bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual Reality and Augmented Reality in Plastic and Craniomaxillofacial Surgery: A Scoping Review
Authors: Kaplan Nicolas , Marques Mitchell , Scharf Isabel , Yang Kevin , Alkureishi Lee , Purnell Chad , Patel Pravin , Zhao Linping
Published: April 2023

Virtual reality (VR) and augmented reality (AR) have evolved since their introduction to medicine in the 1990s. More powerful software, the miniaturization of hardware, and greater accessibility and affordability enabled novel applications of such virtual tools in surgical practice. This scoping review aims to conduct a comprehensive analysis of the literature by including all articles between 2018 and 2021 pertaining to VR and AR and their use by plastic and craniofacial surgeons in a clinician-as-user, patient-specific manner. From the initial 1637 articles, 10 were eligible for final review. These discussed a variety of clinical applications: perforator flaps reconstruction, mastectomy reconstruction, lymphovenous anastomosis, metopic craniosynostosis, dermal filler injection, auricular reconstruction, facial vascularized composite allotransplantation, and facial artery mapping. More than half (60%) involved VR/AR use intraoperatively with the remainder (40%) examining preoperative use. The hardware used predominantly comprised HoloLens (40%) and smartphones (40%). In total, 9/10 Studies utilized an AR platform. This review found consensus that VR/AR in plastic and craniomaxillofacial surgery has been used to enhance surgeons’ knowledge of patient-specific anatomy and potentially facilitated decreased intraoperative time via preoperative planning. However, further outcome-focused research is required to better establish the usability of this technology in everyday practice.
Factors Limiting Radial Growth of Conifers on Their Semiarid Borders across Kazakhstan
Authors: Mapitov Nariman B. , Belokopytova Liliana V. , Zhirnova Dina F. , Abilova Sholpan B. , Ualiyeva Rimma M. , Bitkeyeva Aliya A. , Babushkina Elena A. , Vaganov Eugene A.
Published: April 2023

The forests of Central Asia are biodiversity hotspots at risk from rapid climate change, but they are understudied in terms of the climate–growth relationships of trees. This classical dendroclimatic case study was performed for six conifer forest stands near their semiarid boundaries across Kazakhstan: (1–3) Pinus sylvestris L., temperate forest steppes; (4–5) Picea schrenkiana Fisch. & C.A. Mey, foothills, the Western Tien Shan, southeast; (6) Juniperus seravschanica Kom., montane zone, the Western Tien Shan, southern subtropics. Due to large distances, correlations between local tree-ring width (TRW) chronologies are significant only within species (pine, 0.19–0.50; spruce, 0.55). The most stable climatic response is negative correlations of TRW with maximum temperatures of the previous (from −0.37 to −0.50) and current (from −0.17 to −0.44) growing season. The strength of the positive response to annual precipitation (0.10–0.48) and Standardized Precipitation Evapotranspiration Index (0.15–0.49) depends on local aridity. The timeframe of climatic responses shifts to earlier months north-to-south. For years with maximum and minimum TRW, differences in seasonal maximal temperatures (by ~1–3 °C) and precipitation (by ~12–83%) were also found. Heat stress being the primary factor limiting conifer growth across Kazakhstan, we suggest experiments there on heat protection measures in plantations and for urban trees, alongside broadening the coverage of the dendroclimatic net with accents on the impact of habitat conditions and climate-induced long-term growth dynamics.
COVID-19, Blood Lipid Changes, and Thrombosis
Authors: Farooqui Akhlaq A. , Farooqui Tahira , Sun Grace Y. , Lin Teng-Nan , Teh Daniel B. L. , Ong Wei-Yi
Published: April 2023

Although there is increasing evidence that oxidative stress and inflammation induced by COVID-19 may contribute to increased risk and severity of thromboses, the underlying mechanism(s) remain to be understood. The purpose of this review is to highlight the role of blood lipids in association with thrombosis events observed in COVID-19 patients. Among different types of phospholipases A2 that target cell membrane phospholipids, there is increasing focus on the inflammatory secretory phospholipase A2 IIA (sPLA2-IIA), which is associated with the severity of COVID-19. Analysis indicates increased sPLA2-IIA levels together with eicosanoids in the sera of COVID patients. sPLA2 could metabolise phospholipids in platelets, erythrocytes, and endothelial cells to produce arachidonic acid (ARA) and lysophospholipids. Arachidonic acid in platelets is metabolised to prostaglandin H2 and thromboxane A2, known for their pro-coagulation and vasoconstrictive properties. Lysophospholipids, such as lysophosphatidylcholine, could be metabolised by autotaxin (ATX) and further converted to lysophosphatidic acid (LPA). Increased ATX has been found in the serum of patients with COVID-19, and LPA has recently been found to induce NETosis, a clotting mechanism triggered by the release of extracellular fibres from neutrophils and a key feature of the COVID-19 hypercoagulable state. PLA2 could also catalyse the formation of platelet activating factor (PAF) from membrane ether phospholipids. Many of the above lipid mediators are increased in the blood of patients with COVID-19. Together, findings from analyses of blood lipids in COVID-19 patients suggest an important role for metabolites of sPLA2-IIA in COVID-19-associated coagulopathy (CAC).
Mitochondrial DNA Changes in Respiratory Complex I Genes in Brain Gliomas
Authors: Kozakiewicz Paulina , Grzybowska-Szatkowska Ludmiła , Ciesielka Marzanna , Całka Paulina , Osuchowski Jacek , Szmygin Paweł , Jarosz Bożena , Ostrowska-Leśko Marta , Dudka Jarosław , Tkaczyk-Wlizło Angelika , Ślaska Brygida
Published: April 2023

