2023

Pancreatic cancer remains a social and medical burden despite the tremendous advances that medicine has made in the last two decades. The incidence of pancreatic cancer is increasing, and it continues to be associated with high mortality and morbidity rates. The difficulty of early diagnosis (the lack of specific symptoms and biomarkers at early stages), the aggressiveness of the disease, and its resistance to systemic therapies are the main factors for the poor prognosis of pancreatic cancer. The only curative treatment for pancreatic cancer is surgery, but the vast majority of patients with pancreatic cancer have advanced disease at the time of diagnosis. Pancreatic surgery is among the most challenging surgical procedures, but recent improvements in surgical techniques, careful patient selection, and the availability of minimally invasive techniques (e.g., robotic surgery) have dramatically reduced the morbidity and mortality associated with pancreatic surgery. Patients who are not candidates for surgery may benefit from locoregional and systemic therapy. In some cases (e.g., patients for whom marginal resection is feasible), systemic therapy may be considered a bridge to surgery to allow downstaging of the cancer; in other cases (e.g., metastatic disease), systemic therapy is considered the standard approach with the goal of prolonging patient survival. The complexity of patients with pancreatic cancer requires a personalized and multidisciplinary approach to choose the best treatment for each clinical situation. The aim of this article is to provide a literature review of the available treatments for the different stages of pancreatic cancer.
Development and Disorders of the Airway in Bronchopulmonary Dysplasia
Authors: Bush Douglas , Juliano Courtney , Bowler Selina , Tiozzo Caterina
Published: June 2023

Bronchopulmonary dysplasia (BPD), a disorder characterized by arrested lung development, is a frequent cause of morbidity and mortality in premature infants. Parenchymal lung changes in BPD are relatively well-characterized and highly studied; however, there has been less emphasis placed on the role that airways disease plays in the pathophysiology of BPD. In preterm infants born between 22 and 32 weeks gestation, the conducting airways are fully formed but still immature and therefore susceptible to injury and further disruption of development. The arrest of maturation results in more compliant airways that are more susceptible to deformation and damage. Consequently, neonates with BPD are prone to developing airway pathology, particularly for patients who require intubation and positive-pressure ventilation. Airway pathology, which can be divided into large and small airways disease, results in increased respiratory morbidity in neonates with chronic lung disease of prematurity.
Experiences of Hearing Parents of Children with Hearing Loss: A Qualitative Study
Authors: Dikeç Gül , Türk Eda , Yüksel Esin , Çelebi Kübra , Özdemir Meltem
Published: June 2023

This qualitative study was carried out with a phenomenological design to determine the life experiences of the parents of children with hearing loss. The study sample consisted of twenty parents, who did not have hearing loss, of children with hearing loss registered in a special education and rehabilitation center. The data were collected through in-depth interviews in Istanbul between December and January 2022. Colaizzi’s phenomenological interpretation method was used for qualitative data analysis. It was determined that parents of children with hearing loss experienced anxiety, sadness, and happiness during diagnosis. They needed more information at first, but then they gained knowledge in the process, and it took work to accept this process. They stated that having a child with hearing loss requires more time, responsibility, and effort than other children. This situation affects their social life, and they experience interpersonal conflicts. When parents were asked how they coped, they said they did it through prayer, social support, or time to themselves. It can be recommended to apply psychosocial intervention programs to the parents of children with hearing loss, especially their mothers, from the first diagnosis process.
Parental Burnout in the Context of Special Needs, Adoption, and Single Parenthood
Authors: Roskam Isabelle , Mikolajczak Moïra
Published: June 2023

Although early work on parental burnout in the 1980s did not link parental burnout to specific parenting situations, the idea that parents affected by specific vulnerability factors were particularly at risk of burnout quickly emerged. Based on the etiological model of parental burnout (i.e., the balance between risks and resources), the objective of this study was to investigate if there were specific vulnerability factors that significantly increase the risk of parental burnout. 2563 parents participated in the study. We compared parents with a child with special needs (n = 25), parents who had adopted a child (n = 130), and single parents (n = 109), to strictly matched control groups of parents. Parents with a child with special needs displayed higher burnout and lower balance between risk and resources than the control group; parents with an adopted child had similar levels of both parental burnout and balance; and single parents had higher parental burnout but similar balance. Parents who combined specific several vulnerability factors were at greater risk of burnout. Single parenthood and adoption do not in themselves trigger a process leading de facto to other risk factors, but having a child with special needs does.
The Future of Newborn Genomic Testing
Authors: Lantos John D.
Published: June 2023

