bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling Electric Fields in Transcutaneous Spinal Direct Current Stimulation: A Clinical Perspective
Authors: Guidetti Matteo , Giannoni-Luza Stefano , Bocci Tommaso , Pacheco-Barrios Kevin , Bianchi Anna Maria , Parazzini Marta , Ionta Silvio , Ferrucci Roberta , Maiorana Natale Vincenzo , Verde Federico , Ticozzi Nicola , Silani Vincenzo , Priori Alberto
Published: April 2023

Clinical findings suggest that transcutaneous spinal direct current stimulation (tsDCS) can modulate ascending sensitive, descending corticospinal, and segmental pathways in the spinal cord (SC). However, several aspects of the stimulation have not been completely understood, and realistic computational models based on MRI are the gold standard to predict the interaction between tsDCS-induced electric fields and anatomy. Here, we review the electric fields distribution in the SC during tsDCS as predicted by MRI-based realistic models, compare such knowledge with clinical findings, and define the role of computational knowledge in optimizing tsDCS protocols. tsDCS-induced electric fields are predicted to be safe and induce both transient and neuroplastic changes. This could support the possibility to explore new clinical applications, such as spinal cord injury. For the most applied protocol (2–3 mA for 20–30 min, active electrode over T10–T12 and the reference on the right shoulder), similar electric field intensities are generated in both ventral and dorsal horns of the SC at the same height. This was confirmed by human studies, in which both motor and sensitive effects were found. Lastly, electric fields are strongly dependent on anatomy and electrodes’ placement. Regardless of the montage, inter-individual hotspots of higher values of electric fields were predicted, which could change when the subjects move from a position to another (e.g., from the supine to the lateral position). These characteristics underlines the need for individualized and patient-tailored MRI-based computational models to optimize the stimulation protocol. A detailed modeling approach of the electric field distribution might contribute to optimizing stimulation protocols, tailoring electrodes’ configuration, intensities, and duration to the clinical outcome.
Microbiological and Cytokine Profiling of Menstrual Blood for the Assessment of Endometrial Receptivity: A Pilot Study
Authors: Jain Mark , Mladova Elena , Shichanina Anna , Kirillova Karina , Povarova Anna , Scherbakova Liya , Samokhodskaya Larisa , Panina Olga
Published: April 2023

Endometrial receptivity (ER) is a key factor required for the successful implantation of the embryo. However, the evaluation of ER is challenging, as a nondisruptive sampling of endometrial biomaterial by conventional methods is only possible outside of the embryo transfer (ET) cycle. We propose a novel approach for the assessment of ER—microbiological and cytokine profiling of menstrual blood aspirated directly from the uterine cavity at the beginning of the cryo-ET cycle. The aim of the pilot study was to evaluate its prognostic potential regarding the outcome of the in vitro fertilization procedure. Samples collected from a cohort of 42 patients undergoing cryo-ET were analyzed by a multiplex immunoassay (48 various cytokines, chemokines, and growth factors) and a real-time PCR assay (28 relevant microbial taxa and 3 members of the Herpesviridae family). Significant differences between groups of patients who achieved and did not achieve pregnancy were observed for G-CSF, GRO-α, IL-6, IL-9, MCP-1, M-CSF, SDF-1α, TNF-β, TRAIL, SCF, IP-10, and MIG (p < 0.05), whereas microbial profiles were not associated with the outcome of cryo-ET. It appeared that levels of IP-10 and SCGF-β were significantly lower (p < 0.05), in patients with endometriosis. Menstrual blood may provide great opportunities to noninvasively investigate various parameters of the endometrium.
Is Cataract in Patients under 60 Years Associated with Oxidative Stress?
Authors: Lesiewska Hanna , Woźniak Alina , Reisner Paweł , Czosnyka Krzysztof , Stachura Joanna , Malukiewicz Grażyna
Published: April 2023

Oxidative stress is considered as a possible factor in the genesis of cataract. The study aimed to determine the systemic antioxidant status in cataract patients under 60 years. We studied 28 consecutive cataract patients, mean of 53 years (SD = 9.2), a range of 22–60 and 37 controls. In erythrocytes, activity of antioxidant enzymes was determined: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), in contrast with plasma concentrations of vitamin A and E. Conjugated dienes (CD) level and protein carbonyls (PC) concentration were also determined in plasma. Malondialdehyde (MDA) concentrations in erythrocytes and plasma were also measured. SOD and GPx activity and vitamin A and E concentrations were lower in cataract patients (p = 0.000511, 0.02, 0.022, and 0.000006, respectively). MDA plasma and erythrocytes concentrations were higher in cataract patients (p = 0.000001 and 0.0000001, respectively). PC concentration was higher in cataract patients than in controls (p = 0.00000013). There were statistically significant correlations between oxidative stress markers both in the cataract patients group as well as in the control group. Cataract incidence in patients under 60 years seems to be accompanied by enhanced lipid peroxidation and protein oxidation, as well as antioxidant defense depletion. Thus, supplementation with antioxidants could be beneficial in this group of patients.
The Effects of Alcohol Intoxication and Withdrawal on Hypothalamic Neurohormones and Extrahypothalamic Neurotransmitters
Authors: Simon Balázs , Buzás András , Bokor Péter , Csabafi Krisztina , Ibos Katalin Eszter , Bodnár Éva , Török László , Földesi Imre , Siska Andrea , Bagosi Zsolt
Published: April 2023