Mitochondria are organelles necessary for oxidative phosphorylation. The interest in the role of mitochondria in the process of carcinogenesis results from the fact that a respiratory deficit is found in dividing cells, especially in cells with accelerated proliferation. The study included tumor and blood material from 30 patients diagnosed with glioma grade II, III and IV according to WHO (World Health Organization). DNA was isolated from the collected material and next-generation sequencing was performed on the MiSeqFGx apparatus (Illumina). The study searched for a possible relationship between the occurrence of specific mitochondrial DNA polymorphisms in the respiratory complex I genes and brain gliomas of grade II, III and IV. The impact of missense changes on the biochemical properties, structure and functioning of the encoded protein, as well as their potential harmfulness, were assessed in silico along with their belonging to a given mitochondrial subgroup. The A3505G, C3992T, A4024G, T4216C, G5046A, G7444A, T11253C, G12406A and G13604C polymorphisms were assessed as deleterious changes in silico, indicating their association with carcinogenesis.
Effects of Cold Atmospheric Plasma Pre-Treatment of Titanium on the Biological Activity of Primary Human Gingival Fibroblasts
Authors: Gund Madline P. , Naim Jusef , Lehmann Antje , Hannig Matthias , Linsenmann Constanze , Schindler Axel , Rupf Stefan
Published: April 2023

Cold atmospheric plasma treatment (CAP) enables the contactless modification of titanium. This study aimed to investigate the attachment of primary human gingival fibroblasts on titanium. Machined and microstructured titanium discs were exposed to cold atmospheric plasma, followed by the application of primary human gingival fibroblasts onto the disc. The fibroblast cultures were analyzed by fluorescence, scanning electron microscopy and cell-biological tests. The treated titanium displayed a more homogeneous and denser fibroblast coverage, while its biological behavior was not altered. This study demonstrated for the first time the beneficial effect of CAP treatment on the initial attachment of primary human gingival fibroblasts on titanium. The results support the application of CAP in the context of pre-implantation conditioning, as well as of peri-implant disease treatment.
Investigating Urine Biomarkers in Detrusor Underactivity and Detrusor Overactivity with Detrusor Underactivity Patients
Authors: Jiang Yuan-Hong , Jhang Jia-Fong , Wu Ya-Hui , Kuo Hann-Chorng
Published: April 2023

Bladder inflammation and tissue hypoxia were considered important pathognomonic bladder features in detrusor underactivity (DU) and detrusor overactivity (DO) patients. This study investigated urine inflammatory and oxidative stress biomarker levels in DU and DO with DU (DO-DU) patients. Urine samples were collected from 50 DU and 18 DO-DU patients, as well as 20 controls. The targeted analytes included three oxidative stress biomarkers (8-OHdG, 8-isoprostane, and total antioxidant capacity [TAC]) and 33 cytokines. DU and DO-DU patients had different urine biomarker profiles from controls, including 8-OHdG, PGE2, EGF, TNFα, IL-1β, IL-5, IL-6, IL-8, IL-10, IL-17A, and CXCL10. Controlling for age and sex, multivariate logistic-regression models revealed that 8-OHdG, PGE2, EGF, IL-5, IL-8, IL-10, and TAC were significant biomarkers for diagnosing DU. In DU patients, urine TAC and PGE2 levels were positively correlated with detrusor voiding pressure. In DO-DU patients, urine 8-OHdG, PGE2, IL-6, IL-10, and MIP-1α levels were positively correlated with maximal urinary flow rate, while urine IL-5, IL-10, and MIP-1α were negatively correlated with the first sensation of bladder filling. Urine inflammatory and oxidative stress biomarker analysis provides a non-invasive and convenient approach for important clinical information in DU and DO-DU patients.
Age-Dependent Changes in Calcium Regulation after Myocardial Ischemia–Reperfusion Injury
Authors: Bencurova Maria , Lysikova Terezia , Leskova Majdova Katarina , Kaplan Peter , Racay Peter , Lehotsky Jan , Tatarkova Zuzana
Published: April 2023

During aging, heart structure and function gradually deteriorate, which subsequently increases susceptibility to ischemia–reperfusion (IR). Maintenance of Ca2+ homeostasis is critical for cardiac contractility. We used Langendorff’s model to monitor the susceptibility of aging (6-, 15-, and 24-month-old) hearts to IR, with a specific focus on Ca2+-handling proteins. IR, but not aging itself, triggered left ventricular changes when the maximum rate of pressure development decreased in 24-month-olds, and the maximum rate of relaxation was most affected in 6-month-old hearts. Aging caused a deprivation of Ca2+-ATPase (SERCA2a), Na+/Ca2+ exchanger, mitochondrial Ca2+ uniporter, and ryanodine receptor contents. IR-induced damage to ryanodine receptor stimulates Ca2+ leakage in 6-month-old hearts and elevated phospholamban (PLN)-to-SERCA2a ratio can slow down Ca2+ reuptake seen at 2–5 μM Ca2+. Total and monomeric PLN mirrored the response of overexpressed SERCA2a after IR in 24-month-old hearts, resulting in stable Ca2+-ATPase activity. Upregulated PLN accelerated inhibition of Ca2+-ATPase activity at low free Ca2+ in 15-month-old after IR, and reduced SERCA2a content subsequently impairs the Ca2+-sequestering capacity. In conclusion, our study suggests that aging is associated with a significant decrease in the abundance and function of Ca2+-handling proteins. However, the IR-induced damage was not increased during aging.
Protein Delivery to Insect Epithelial Cells In Vivo: Potential Application to Functional Molecular Analysis of Proteins in Butterfly Wing Development
Authors: Nakazato Yugo , Otaki Joji M.
Published: April 2023