Genome sequencing (GS) provides exciting opportunities to rapidly identify a diagnosis in critically ill newborns and children with rare genetic conditions. Nevertheless, there are reasons to remain cautious about the use of GS. Studies to date have been mostly in highly selected populations of babies with unusual clinical presentations. GS leads to diagnoses in many such infants. More rarely, it leads to beneficial changes in management. Parents and physicians whose babies meet these criteria and for whom GS is performed both find these results useful. The concern is this: we do not know how useful such testing will be in the general population. We can speculate that a number of problems will arise as the use of GS expands. First, the percentage of cases in which a valid molecular diagnosis is made will likely go down. The number of ambiguous results or false positives will rise. Genetic counseling will become more complex and challenging. We do not know the relative cost-effectiveness of whole genome, whole exome, or targeted panels in different populations. We do not know the relative contribution of a molecular diagnosis to the decision to withdraw life support. We will have to carefully evaluate the use of such testing in order to understand whether it truly improves outcome and survival or reduces symptoms in babies who are tested. Each of these concerns will require careful study of both the technology and the ethical issues to allow us to harness the potential of these new technologies while avoiding foreseeable problems. Studies are underway to see how the tests are used in general populations. These studies should generate important information to guide clinicians and policymakers. As part of informed consent, doctors should explain to parents that genetic results are not always straightforward. Sometimes, they confirm a diagnosis that was already suspected. Sometimes, they rule out a possible diagnosis. Sometimes, the results are ambiguous and difficult to interpret. Anticipatory discussions should try to give parents a realistic understanding of the likely impact of a genetic diagnosis. Diagnostic genomic testing for newborns is a science that is still in its infancy. More research is essential in order to establish how to personalize this promising but sometimes problematic tool.
Association of Atherogenic Index of Plasma with Cardiometabolic Risk Factors and Markers in Lean 14-to-20-Year-Old Individuals: A Cross-Sectional Study
Authors: Šebeková Katarína , Gurecká Radana , Csongová Melinda , Koborová Ivana , Celec Peter
Published: June 2023

Cardiometabolic risk factors at a young age pose a significant risk for developing atherosclerotic cardiovascular disease in adulthood. Atherogenic dyslipidemia is highly associated with obesity and metabolic syndrome already in young age. It remains unclear whether cardiometabolic risk factors associate with the atherogenic index of plasma (AIP = log (TAG/HDL-C) in lean subjects with low atherogenic risk. As both the AIP and markers of cardiometabolic risk are continuous variables, we expected their association to be linear before the manifestation of obesity and atherogenic dyslipidemia. We analyzed the prevalence of increased atherogenic risk (AIP ≥ 0.11) in 2012 lean 14-to-20-year-old subjects (55% females) and the trends of cardiometabolic risk factors across the quartiles (Q) of AIP in a subgroup of 1947 (56% females) subjects with low atherogenic risk (AIP < 0.11). The prevalence of AIP ≥ 0.11 reached 3.6% in females and 8.5% in males. HDL-C, non-HDL-C, triglycerides, and the continuous metabolic syndrome score showed a stepwise worsening across the AIP quartiles in both sexes. Measures of obesity and insulin resistance were worse in Q4 vs. Q1 groups, and leukocyte counts were higher in Q4 and Q3 vs. Q1. Females in Q4 presented with a higher C-reactive protein and lower adiponectin, estradiol, and testosterone levels. The multivariate regression model selected non-HDL-C, QUICKI, and erythrocyte counts as significant predictors of AIP in males; and non-HDL-C and C-reactive protein in females. A question arises whether the lean individuals on the upper edge of low atherogenic risk are prone to earlier manifestation of metabolic syndrome and shift to the higher AIP risk group.
Socio-Emotional Experiences and Wellbeing of Deaf and Hard of Hearing Children and Their Parents before and during the COVID-19 Pandemic
Authors: Gillespie Alanna N. , Smith Libby , Shepherd Daisy A. , Xu Jessica , Khanal Rija , Sung Valerie
Published: June 2023

Deaf and hard of hearing (DHH) children in Victoria, Australia, were exposed to strict public health restrictions, including sustained lockdowns, during the COVID-19 pandemic. DHH children have higher health and socio-emotional needs than their hearing peers. We aimed to (1) describe the socio-emotional experiences of DHH children and their parents and (2) compare child and parent socio-emotional wellbeing, before and during the COVID-19 pandemic. Between May and September 2020, 497 (62%) parents of DHH children from the Victorian Childhood Hearing Longitudinal Databank completed an online survey. Measures were drawn from the CoRonavIruS Health Impact Survey (CRISIS) v3.0. Data were summarized using descriptive statistics to compare outcomes before and during the pandemic. Parents reported their children to have more negative socio-emotional wellbeing (mean emotions/worries score, EWS, changed from 0.76 pre-pandemic to 1.10 during the pandemic, mean difference 0.34, 95% CI: 0.28 to 0.39), regardless of the type or severity of hearing loss. Parents also had more negative socio-emotional wellbeing (mean EWS changed from 1.05 pre-pandemic to 1.43 during the pandemic, mean difference 0.38, 95% CI: 0.31 to 0.44). Negative socio-emotional experiences co-occurred with large social changes during the pandemic. Additional services should support the socio-emotional wellbeing of DHH children during significant adverse childhood experiences.