The aim of the present study was to determine the effects of alcohol intoxication and withdrawal on hypothalamic neurohormones such as corticotropin-releasing factor (CRF) and arginine vasopressin (AVP), and extrahypothalamic neurotransmitters such as striatal dopamine (DA), amygdalar gamma aminobutyric acid (GABA), and hippocampal glutamate (GLU). In addition, the participation of the two CRF receptors, CRF1 and CRF2, was investigated. For this purpose, male Wistar rats were exposed to repeated intraperitoneal (ip) administration of alcohol every 12 h, for 4 days and then for 1 day of alcohol abstinence. On the fifth or sixth day, intracerebroventricular (icv) administration of selective CRF1 antagonist antalarmin or selective CRF2 antagonist astressin2B was performed. After 30 min, the expression and concentration of hypothalamic CRF and AVP, the concentration of plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT), and the release of striatal DA, amygdalar GABA, and hippocampal GLU were measured. Our results indicate that the neuroendocrine changes induced by alcohol intoxication and withdrawal are mediated by CRF1, not CRF2, except for the changes in hypothalamic AVP, which are not mediated by CRF receptors.
Dissecting the Molecular Role of ADIPOQ SNPs in Saudi Women Diagnosed with Gestational Diabetes Mellitus
Authors: Alshammary Amal F. , Ansar Sabah , Farzan Raed , Alsobaie Sarah F. , Alageel Arwa A. , Al-Hakeem Malak Mohammed , Ali Khan Imran
Published: April 2023

The traditional definition of gestational diabetes mellitus (GDM) is the leading cause of carbohydrate intolerance in hyperglycemia of varying severity, with onset or initial detection during pregnancy. Previous studies have reported a relationship among obesity, adiponectin (ADIPOQ), and diabetes in Saudi Arabia. ADIPOQ is an adipokine that is produced and secreted by adipose tissue involved in the regulation of carbohydrate and fatty acid metabolism. This study investigated the molecular association between rs1501299, rs17846866, and rs2241766 single-nucleotide polymorphisms (SNPs) in ADIPOQ and GDM in Saudi Arabia. Patients with GDM and control patients were selected, and serum and molecular analyses were performed. Statistical analyses were performed on clinical data, Hardy Weinberg Equilibrium, genotype and allele frequencies, multiple logistic regression, ANOVA, haplotype, linkage disequilibrium, as well as MDR and GMDR analyses. The clinical data showed significant differences in various parameters between the GDM and non-GDM groups (p < 0.05). In GDM women with alleles, genotypes, and different genetic models, the rs1501299 and rs2241766 SNPs showed a strong association (p < 0.05). Multiple logistic regression analysis revealed a negative correlation (p > 0.05). This study concluded that rs1501299 and rs2241766 SNPs were strongly associated with GDM in women in Saudi Arabia.
The Role of Adipokines in Health and Disease
Authors: Clemente-Suárez Vicente Javier , Redondo-Flórez Laura , Beltrán-Velasco Ana Isabel , Martín-Rodríguez Alexandra , Martínez-Guardado Ismael , Navarro-Jiménez Eduardo , Laborde-Cárdenas Carmen Cecilia , Tornero-Aguilera José Francisco
Published: April 2023

Adipokines are cell-signaling proteins secreted by adipose tissue that has been related to a low-grade state of inflammation and different pathologies. The present review aims to analyze the role of adipokines in health and disease in order to understand the important functions and effects of these cytokines. For this aim, the present review delves into the type of adipocytes and the cytokines produced, as well as their functions; the relations of adipokines in inflammation and different diseases such as cardiovascular, atherosclerosis, mental diseases, metabolic disorders, cancer, and eating behaviors; and finally, the role of microbiota, nutrition, and physical activity in adipokines is discussed. This information would allow for a better understanding of these important cytokines and their effects on body organisms.
Progress in Nano-Biosensors for Non-Invasive Monitoring of Stem Cell Differentiation
Authors: Kang Min-Ji , Cho Yeon-Woo , Kim Tae-Hyung
Published: April 2023

Non-invasive, non-destructive, and label-free sensing techniques are required to monitor real-time stem cell differentiation. However, conventional analysis methods, such as immunocytochemistry, polymerase chain reaction, and Western blot, involve invasive processes and are complicated and time-consuming. Unlike traditional cellular sensing methods, electrochemical and optical sensing techniques allow non-invasive qualitative identification of cellular phenotypes and quantitative analysis of stem cell differentiation. In addition, various nano- and micromaterials with cell-friendly properties can greatly improve the performance of existing sensors. This review focuses on nano- and micromaterials that have been reported to improve sensing capabilities, including sensitivity and selectivity, of biosensors towards target analytes associated with specific stem cell differentiation. The information presented aims to motivate further research into nano-and micromaterials with advantageous properties for developing or improving existing nano-biosensors to achieve the practical evaluation of stem cell differentiation and efficient stem cell-based therapies.
Label-Free Sequence-Specific Visualization of LAMP Amplified Salmonella via DNA Machine Produces G-Quadruplex DNAzyme
Authors: Zeng Huan , Huang Shuqin , Chen Yunong , Chen Minshi , He Kaiyu , Fu Caili , Wang Qiang , Zhang Fang , Wang Liu , Xu Xiahong
Published: April 2023