Protein delivery to cells in vivo has great potential for the functional analysis of proteins in nonmodel organisms. In this study, using the butterfly wing system, we investigated a method of protein delivery to insect epithelial cells that allows for easy access, treatment, and observation in real time in vivo. Topical and systemic applications (called the sandwich and injection methods, respectively) were tested. In both methods, green/orange fluorescent proteins (GFP/OFP) were naturally incorporated into intracellular vesicles and occasionally into the cytosol from the apical surface without any delivery reagent. However, the antibodies were not delivered by the sandwich method at all, and were delivered only into vesicles by the injection method. A membrane-lytic peptide, L17E, appeared to slightly improve the delivery of GFP/OFP and antibodies. A novel peptide reagent, ProteoCarry, successfully promoted the delivery of both GFP/OFP and antibodies into the cytosol via both the sandwich and injection methods. These protein delivery results will provide opportunities for the functional molecular analysis of proteins in butterfly wing development, and may offer a new way to deliver proteins into target cells in vivo in nonmodel organisms.
BCI Applications to Creativity: Review and Future Directions, from little-c to C2
Authors: Vanutelli Maria Elide , Salvadore Marco , Lucchiari Claudio
Published: April 2023

BCI devices are increasingly being used to create interactive interfaces between users and their own psychophysiological signals. Over the years, these systems have seen strong development as they can enable people with limited mobility to make certain decisions to alter their environment. Additionally, their portability and ease of use have allowed a field of research to flourish for the study of cognitive and emotional processes in natural settings. The study of creativity, especially little creativity (little-c), is one example, although the results of this cutting-edge research are often poorly systematized. The purpose of the present paper, therefore, was to conduct a scoping review to describe and systematize the various studies that have been conducted on the application potential of BCI to the field of creativity. Twenty-two papers were selected that collect information on different aspects of creativity, including clinical applications; art experience in settings with high ecological validity; BCI for creative content creation, and participants’ engagement. Critical issues and potentialities of this promising area of study are also presented. Implications for future developments towards multi-brain creativity settings and C2 are discussed.
The First-Night Effect on the Instability of Stage N2: Evidence from the Activity of the Central and Autonomic Nervous Systems
Authors: Ma Ning , Ning Qian , Li Mingzhu , Hao Chao
Published: April 2023

A series of studies have suggested that stage N2 is vulnerable and strongly affected by the first-night effect (FNE). However, the neurophysiological mechanism underlying the vulnerability of stage N2 of the FNE has not been well examined. A total of 17 healthy adults (11 women and 6 men, mean age: 21.59 ± 2.12) underwent two nights of polysomnogram recordings in the sleep laboratory. We analyzed sleep structure and central and autonomic nervous system activity during stage N2 and applied the electroencephalographic (EEG) activation index (beta/delta power ratio) and heart rate variability to reflect changes in central and autonomic nervous system activity caused by the FNE. Correlation analyses were performed between EEG activation and heart rate variability. The results showed that EEG activation and high-frequency heart rate variability increased on the adaptation night (Night 1). Importantly, EEG activation was significantly associated with the percentage of stage N1, and the correlation between EEG activation and high-frequency heart rate variability decreased due to the FNE. These findings indicate that the FNE affects the instability of stage N2 by increasing central nervous system activity and uncoupling the activity between the central and autonomic nervous systems.
“When You’re Smiling”: How Posed Facial Expressions Affect Visual Recognition of Emotions
Authors: Benuzzi Francesca , Ballotta Daniela , Casadio Claudia , Zanelli Vanessa , Porro Carlo Adolfo , Nichelli Paolo Frigio , Lui Fausta
Published: April 2023

Facial imitation occurs automatically during the perception of an emotional facial expression, and preventing it may interfere with the accuracy of emotion recognition. In the present fMRI study, we evaluated the effect of posing a facial expression on the recognition of ambiguous facial expressions. Since facial activity is affected by various factors, such as empathic aptitudes, the Interpersonal Reactivity Index (IRI) questionnaire was administered and scores were correlated with brain activity. Twenty-six healthy female subjects took part in the experiment. The volunteers were asked to pose a facial expression (happy, disgusted, neutral), then to watch an ambiguous emotional face, finally to indicate whether the emotion perceived was happiness or disgust. As stimuli, blends of happy and disgusted faces were used. Behavioral results showed that posing an emotional face increased the percentage of congruence with the perceived emotion. When participants posed a facial expression and perceived a non-congruent emotion, a neural network comprising bilateral anterior insula was activated. Brain activity was also correlated with empathic traits, particularly with empathic concern, fantasy and personal distress. Our findings support the idea that facial mimicry plays a crucial role in identifying emotions, and that empathic emotional abilities can modulate the brain circuits involved in this process.
Risk and Adversity Factors in Adult Patients with Comorbid Attention Deficit Hyperactivity Disorder (ADHD), Binge Eating Disorder (BED), and Borderline Personality Disorder (BPD): A Naturalistic Exploratory Study
Authors: Ryan Derek , Sadek Joseph
Published: April 2023

This study was a retrospective pilot chart review of adult attention deficit hyperactivity disorder (ADHD) patients diagnosed with and without comorbid binge eating disorder (BED) and borderline personality disorder (BPD). ADHD research is critical because of its prevalence and persistence into adulthood. In the literature, ADHD, BED, and BPD are linked to an underlying impulsivity factor. This comparative study examined whether differences existed between patient groups concerning risk factors, comorbid disorders, and continuous performance test (CPT) cognitive scoring. The main goal was to find significant associations suggestive of correlations between specific factors and a principal diagnosis of ADHD with comorbid BED and BPD. Study participants were patients between 18 and 30 diagnosed by a psychiatrist in an outpatient clinic between June 2022 and December 2022. Both the control and comorbidity groups included 50 participants (N = 100). Patients were randomly chosen based on the chronological order of intake visit dates at the clinic and were selected as participants upon meeting the inclusion criteria. Data were collected through the Med Access EMR database, with quantitative data analyzed using SPSS and chi-squared p-value tests. The results showed significant associations between a principal diagnosis of ADHD with comorbid BPD and BED and (1) having four or more overall risk factors; (2) having five specific reported psychosocial risk factors: family issues, bullying, poverty, trouble with the law, and physical abuse; and (3) having on average more risk factors and comorbidities as compared to ADHD patients without comorbid BPD and BED. No association was found between low CPT scores and, thus, differential cognitive functionality between groups. This research will inform future study hypotheses to develop the clinical profile of ADHD patients with comorbid BED and BPD.
Characteristic Tests for Waste Mud and Drilling Sludge and Reuse of Solidification from Plateau Ecological Reserve
Authors: Chen Zhimin , Yunas Waqar , Shao Lin , Yuan Qianlong , Zeng Youli , Liu Shimin
Published: April 2023

The global community has recently increased its efforts for sustainability and environmental protection. “Green Building” and “Green Construction” are the two methods of incorporating these environmental concerns into the construction and maintenance of mega infrastructures and highways with the intention of reducing any environmental impact that the infrastructures may have on the local ecosystems and ecology. This paper delves into one such study based on the Qinghai–Jiaxi Highway, which is currently under construction in the Qinghai–Tibet Plateau, China. A water treatment method for construction-related mud and sludge is presented as a solution to prevent environmental contamination in the Qinghai–Tibet Plateau. Several tests are performed on samples collected from the Qinghai–Jiaxi Highway to check the feasibility of this method. Several tests, such as X-ray diffraction, a chemical composition analysis, pH tests, mud density, and quality assessments, are performed for this purpose. Following these tests, mud sample mixtures are strengthened with concrete, and their suitability as a filler for road bases is evaluated using compression tests, in accordance with the GB50107 standard. The test results show that the concrete blocks have a compression strength of 35 MPA, which is well within the required standards. The proposed method helps to reduce the harmful discharges from construction sites into the local ecosystems and can potentially reduce the effluent matter in the Qinghai–Tibet Plateau and Ecological Reserve.
Arsenic, Iron, and Manganese Adsorption in Single and Trinary Heavy Metal Solution Systems by Bamboo-Derived Biochars
Authors: Pinisakul Anawat , Kruatong Nattakarn , Vinitnantharat Soydoa , Wilamas Ponwarin , Neamchan Rattikan , Sukkhee Nareerat , Werner David , Sanghaisuk Saichol
Published: April 2023

Currently, heavy metal-contaminated groundwater is an environmental concern. This study investigated the use of bamboo biochar, chitosan-impregnated biochar, and iron-impregnated biochar for arsenic, iron, and manganese removal from groundwater. Isotherms of arsenic, iron, and manganese adsorption by bamboo derived biochar were compared with those of commercial activated carbon in simulated groundwater composed of single and trinary heavy metal solutions. The binding of heavy metals by virgin and loaded bamboo biochar and activated carbon was also investigated by sequential extraction. Chitosan and iron-impregnated biochar had enhanced arsenic adsorption, but these sorbents turned the pH of solution acidic, while it was alkaline for activated carbon. Adsorption equilibrium times of arsenic and iron were faster for single than trinary heavy metal systems because less ion competition occurred at active sites. The Langmuir model fitted the adsorption data well. The maximum adsorption capacities of arsenic, iron, and manganese by bamboo biochar in trinary heavy metal system were 2.2568, 0.6393, and 1.3541 mg g−1, respectively. The main mechanism for arsenic removal was precipitation with iron. Bamboo biochar bound iron in organic and sulfide fractions and manganese with iron-oxide. Bamboo biochar can replace activated carbon as a more efficient and sustainable carbonaceous sorbent material for removal of mixed heavy metals from groundwater within acceptable pH ranges.
Targeting FLT3 Mutation in Acute Myeloid Leukemia: Current Strategies and Future Directions
Authors: Fedorov Kateryna , Maiti Abhishek , Konopleva Marina
Published: April 2023

FLT3 mutations are present in 30% of newly diagnosed patients with acute myeloid leukemia. Two broad categories of FLT3 mutations are ITD and TKD, with the former having substantial clinical significance. Patients with FLT3-ITD mutation present with a higher disease burden and have inferior overall survival, due to high relapse rates after achieving remission. The development of targeted therapies with FLT3 inhibitors over the past decade has substantially improved clinical outcomes. Currently, two FLT3 inhibitors are approved for use in patients with acute myeloid leukemia: midostaurin in the frontline setting, in combination with intensive chemotherapy; and gilteritinib as monotherapy in the relapsed refractory setting. The addition of FLT3 inhibitors to hypomethylating agents and venetoclax offers superior responses in several completed and ongoing studies, with encouraging preliminary data. However, responses to FLT3 inhibitors are of limited duration due to the emergence of resistance. A protective environment within the bone marrow makes eradication of FLT3mut leukemic cells difficult, while prior exposure to FLT3 inhibitors leads to the development of alternative FLT3 mutations as well as activating mutations in downstream signaling, promoting resistance to currently available therapies. Multiple novel therapeutic strategies are under investigation, including BCL-2, menin, and MERTK inhibitors, as well as FLT3-directed BiTEs and CAR-T therapy.
Response Evaluation after Neoadjuvant Chemotherapy for Resectable Gastric Cancer
Authors: Sandø Alina Desiree , Fougner Reidun , Røyset Elin Synnøve , Dai Hong Yan , Grønbech Jon Erik , Bringeland Erling Audun
Published: April 2023