Salmonella is one of four key global causes of diarrhea, and in humans, it is generally contracted through the consumption of contaminated food. It is necessary to develop an accurate, simple, and rapid method to monitor Salmonella in the early phase. Herein, we developed a sequence-specific visualization method based on loop-mediated isothermal amplification (LAMP) for the detection of Salmonella in milk. With restriction endonuclease and nicking endonuclease, amplicons were produced into single-stranded triggers, which further promoted the generation of a G-quadruplex by a DNA machine. The G-quadruplex DNAzyme possesses peroxidase-like activity and catalyzes the color development of 2,2′-azino-di-(3-ethylbenzthiazoline sulfonic acid) (ABTS) as the readouts. The feasibility for real samples analysis was also confirmed with Salmonella spiked milk, and the sensitivity was 800 CFU/mL when observed with the naked eye. Using this method, the detection of Salmonella in milk can be completed within 1.5 h. Without the involvement of any sophisticated instrument, this specific colorimetric method can be a useful tool in resource-limited areas.
The Role of Cohesion and Productivity Norms in Performance and Social Effectiveness of Work Groups and Informal Subgroups
Authors: Sidorenkov Andrey V. , Borokhovski Evgueni F.
Published: April 2023

The study addresses the direct and indirect relationship of group cohesion and productivity norm with the perceived performance effectiveness (plan and current tasks implementation and performance success in challenging conditions) and social effectiveness (satisfaction with the group/subgroup and psychological comfort in the group/subgroup) at the levels of work groups and informal subgroups. Thirty-nine work groups from fifteen Russian organizations of different activity profiles, namely services, trade, and manufacturing, took part in the study. The vast majority of them were characterized by relatively low task interdependence. Within the work groups, informal subgroups (from one to three per group) were identified. The cohesion of groups and subgroups was positively and significantly stronger associated with their social effectiveness than with performance effectiveness. The cohesion of subgroups was also indirectly related to social effectiveness of the work groups, i.e., this association was mediated by the subgroup social effectiveness. The index of productivity norm was positively related to perceived performance effectiveness only at the subgroup level, but not at the group level. The productivity norm of the subgroups was also indirectly related to the perceived performance effectiveness of the groups, i.e., this association was mediated by the subgroup performance effectiveness. The indirect relationship between subgroup productivity norm and group performance effectiveness was more complex when cohesion within subgroups was taken into account.
The Association of Caregivers’ Socio-Economic Conditions with Family Caregiving Norms: Evidence from China
Authors: Kuramoto Yu , Nabeshima Honoka , Khan Mostafa Saidur Rahim , Kadoya Yoshihiko
Published: April 2023

Similar to her neighboring country, Japan, China faces significant difficulties in providing long-term care to the elderly. Female household members who traditionally provided necessary caregiving are no longer available as much as in the past due to the demographic and socioeconomic changes over the past few decades. Against this backdrop, we investigated how socioeconomic factors affect the perception of family caregiving norms in China, using an international comparative household dataset that allowed us to compare China with Japan, the latter being extensively investigated. We used ordered probit regression to estimate the model equation. Our results show that rural residency, household assets, and government dependency are positively associated with the perception of care. A notable difference from the Japanese results is that rural residents have a rather positive perception of family caregiving norms. Furthermore, urban–rural subsample analyses revealed that women in rural areas perceive caregiving negatively.
Cumulative Risk and Externalizing Behaviors during Infancy in a Predominantly Latine Sample
Authors: Rowe Greighson M. , Bagner Daniel M. , Lorenzo Nicole E.
Published: April 2023

Externalizing behavior problems are among the top mental health concerns in early childhood, and many parenting interventions have been developed to address this issue. To better understand predictors of parenting intervention outcomes in high-risk families, this secondary data analysis evaluated the moderating effect of cumulative risk on child externalizing behaviors, parenting skills, and intervention dropout after completion of a home-based adaptation of the child-directed interaction phase of parent–child interaction therapy (PCIT) called the Infant Behavior Program (IBP). The participants included 58 toddlers (53% male; average age of 13.5 months; and 95% Hispanic or Latine) who were part of a larger randomized control trial in which families were randomly assigned to receive the IBP or treatment as usual (TAU). Cumulative risk was found to moderate the effect of the intervention group on child externalizing behaviors such that the participants in the intervention group with higher cumulative risk scores had greater reductions in externalizing behaviors. A potential explanation for these unexpected findings may be that the obstacles to treatment that were previously imposed by comorbid risk factors (i.e., lack of transportation, time commitment, and language barriers) were adequately addressed such that the families who most needed the intervention were able to remain fully engaged.
Factors That Impact the Relationship between Perceived Organizational Support and Technostress in Teachers
Authors: Solís Patricia , Lago-Urbano Rocío , Real Castelao Sara
Published: April 2023

In the last two years, the obligatory use of technologies due to the COVID-19 pandemic has increased the technostress suffered by education professionals. This study investigates the relationships between technostress and perceived organizational support and the influence of certain socio-demographic variables. An online survey was administered to 771 teachers working in different educational stages in various autonomous communities in Spain. Perceived organizational support was found to be significantly correlated with technostress. Women tend to experience more technostress in general and significant gender differences were also found in the dimension of anxiety. The analyzed data also suggest that perceived organizational support is higher in private schools. In urban centers, teachers’ technostress increases in higher educational stages, such as secondary education and baccalaureate. Further work is needed to develop school policies that address the needs of teachers and provide support for those at risk of technostress. In addition, there is a need to design coping strategies and prioritize the most at-risk sectors to improve their overall health and well-being.
Effect of Using Glass Fiber Reinforced Polymer (GFRP) and Deformed Steel Bars on the Bonding Behavior of Lightweight Foamed Concrete
Authors: Abd Suhad M. , Hadi Rafal , Abdal Shaker , Shamim Saba , Najm Hadee Mohammed , Sabri Mohanad Muayad Sabri
Published: April 2023

The study aims to conduct a direct pull-out test on fifty-four cube specimens considering different variables, including the type of reinforcement (sand-coated glass fiber-reinforced polymer (GFRP) and ribbed steel bars); the type of concrete (normal weight concrete NWC and lightweight foamed concrete LWFC); the diameter of the reinforcing bars (10 mm; 12 mm; and 16 mm) and the bonded length (3∅, 4∅, and 5∅). The hybrid fiber hooked-end steel (0.4% by volume) and polypropylene (0.2% by volume), respectively were used to improve the properties of LWFC by converting the brittle failure to ductile. The results showed that in the case of strengthened foamed concrete (FC), the bond strength with steel bars was greater compared to that with the GFRP bars. The bond strength ratio between the GFRP and steel bars of the FC specimens was found to vary between 37.8–89.3%. Additionally, in all specimens of FC, pull-out failure was witnessed with narrower crack width compared to NWC. Furthermore, mathematical equations have been proposed for predicting the bond strength of FC with steel and GFRP bars and showed good correlation with the experimental results.
Dynamic Mechanical Strength Prediction of BFRC Based on Stacking Ensemble Learning and Genetic Algorithm Optimization
Authors: Zheng Jiayan , Wang Minghui , Yao Tianchen , Tang Yichen , Liu Haijing
Published: April 2023

Split Hopkinson pressure bar (SHPB) tests are usually used to determine the dynamic mechanical strength of basalt-fiber-reinforced concrete (BFRC), but this test method is time-consuming and expensive. This paper makes predictions about the dynamic mechanical strength of BFRC by employing machine learning (ML) algorithms and feature sets drawn from experimental data from prior works. However, there is still the problem of improving the accuracy of the dynamic mechanical strength prediction by the BFRC, which remains a challenge. Using stacking ensemble learning and genetic algorithms (GA) to optimize parameters, this study proposes a prediction method that combines these two techniques for obtaining accurate predictions. This method is composed of three parts: (1) the training uses multiple base learners, and the algorithms employed by the learners include extreme gradient boosting (XGBoost), gradient boosting (GB), random forest (RF), and support vector regression (SVR); (2) multi-base learners are combined using a stacking strategy to obtain the final prediction; and (3) using GA, the parameters are optimized in the prediction model. An experiment was conducted to compare the proposed approach with popular techniques for machine learning. In the study, the stacking ensemble algorithm integrated the base learner prediction results to improve the model’s performance and the GA further improved prediction accuracy. As a result of the application of the method, the dynamic mechanical strength of BFRC can be predicted with high accuracy. A SHAP analysis was also conducted using the stacking model to determine how important the contributing properties are and the sensitivity of the stacking model. Based on the results of this study, it was found that in the SHPB test, the strain rate had the most significant influence on the DIF, followed by the specimen diameter and the compressive strength.
Applicability of Standard Rheological Evaluation Methods for High Content SBS Polymer Modified Asphalts
Authors: Yao Hongru , Wang Tao , Wang Qiang , Cao Yadong , Zhou Xiaolong
Published: April 2023

High content SBS polymer modified asphalt (HCPMA) can serve as pavements under heavy traffic and a wide range of temperatures. However, the applicability and validity of standard rheological evaluation methods to characterize HCPMA are still unclear. In this study, the influence of SBS content on the conventional properties and rheological behavior of HCPMA was analyzed. A higher content of SBS can improve the performance grade of the asphalt binder to PG100-34. The slope of the Jnr-σ linear curves from the MSCR under various stress levels decreases when the SBS content increases. The slope of the Jnr-σ linear curves can replace Jnrdiff as an indicator of stress sensitivity. A higher content of SBS can also decrease the flexural creep stiffness and increase the creep rate of the binders. The binder fatigue resistance parameter increases and the binder yields at higher strain, with increasing SBS content. These results show that a higher content of SBS can further improve the resistance to rutting, thermal cracking, and fatigue. Current standard rheological methods should be modified when evaluating HCPMA. The results also show that conventional tests are not valid for evaluating the performance of HCPMA.
Impact of Microclimate on People’s Experiences and Behaviours in the Cultural Consumption Space: A Case Study of Panjiayuan Antique Market in Beijing, China
Authors: Han Mo , Han Bing , Liu Siyi , Sun Ziwen
Published: April 2023

Antique and cultural consumption spaces make a great contribution to urban vitality where numerous people walk, stay, and trade. However, how these people’s experiences and behaviours are affected by the microclimate of such spaces has not been studied till now. To address this gap, and using the concept of Post-occupancy Evaluation (POE) as a basis, our study investigated microclimate factors, subjective experiences, and spatiotemporal behaviour patterns in Panjiayuan Antique Market in Beijing, China. Using a mixed-methods approach comprising subjective questionnaires (n = 101), face-to-face interviews (n = 81), spatiotemporal behaviour mapping (n = 8455), and on-site observations, our results showed that microclimates impact people’s experiences and behaviours, with visibility and noise being the two primary impact factors. Most female visitors are more sensitive to the microclimate than male visitors. Furthermore, vendors in the Antique Market preferred to amend their nearby environments to increase the microclimate quality to offer a better experience to visitors around them. This study developed a comprehensive methodology that expands POE in relation to microclimatic factors in the context of cultural consumption spaces. These findings suggest that microclimates have different impacts on people’s experiences and behaviours in different spaces, which should be considered when designing and renewing urban antique markets in the future.
The Role of STATs in Ovarian Cancer: Exploring Their Potential for Therapy
Authors: Standing David , Feess Emma , Kodiyalam Satvik , Kuehn Michael , Hamel Zachary , Johnson Jaimie , Thomas Sufi Mary , Anant Shrikant
Published: April 2023