Background: The method of response evaluation following neoadjuvant chemotherapy (NAC) in resectable gastric cancer has been widely debated. An essential prerequisite is the ability to stratify patients into subsets of different long-term survival rates based on the response mode. Histopathological measures of regression have their limitations, and interest resides in CT-based methods that can be used in everyday settings. Methods: We conducted a population-based study (2007–2016) on 171 consecutive patients with gastric adenocarcinoma who were receiving NAC. Two methods of response evaluation were investigated: a strict radiological procedure using RECIST (downsizing), and a composite radiological/pathological procedure comparing the initial radiological TNM stage to the pathological ypTNM stage (downstaging). Clinicopathological variables that could predict the response were searched for, and correlations between the response mode and long-term survival rates were assessed. Results: RECIST failed to identify half of the patients progressing to metastatic disease, and it was unable to assign patients to subsets with different long-term survival rates based on the response mode. However, the TNM stage response mode did achieve this objective. Following re-staging, 48% (78/164) were downstaged, 15% (25/164) had an unchanged stage, and 37% (61/164) were upstaged. A total of 9% (15/164) showed a histopathological complete response. The 5-year overall survival rate was 65.3% (95% CI 54.7–75.9%) for TNM downstaged cases, 40.0% (95% CI 20.8–59.2%) for stable disease, and 14.8% (95% CI 6.0–23.6%) for patients with TNM progression, p < 0.001. In a multivariable ordinal regression model, the Lauren classification and tumor site were the only significant determinants of the response mode. Conclusions: Downsizing, as a method for evaluating the response to NAC in gastric cancer, is discouraged. TNM re-staging by comparing the baseline radiological CT stage to the pathological stage following NAC is suggested as a useful method that may be used in everyday situations.
Surgical and Oncological Outcomes of Salvage Hepatectomy for Locally Recurrent Hepatocellular Carcinoma after Locoregional Therapy: A Single-Institution Experience
Authors: Minagawa Takuya , Itano Osamu , Kitago Minoru , Abe Yuta , Yagi Hiroshi , Hibi Taizo , Shinoda Masahiro , Ojima Hidenori , Sakamoto Michiie , Kitagawa Yuko
Published: April 2023

Surgical and oncological outcomes of hepatectomy for recurrent hepatocellular carcinoma (HCC) after locoregional therapy, including locally recurrent HCC (LR-HCC), were examined. Among 273 consecutive patients who underwent hepatectomy for HCC, 102 with recurrent HCC were included and retrospectively reviewed. There were 35 patients with recurrent HCC after primary hepatectomy and 67 with recurrent HCC after locoregional therapies. Pathologic review revealed 30 patients with LR-HCC. Background liver function was significantly worse in patients with recurrent HCC after locoregional therapy (p = 0.002). AFP (p = 0.031) and AFP-L3 (p = 0.033) serum levels were significantly higher in patients with LR-HCC. Perioperative morbidities were significantly more frequently observed with recurrent HCC after locoregional therapies (p = 0.048). Long-term outcomes of recurrent HCC after locoregional therapies were worse than those after hepatectomy, though there was no prognostic difference according to the recurrence patterns after locoregional therapies. Multivariate analyses showed that prognostic factors for resected recurrent HCC were previous locoregional therapy (hazard ratio [HR] 2.0; p = 0.005), multiple HCCs (HR 2.8; p < 0.001), and portal venous invasion (HR 2.3; p = 0.001). LR-HCC was not a prognostic factor. In conclusion, salvage hepatectomy for LR-HCC showed worse surgical outcomes but a favorable prognosis.
The Function of NK Cells in Tumor Metastasis and NK Cell-Based Immunotherapy
Authors: Yu Yanlin
Published: April 2023

Metastatic tumors cause the most deaths in cancer patients. Treating metastasis remains the primary goal of current cancer research. Although the immune system prevents and kills the tumor cells, the function of the immune system in metastatic cancer has been unappreciated for decades because tumors are able to develop complex signaling pathways to suppress immune responses, leading them to escape detection and elimination. Studies showed NK cell-based therapies have many advantages and promise for fighting metastatic cancers. We here review the function of the immune system in tumor progression, specifically focusing on the ability of NK cells in antimetastasis, how metastatic tumors escape the NK cell attack, as well as the recent development of effective antimetastatic immunotherapies.
A Novel Score Using Lymphocyte-to-Monocyte Ratio in Blood and Malignant Body Fluid for Predicting Prognosis of Patients with Advanced Ovarian Cancer
Authors: Jeong Min Jin , Yoon Yeo Nyeong , Kang Yeon Kyung , Kim Chan Joo , Nam Hae Seong , Lee Yong Seok
Published: April 2023