Ovarian cancer (OvCa) is a deadly gynecologic malignancy that presents many clinical challenges due to late-stage diagnoses and the development of acquired resistance to standard-of-care treatment protocols. There is an increasing body of evidence suggesting that STATs may play a critical role in OvCa progression, resistance, and disease recurrence, and thus we sought to compile a comprehensive review to summarize the current state of knowledge on the topic. We have examined peer reviewed literature to delineate the role of STATs in both cancer cells and cells within the tumor microenvironment. In addition to summarizing the current knowledge of STAT biology in OvCa, we have also examined the capacity of small molecule inhibitor development to target specific STATs and progress toward clinical applications. From our research, the best studied and targeted factors are STAT3 and STAT5, which has resulted in the development of several inhibitors that are under current evaluation in clinical trials. There remain gaps in understanding the role of STAT1, STAT2, STAT4, and STAT6, due to limited reports in the current literature; as such, further studies to establish their implications in OvCa are necessitated. Moreover, due to the deficiency in our understanding of these STATs, selective inhibitors also remain elusive, and therefore present opportunities for discovery.
Learning from Adaptations to the COVID-19 Pandemic: How Teleconsultation Supported Cancer Care Pathways at a Comprehensive Cancer Center in Northern Italy
Authors: Caviola Giada , Daolio Jessica , Pellegri Carlotta , Cigarini Francesca , Braglia Luca , Foracchia Marco , Mazzini Elisa , Cerullo Loredana
Published: April 2023

Multidisciplinary team (MDT) meetings are recognized as the gold standard for care management of cancer patients, and during the COVID-19 pandemic they were considered a priority to be maintained. Due to pandemic-related restrictions, MDT meetings were forcibly converted from in-person to telematic format. This retrospective study evaluated the annual performance of four MDT meeting indicators (MDT members’ attendance, number of discussed cases, frequency of MDT meetings, and duration) between 2019 and 2022 to report on the implementation of teleconsultation in MDT meetings related to 10 cancer care pathways (CCPs). Over the study period, MDT member participation and the number of discussed cases improved or did not change in 90% (9/10) and 80% (8/10) of the CCPs, respectively. We did not observe significant differences in any of the CCPs included in the study regarding the annual frequency and duration of MDT meeting. Considering the rapidity, extent, and intensity with which telematic tools were adopted due to the COVID-19 pandemic, the results of this study showed that MDT teleconsultation supported the CCPs, and consequently, the delivery of cancer care in COVID-19 times, helping to understand the effects of telematic tools on health care performance and the parties involved.
Usefulness of New Neutrophil-Related Hematologic Parameters in Patients with Myelodysplastic Syndrome
Authors: Kwiecień Iwona , Rutkowska Elżbieta , Gawroński Krzysztof , Kulik Katarzyna , Dudzik Alicja , Zakrzewska Agata , Raniszewska Agata , Sawicki Waldemar , Rzepecki Piotr
Published: April 2023

Myelodysplastic syndromes (MDS) are common malignant disorders with a poor prognosis. It is necessary to search for new rapid diagnostic methods to detect MDS patients with cytogenetic changes. The aim of the study was to assess new hematological neutrophil- and monocyte- related parameters I then bone marrow of MDS patient with and without cytogenetic changes. A total of 45 patients with MDS, including 17 patients with cytogenetic changes, were examined. The study was conducted using the Sysmex XN-Series hematological analyzer. New neutrophil and monocyte parameters, such as immature granulocytes (IG), neutrophil reactivity intensity (NEUT-RI), neutrophil granularity intensity (NEUT-GI), neutrophil size (NE-FSC) and neutrophil/monocyte data relating to granularity, activity and volume (NE-WX/MO-WX, NE-WY/MO-WY, NE-WZ/MO-WZ, MO-X, MO-Y, MO-Z) were evaluated. We observed higher median proportions of NE-WX, NE-WY, NE-WZ, and IG counts in MDS patients with cytogenetic changes than in patients without cytogenetic changes. The NE-FSC parameter was lower in MDS patients with cytogenetic changes than in patients without cytogenetic changes. The combination of new neutrophil parameters was found to be a new successful approach in distinguishing MDS patients with cytogenetic changes from patients without cytogenetic changes. It appears that there may be unique neutrophil parameter signatures associated with an underlying mutation.
A Nomogram Incorporating Neutrophil-to-Lymphocyte Ratio and Squamous Cell Carcinoma Antigen Predicts the Prognosis of Oral Cancers
Authors: Tsai Yao-Te , Lai Chia-Hsuan , Chang Geng-He , Hsu Cheng-Ming , Tsai Ming-Shao , Liao Chun-Ta , Kang Chung-Jan , Tsai Yuan-Hsiung , Lee Yi-Chan , Huang Ethan I. , Tsai Ming-Hsien , Fang Ku-Hao
Published: April 2023