(1) Background: The lymphocyte-to-monocyte ratio (LMR), one of the systemic inflammatory markers, has been shown to be associated with prognosis of various solid tumors. However, no study has reported clinical utility of the LMR of malignant body fluid (mLMR) (2) Methods: We retrospectively analyzed clinical data of the final 92 patients of a total of 197 patients with advanced ovarian cancer newly diagnosed from November 2015 and December 2021 using our institute big data. (3) Results: Patients were divided into three groups according to their combined bLMR and mLMR scores (bmLMR score): 2, both bLMR and mLMR were elevated; 1, bLMR or mLMR was elevated; and 0, neither bLMR nor mLMR was elevated. A multivariable analysis confirmed that the histologic grade (p = 0.001), status of residual disease (p < 0.001), and bmLMR score (p < 0.001) were independent predictors of disease progression. A low combined value of bLMR and mLMR was strongly associated with a poor prognosis in patients with ovarian cancer. (4) Conclusions: Although further studies are required to apply our results clinically, this is the first study to validate the clinical value of mLMR for predicting prognosis of patients with advanced ovarian cancer.
Disturbing the Redox Balance Using Buthionine Sulfoximine Radiosensitized Somatostatin Receptor-2 Expressing Pre-Clinical Models to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE
Authors: Delbart Wendy , Marin Gwennaëlle , Stamatopoulos Basile , de Wind Roland , Sirtaine Nicolas , Demetter Pieter , Vercruyssen Marie , Woff Erwin , Karfis Ioannis , Ghanem Ghanem E. , Flamen Patrick , Wimana Zéna
Published: April 2023

Peptide receptor radionuclide therapy with 177Lu-DOTATATE improves the outcome of patients with somatostatin receptor (SSTR)-expressing neuroendocrine tumours. Nevertheless, stable disease has been the main response pattern observed, with some rare complete responses. Lu-177 exerts about two-thirds of its biological effects via the indirect effects of ionizing radiation that generate reactive oxygen species, eventually leading to oxidative damage and cell death. This provides a rationale for targeting the antioxidant defence system in combination with 177Lu-DOTATATE. In the present study, the radiosensitizing potential and the safety of depleting glutathione (GSH) levels using buthionine sulfoximine (BSO) during 177Lu-DOTATATE therapy were assessed in vitro and in vivo using a xenograft mouse model. In vitro, the combination resulted in a synergistic effect in cell lines exhibiting a BSO-mediated GSH decrease. In vivo, BSO neither influenced 177Lu-DOTATATE biodistribution nor induced liver, kidney or bone marrow toxicity. In terms of efficacy, the combination resulted in reduced tumour growth and metabolic activity. Our results showed that disturbing the cell redox balance using a GSH synthesis inhibitor increased 177Lu-DOTATATE efficacy without additional toxicity. Targeting the antioxidant defence system opens new safe treatment combination opportunities with 177Lu-DOTATATE.
Platelet-Based Liquid Biopsies through the Lens of Machine Learning
Authors: Cygert Sebastian , Pastuszak Krzysztof , Górski Franciszek , Sieczczyński Michał , Juszczyk Piotr , Rutkowski Antoni , Lewalski Sebastian , Różański Robert , Jopek Maksym Albin , Jassem Jacek , Czyżewski Andrzej , Wurdinger Thomas , Best Myron G. , Żaczek Anna J. , Supernat Anna
Published: April 2023

Liquid biopsies offer minimally invasive diagnosis and monitoring of cancer disease. This biosource is often analyzed using sequencing, which generates highly complex data that can be used using machine learning tools. Nevertheless, validating the clinical applications of such methods is challenging. It requires: (a) using data from many patients; (b) verifying potential bias concerning sample collection; and (c) adding interpretability to the model. In this work, we have used RNA sequencing data of tumor-educated platelets (TEPs) and performed a binary classification (cancer vs. no-cancer). First, we compiled a large-scale dataset with more than a thousand donors. Further, we used different convolutional neural networks (CNNs) and boosting methods to evaluate the classifier performance. We have obtained an impressive result of 0.96 area under the curve. We then identified different clusters of splice variants using expert knowledge from the Kyoto Encyclopedia of Genes and Genomes (KEGG). Employing boosting algorithms, we identified the features with the highest predictive power. Finally, we tested the robustness of the models using test data from novel hospitals. Notably, we did not observe any decrease in model performance. Our work proves the great potential of using TEP data for cancer patient classification and opens the avenue for profound cancer diagnostics.
Catalytic Activity of Zn(II) Coordination Polymer Based on a Cyclotriphosphazene-Functionalized Ligand for Removal of Organic Dyes
Authors: Erkovan Ayşen Orhan , Seifi Azam , Aksoy Burcu Topaloğlu , Zorlu Yunus , Khataee Alireza , Çoşut Bünyemin
Published: April 2023

The 3D Zn(II) coordination polymer {[Zn3(L)(4,4′-bpy)]}n (GTU-3) was prepared with a novel hexapod-shaped molecular building block, hexakis(methyl-2-(4-phenoxyphenyl)acetatebenzene) cyclotriphosphazene (H6L1) by solvothermal reaction in dimethylformamide (DMF). Zn(II) coordination polymer was characterized by FTIR, thermal analysis, SEM-EDX, BET, powder X-ray diffraction analysis, and single crystal X-ray diffraction techniques. GTU-3 consists of six crystallographically independent Zn2+ ions, two fully deprotonated cyclophosphazene-based ligands, and two 4,4′-bipyridines (4,4′-bpy). In the complex, the flexible multisite cyclotriphosphazene bridging ligand (H6L) was completely deprotonated. GTU-3 exhibited relatively good catalytic activity toward Rhodamine B (RhB) removal in aqueous solution. A 0.4 g/L amount of GTU-3 could degrade the 10 mg/L solution of RhB up to 76.5% in the presence of peroxymonosulfate (PMS) oxidant in 1 h. The kinetic studies showed that the degradation process followed pseudo-first-order kinetic. By extending the degradation time to 5 h, the degradation efficiency reached 95.3%. Under the same conditions, Methylene Blue (MB) and Acid Red 17 (AR17) dyes were degraded by 86.2% and 52.8%, respectively.
Divergent Reactivity of D-A Cyclopropanes under PTC Conditions, Ring-Opening vs. Decyanation Reaction
Authors: Bisag Giorgiana Denisa , Viola Pietro , Bernardi Luca , Fochi Mariafrancesca
Published: April 2023