We introduced a novel squamous cell carcinoma inflammatory index (SCI) and explored its prognostic utility for individuals with operable oral cavity squamous cell carcinomas (OSCCs). We retrospectively analyzed data from 288 patients who were given a diagnosis of primary OSCC from January 2008 to December 2017. The SCI value was derived by multiplying the serum squamous cell carcinoma antigen and neutrophil-to-lymphocyte ratio values. We appraised the associations of the SCI with survival outcomes by performing Cox proportional hazards and Kaplan–Meier analyses. We constructed a nomogram for survival predictions by incorporating independent prognostic factors in a multivariable analysis. By executing a receiver operating characteristic curve analysis, we identified the SCI cutoff to be 3.45, and 188 and 100 patients had SCI values of <3.45 and ≥3.45, respectively. The patients with a high SCI (≥3.45) were associated with worse disease-free survival and overall survival than those with a low SCI (<3.45). An elevated preoperative SCI (≥3.45) predicted adverse overall survival (hazard ratio [HR] = 2.378; p < 0.002) and disease-free survival (HR = 2.219; p < 0.001). The SCI-based nomogram accurately predicted overall survival (concordance index: 0.779). Our findings indicate that SCI is a valuable biomarker that is highly associated with patient survival outcomes in OSCC.
18F-FDG PET/CT Maximum Tumor Dissemination (Dmax) in Lymphoma: A New Prognostic Factor?
Authors: Albano Domenico , Treglia Giorgio , Dondi Francesco , Calabrò Anna , Rizzo Alessio , Annunziata Salvatore , Guerra Luca , Morbelli Silvia , Tucci Alessandra , Bertagna Francesco
Published: April 2023

Recently, several studies introduced the potential prognostic usefulness of maximum tumor dissemination (Dmax) measured by 2-deoxy-2-fluorine-18-fluoro-D-glucose positron-emission tomography/computed tomography (18F-FDG PET/CT). Dmax is a simple three-dimensional feature that represents the maximal distance between the two farthest hypermetabolic PET lesions. A comprehensive computer literature search of PubMed/MEDLINE, Embase, and Cochrane libraries was conducted, including articles indexed up to 28 February 2023. Ultimately, 19 studies analyzing the value of 18F-FDG PET/CT Dmax in patients with lymphomas were included. Despite their heterogeneity, most studies showed a significant prognostic role of Dmax in predicting progression-free survival (PFS) and overall survival (OS). Some articles showed that the combination of Dmax with other metabolic features, such as MTV and interim PET response, proved to better stratify the risk of relapse or death. However, some methodological open questions need to be clarified before introducing Dmax into clinical practice.
Current Perioperative Care in Pancreatoduodenectomy: A Step-by-Step Surgical Roadmap from First Visit to Discharge
Authors: Giuliani Tommaso , Perri Giampaolo , Kang Ravinder , Marchegiani Giovanni
Published: April 2023

Pancreaticoduodenectomy (PD) is a mainstay in the management of periampullary tumors. Treatment algorithms increasingly employ a multimodal strategy, which includes neoadjuvant and adjuvant therapies. However, the successful treatment of a patient is contingent on the execution of a complex operation, whereby minimizing postoperative complications and optimizing a fast and complete recovery are crucial to the overall success. In this setting, risk reduction and benchmarking the quality of care are essential frameworks through which modern perioperative PD care must be delivered. The postoperative course is primarily influenced by pancreatic fistulas, but other patient- and hospital-associated factors, such as frailty and the ability to rescue from complications, also affect the outcomes. A comprehensive understanding of the factors influencing surgical outcomes allows the clinician to risk stratify the patient, thereby facilitating a frank discussion of the morbidity and mortality of PD. Further, such an understanding allows the clinician to practice based on the most up-to-date evidence. This review intends to provide clinicians with a roadmap to the perioperative PD pathway. We review key considerations in the pre-, intra-, and post-operative periods.
A Comprehensive Narrative Review on the History, Current Landscape, and Future Directions of Hepatocellular Carcinoma (HCC) Systemic Therapy
Authors: Lazzaro Alexander , Hartshorn Kevan L.
Published: April 2023

We provide a comprehensive review of current approved systemic treatment strategies for advanced hepatocellular carcinoma (HCC), starting with the phase III clinical trial of sorafenib which was the first to definitively show a survival benefit. After this trial, there was an initial period of little progress. However, in recent years, an explosion of new agents and combinations of agents has resulted in a markedly improved outlook for patients. We then provide the authors’ current approach to therapy, i.e., “How We Treat HCC”. Promising future directions and important gaps in therapy that persist are finally reviewed. HCC is a highly prevalent cancer worldwide and the incidence is growing due not only to alcoholism, hepatitis B and C, but also to steatohepatitis. HCC, like renal cell carcinoma and melanoma, is a cancer largely resistant to chemotherapy but the advent of anti-angiogenic, targeted and immune therapies have improved survival for all of these cancers. We hope this review will heighten interest in the field of HCC therapies, provide a clear outline of the current data and strategy for treatment, and sensitize readers to new developments that are likely to emerge in the near future.
Brugada Syndrome within Asian Populations: State-of-the-Art Review
Authors: Khawaja Muzamil , Qadeer Yusuf Kamran , Siddiqui Rehma , Chelu Mihail G. , Aiumtrakul Noppawit , Pickett June K. , Brugada Ramon , Brugada Josep , Brugada Pedro , Krittanawong Chayakrit
Published: April 2023