The divergent reactivity of D-A cyclopropane, under PTC conditions, is herein reported. Thus, a ring-opening or a decyanation reaction can be achieved by reacting 2-arylcyclopropane-1,1-dicarbonitriles 1 with thioacetic acid in different reaction conditions. The use of solid Cs2CO3 leads unexpectedly to the synthesis of new D-A cyclopropane derivatives via a decyanation reaction, followed by diastereoselective acetylation, whereas the use of an aqueous solution of Cs2CO3 results in a typical ring-opening reaction with the formation of S-thiolate products. Therefore, the use of tailored reaction conditions allows one to obtain either cyclic or open-chain products in moderate to good yields.
Advances in the Application of Acetonitrile in Organic Synthesis since 2018
Authors: Zhong Pinyong , Zhang Linjun , Luo Nianhua , Liu Jinbiao
Published: April 2023

Acetonitrile is commonly used as an organic solvent and can also be used as an important intermediate in organic synthesis. Its widespread use has led to the development of new methods for the synthesis of a variety of important compounds. In the past decades, the conversion reactions of acetonitrile as a building block have become one of the most-attractive fields in organic synthesis. Especially in the field of electrochemical conversions involving acetonitrile, due to its good conductivity and environmentally friendly features, it has become a powerful and compelling tool to afford nitrogen-containing compounds or nitrile-containing compounds. In this review, we mainly discuss the research progress involving acetonitrile in the past five years, covering both conventional synthesis methods and electrochemical synthesis. Besides, a detailed discussion of the substrate scope and mechanistic pathways is provided.
Direct Reprogramming of Resident Non-Myocyte Cells and Its Potential for In Vivo Cardiac Regeneration
Authors: Perveen Sadia , Vanni Roberto , Lo Iacono Marco , Rastaldo Raffaella , Giachino Claudia
Published: April 2023

Cardiac diseases are the foremost cause of morbidity and mortality worldwide. The heart has limited regenerative potential; therefore, lost cardiac tissue cannot be replenished after cardiac injury. Conventional therapies are unable to restore functional cardiac tissue. In recent decades, much attention has been paid to regenerative medicine to overcome this issue. Direct reprogramming is a promising therapeutic approach in regenerative cardiac medicine that has the potential to provide in situ cardiac regeneration. It consists of direct cell fate conversion of one cell type into another, avoiding transition through an intermediary pluripotent state. In injured cardiac tissue, this strategy directs transdifferentiation of resident non-myocyte cells (NMCs) into mature functional cardiac cells that help to restore the native tissue. Over the years, developments in reprogramming methods have suggested that regulation of several intrinsic factors in NMCs can help to achieve in situ direct cardiac reprogramming. Among NMCs, endogenous cardiac fibroblasts have been studied for their potential to be directly reprogrammed into both induced cardiomyocytes and induced cardiac progenitor cells, while pericytes can transdifferentiate towards endothelial cells and smooth muscle cells. This strategy has been indicated to improve heart function and reduce fibrosis after cardiac injury in preclinical models. This review summarizes the recent updates and progress in direct cardiac reprogramming of resident NMCs for in situ cardiac regeneration.
Noncanonical Roles of RAD51
Authors: Thomas Mélissa , Dubacq Caroline , Rabut Elise , Lopez Bernard S. , Guirouilh-Barbat Josée
Published: April 2023

Homologous recombination (HR), an evolutionary conserved pathway, plays a paramount role(s) in genome plasticity. The pivotal HR step is the strand invasion/exchange of double-stranded DNA by a homologous single-stranded DNA (ssDNA) covered by RAD51. Thus, RAD51 plays a prime role in HR through this canonical catalytic strand invasion/exchange activity. The mutations in many HR genes cause oncogenesis. Surprisingly, despite its central role in HR, the invalidation of RAD51 is not classified as being cancer prone, constituting the “RAD51 paradox”. This suggests that RAD51 exercises other noncanonical roles that are independent of its catalytic strand invasion/exchange function. For example, the binding of RAD51 on ssDNA prevents nonconservative mutagenic DNA repair, which is independent of its strand exchange activity but relies on its ssDNA occupancy. At the arrested replication forks, RAD51 plays several noncanonical roles in the formation, protection, and management of fork reversal, allowing for the resumption of replication. RAD51 also exhibits noncanonical roles in RNA-mediated processes. Finally, RAD51 pathogenic variants have been described in the congenital mirror movement syndrome, revealing an unexpected role in brain development. In this review, we present and discuss the different noncanonical roles of RAD51, whose presence does not automatically result in an HR event, revealing the multiple faces of this prominent actor in genomic plasticity.
Pyranine Immobilized on Aminopropyl-Modified Mesoporous Silica Film for Paraquat Detection
Authors: Sombatsri Sudarat , Deekamwong Krittanun , Khemthong Pongtanawat , Prayoonpokarach Sanchai
Published: April 2023