Brugada syndrome (BrS) is an inherited cardiac channelopathy with variable expressivity that can lead to sudden cardiac arrest (SCA). Studies worldwide suggest that BrS and Brugada pattern (BrP) have low prevalences in general. However, studies also note that BrS is most prevalent among certain Asian populations. Among the different global regions, the highest prevalence is believed to be in Southeast Asia, followed by the Middle East, South Asia, East Asia, Europe, and North America. It is not only important to recognize such varying degrees of BrS prevalence within Asia but also to understand that there may be significant differences in terms of presenting symptoms, occult risk factors, and the impact on clinical outcomes. The importance of identifying such differences lies in the necessity to develop improved risk assessment strategies to guide secondary prevention and treatment for these patients. Specifically, the decision to pursue placement of an implantable cardiac defibrillator (ICD) can be lifesaving for high-risk BrS patients. However, there remains a significant lack of consensus on how to best risk stratify BrS patients. While the current guidelines recommend ICD implantation in patients with spontaneous Type 1 ECG pattern BrS who present with syncope, there may still exist additional clinical factors that may serve as better predictors or facilitate more refined risk stratification before malignant arrhythmias occur. This carries huge relevance given that BrS patients often do not have any preceding symptoms prior to SCA. This review seeks to delineate the differences in BrS presentation and prevalence within the Asian continent in the hope of identifying potential risk factors to guide better prognostication and management of BrS patients in the future.
Recent Advances in Electrocatalysts for Ammonia Oxidation Reaction
Authors: Jang Ji Hee , Park So Young , Youn Duck Hyun , Jang Youn Jeong
Published: April 2023

Ammonia (NH3) is a clean energy source that can either be directly used as fuel or a hydrogen carrier due to its high energy density and high hydrogen content. The NH3 electro-oxidation reaction (AOR) is the main reaction in both direct NH3 fuel cells and NH3 electrolysis. The AOR is thermodynamically favorable; however, the sluggish kinetics of the reaction can result in issues such as high overpotential, slow reaction rate, deactivation, etc. To overcome this, multiple strategies have been discussed to develop electrocatalysts that maintain a robust reaction rate in low overpotential regions. In this review, the fundamentals of AOR, including thermodynamics, kinetics, and experimental techniques, are studied. This review also focused on recent progress for catalyst modifications and their effects, with a particular focus on Pt- or Ni-based electrocatalysts. Additionally, vacant rooms needed to be developed was pointed, and a way to overcome the limitations was suggested. The fundamentals and efforts to prepare catalysts reviewed in this work will be effective in proposing and designing new robust electrocatalysts leading to advance AOR in practice.
Pivotal Role of Ni/ZrO2 Phase Boundaries for Coke-Resistant Methane Dry Reforming Catalysts
Authors: Haug Leander , Thurner Christoph , Bekheet Maged F. , Ploner Kevin , Bischoff Benjamin , Gurlo Aleksander , Kunz Martin , Sartory Bernhard , Penner Simon , Klötzer Bernhard
Published: April 2023

To identify the synergistic action of differently prepared Ni-ZrO2 phase boundaries in methane dry reforming, we compared an “inverse” near-surface intermetallic NiZr catalyst precursor with the respective bulk-intermetallic NixZry material and a supported Ni-ZrO2 catalyst. In all three cases, stable and high methane dry reforming activity with enhanced anticoking properties can be assigned to the presence of extended Ni-ZrO2 phase boundaries, which result from in situ activation of the intermetallic Ni-Zr model catalyst systems under DRM conditions. All three catalysts operate bifunctionally; methane is essentially decomposed to carbon at the metallic Ni0 surface sites, whereas CO2 reacts to CO at reduced Zr centers induced by a spillover of carbon to the phase boundaries. On pure bulk Ni0, dissolved carbon accumulates in surface-near regions, leading to a sufficiently supersaturated state for completely surface-blocking graphitic carbon segregation. In strong contrast, surface-ZrO2 modified bulk Ni0 exhibits virtually the best decoking and carbon conversion conditions due to the presence of highly dispersed ZrO2 islands with a particularly large contribution of interfacial Ni0-ZrO2 sites and short C-diffusion pathways to the latter.
Al2O3 Nanorod with Rich Pentacoordinate Al3+ Sites Stabilizing Co2+ for Propane Dehydrogenation
Authors: Zhao Zhiping , Wang Zhixia , Tong Yanbing , Sun Jinru , Ke Ming , Song Weiyu
Published: April 2023

The search for inexpensive, environmentally friendly, and highly effective catalysts to activate C-H bonds in propane dehydrogenation (PDH) reactions is still a major challenge. Co-based catalysts have gained significant attention in recent years due to their excellent ability to activate C-H bonds and their high selectivity towards olefins, despite being a non-noble and environmentally unfriendly metal. However, further improvements are necessary for practical utilization, particularly in terms of activity and anti-carbon deposition capacity. In this study, we synthesized Al2O3 nanorods with abundant pentacoordinated Al3+ (Al3+penta) sites. The supported Co on the Al2O3 nanorod (Co/Al2O3-NR) exhibited higher selectivity (>96% propylene selectivity) and stability (deactivation rate 0.15 h−1) compared to Co supported on an Al2O3 nanosheet with fewer pentacoordinated Al3+ sites. Various characterizations confirmed that Co(II) mainly exists as CoAl2O4 rather than Co3O4 in the form of Co/Al2O3-NR, which inhibits the reduction of Co(II) to Co0 and accordingly improves catalyst stability.
Deletion of Cd44 Inhibits Metastasis Formation of Liver Cancer in Nf2-Mutant Mice
Authors: Gerardo-Ramírez Monserrat , Giam Vanessa , Becker Diana , Groth Marco , Hartmann Nils , Morrison Helen , May-Simera Helen L. , Radsak Markus P. , Marquardt Jens U. , Galle Peter R. , Herrlich Peter , Straub Beate K. , Hartmann Monika
Published: April 2023