An optical sensor based on pyranine immobilized on aminopropyl-modified mesoporous silica films was developed for paraquat detection in aqueous solutions. An electrochemically assisted self-assembly method was used to deposit mesoporous silica film on fluorine-doped tin oxide glass. The obtained films were modified with various concentrations of 3-aminopropyl triethoxysilane (APTES) before the immobilization of pyranine. Cyclic voltammetry, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and fluorescence spectroscopy were used to characterize the films. Pyranine-immobilized films gave an emission at 506 nm with an excitation at 450 nm. The fluorescence signal was quenched in the presence of paraquat. The films modified with 3% APTES provided the optimum response to paraquat. The developed films had a linear response to paraquat in the concentration range of 1 to 10 ppm at the optimum conditions, with a detection limit of 0.80 ppm. The developed method was used to quantify paraquat in sugarcane peel and tap water samples with satisfactory results.
Enhancing the Potentiometric H2 Sensing of Pr0.1Ce0.9O2−δ Using Fe2O3 Surface Modification
Authors: Wang Liang , Yi Jianxin
Published: April 2023

Monitoring the concentration of hydrogen is very important as it is a flammable and explosive gas. Non-Nernstian potentiometric hydrogen sensors hold promising potentials for the sensitive detection of hydrogen. This paper reports the improved H2-sensing performance of a mixed oxide ion-electron conducting (MIEC) Pr0.1Ce0.9O2−δ (PCO) electrode using Fe2O3 surface modification. The Fe2O3-modified PCO exhibited a high response of −184.29 mV to 1000 ppm H2 at 450 °C. The response values exhibited a linear or logarithmic dependence on the H2 concentration for below or above 20 ppm, respectively. A sensitivity of −74.9 mV/decade in the concentration range of 20–1000 ppm was achieved, and the theoretical limit of detection was calculated to be 343 ppb. Moreover, a power-law relationship between the response time and the concentration value was also found. Electrochemical impedance analyses revealed that the excellent H2-sensing performance may be attributed to the large ratio of the electrochemical activity of the hydrogen oxidation reaction (HOR) over the oxygen exchange reaction (OER). In addition, the distribution of relaxation time (DRT) results reveal that the enhanced electrochemical kinetics caused by H2 presence in air is mainly related to acceleration of the electrode surface processes.
Does Tennis Training Improve Attention? New Approach
Authors: Ünver Şaban , İslamoğlu İzzet , Atan Tülin , Yılmaz Metin , Arslan Hayati , Kaplan Abdurrahim , Şimşek Emre
Published: April 2023

This study aimed to examine the effect of a tennis training program on improving attention. Methods: A total of 40 tennis players from a Tennis Club, 20 in the experimental group (EG) and 20 in the control group (CG), participated in the study. The EG athletes received 40 serve balls from the trainer twice a week for nine weeks. The researcher applied the “d2 attention test” to the EG and CG before and after the nine-week period. Results: After comparing the pretest and posttest attention averages of the experimental group, there was a significant difference in the TN, TN-E, and CP mean scores (p < 0.001). In the comparison of the pretest and posttest attention averages of the CG, there was no significant difference in the TN, TN-E, and CP mean scores (p > 0.05). The comparison of the pretest attention averages of the EG and CG revealed no significant difference in the TN, TN-E, and CP mean scores (p > 0.05). The comparison of the posttest attention averages of the EG and CG revealed a significant difference in the mean scores of TN, TN-E, and CP (p < 0.05). There was a statistically significant difference between the posttest–pretest differences in the TN, TN-E, and CP values of the EG and CG (p < 0.05). Conclusions: The study concluded that tennis training aimed at developing attention improved the results in the attention test.
Appropriate Use of Antibiotic and Principles of Antimicrobial Stewardship in Children
Authors: Aricò Melodie O. , Valletta Enrico , Caselli Désirée
Published: April 2023

Antibiotics account for over 10% of the overall drug expense of the National Health System in Italy in 2021. Their use in children is of particular interest on one side, because acute infections are very common in children, while they build their immunologic library of competence; on the other side, although many acute infections are expected and turn out to be of viral origin, caregivers will often ask the family doctor or primary care attending to reassure them by prescribing antibiotic treatment, although it may often be unnecessary. The inappropriate prescription of antibiotics in children may likely be a source not only of undue economic burden for the public health system but also of increasing development of antimicrobial resistance (AMR). Based on those issues, the inappropriate use of antibiotics in children should be avoided to reduce the risks of unnecessary toxicity, increase in health costs, lifelong effects, and selection of resistant organisms causing undue deaths. Antimicrobial stewardship (AMS) describes a coherent set of actions that ensure an optimal use of antimicrobials to improve patient outcomes while limiting the risk of adverse events including AMR. The aim of this paper is to spread some concept of good use of antibiotics for pediatricians or every other physician involved in the choice to prescribe, or not, antibiotics in children. Several actions could be of help in this process, including the following: (1) identify patients with high probability of bacterial infection; (2) collect samples for culture study before starting antibiotic treatment if invasive bacterial infection is suspected; (3) select the appropriate antibiotic molecule based on local resistance and narrow spectrum for the suspected pathogen(s); avoid multi-antibiotic association; prescribe correct dosage; (4) choose the best route of administration (oral vs. parenteral) and the best schedule of administration for every prescription (i.e., multiple administration for beta lactam); (5) schedule clinical and laboratory re-evaluation with the aim to consider therapeutic de-escalation; (6) stop antibiotic administration as soon as possible, avoiding the application of “antibiotic course”.