Primary liver cancer is the third leading cause of cancer-related death worldwide. An increasing body of evidence suggests that the Hippo tumor suppressor pathway plays a critical role in restricting cell proliferation and determining cell fate during physiological and pathological processes in the liver. Merlin (Moesin-Ezrin-Radixin-like protein) encoded by the NF2 (neurofibromatosis type 2) gene is an upstream regulator of the Hippo signaling pathway. Targeting of Merlin to the plasma membrane seems to be crucial for its major tumor-suppressive functions; this is facilitated by interactions with membrane-associated proteins, including CD44 (cluster of differentiation 44). Mutations within the CD44-binding domain of Merlin have been reported in many human cancers. This study evaluated the relative contribution of CD44- and Merlin-dependent processes to the development and progression of liver tumors. To this end, mice with a liver-specific deletion of the Nf2 gene were crossed with Cd44-knockout mice and subjected to extensive histological, biochemical and molecular analyses. In addition, cells were isolated from mutant livers and analyzed by in vitro assays. Deletion of Nf2 in the liver led to substantial liver enlargement and generation of hepatocellular carcinomas (HCCs), intrahepatic cholangiocarcinomas (iCCAs), as well as mixed hepatocellular cholangiocarcinomas. Whilst deletion of Cd44 had no influence on liver size or primary liver tumor development, it significantly inhibited metastasis formation in Nf2-mutant mice. CD44 upregulates expression of integrin β2 and promotes transendothelial migration of liver cancer cells, which may facilitate metastatic spreading. Overall, our results suggest that CD44 may be a promising target for intervening with metastatic spreading of liver cancer.
Z-Disk-Associated Plectin (Isoform 1d): Spatial Arrangement, Interaction Partners, and Role in Filamin C Homeostasis
Authors: Winter Lilli , Staszewska-Daca Ilona , Zittrich Stefan , Elhamine Fatiha , Zrelski Michaela M. , Schmidt Katy , Fischer Irmgard , Jüngst Christian , Schauss Astrid , Goldmann Wolfgang H. , Stehle Robert , Wiche Gerhard
Published: April 2023

Plectin, a highly versatile cytolinker protein, is crucial for myofiber integrity and function. Accordingly, mutations in the human gene (PLEC) cause several rare diseases, denoted as plectinopathies, with most of them associated with progressive muscle weakness. Of several plectin isoforms expressed in skeletal muscle and the heart, P1d is the only isoform expressed exclusively in these tissues. Using high-resolution stimulated emission depletion (STED) microscopy, here we show that plectin is located within the gaps between individual α-actinin-positive Z-disks, recruiting and bridging them to desmin intermediate filaments (Ifs). Loss of plectin in myofibril bundles led to a complete loss of desmin Ifs. Loss of Z-disk-associated plectin isoform P1d led to disorganization of muscle fibers and slower relaxation of myofibrils upon mechanical strain, in line with an observed inhomogeneity of muscle ultrastructure. In addition to binding to α-actinin and thereby providing structural support, P1d forms a scaffolding platform for the chaperone-assisted selective autophagy machinery (CASA) by directly interacting with HSC70 and synpo2. In isoform-specific knockout (P1d-KO) mouse muscle and mechanically stretched plectin-deficient myoblasts, we found high levels of undigested filamin C, a bona fide substrate of CASA. Similarly, subjecting P1d-KO mice to forced swim tests led to accumulation of filamin C aggregates in myofibers, highlighting a specific role of P1d in tension-induced proteolysis activated upon high loads of physical exercise and muscle contraction.
Characterization of Two Parabacteroides distasonis Candidate Strains as New Live Biotherapeutics against Obesity
Authors: Cuffaro Bernardo , Boutillier Denise , Desramaut Jérémy , Jablaoui Amin , Werkmeister Elisabeth , Trottein François , Waligora-Dupriet Anne-Judith , Rhimi Moez , Maguin Emmanuelle , Grangette Corinne
Published: April 2023

The gut microbiota is now considered as a key player in the development of metabolic dysfunction. Therefore, targeting gut microbiota dysbiosis has emerged as a new therapeutic strategy, notably through the use of live gut microbiota-derived biotherapeutics. We previously highlighted the anti-inflammatory abilities of two Parabacteroides distasonis strains. We herein evaluate their potential anti-obesity abilities and show that the two strains induced the secretion of the incretin glucagon-like peptide 1 in vitro and limited weight gain and adiposity in obese mice. These beneficial effects are associated with reduced inflammation in adipose tissue and the improvement of lipid and bile acid metabolism markers. P. distasonis supplementation also modified the Actinomycetota, Bacillota and Bacteroidota taxa of the mice gut microbiota. These results provide better insight into the capacity of P. distasonis to positively influence host metabolism and to be used as novel source of live biotherapeutics in the treatment and prevention of metabolic-related diseases.