bluuebunny/crossref_metadata_2025 huggingface dataset:
Amyloid deposition and small vessel disease are associated with cognitive function in older adults with type 2 diabetes
Authors: Lesman-Segev Orit H. , Golan Sapir , Springer Ramit Ravona , Livny Abigail , Lin Hung-Mo , Yuxia Ouyang , Zadok Maya , Ganmore Ithamar , Heymann Anthony , Hoffmann Chen , Domachevsky Liran , Beeri Michal Schnaider
Published: September 2023

Diabetes is associated with cognitive decline, but the underlying mechanisms are complex and their relationship with Alzheimer’s Disease biomarkers is not fully understood. We assessed the association of small vessel disease (SVD) and amyloid burden with cognitive functioning in 47 non-demented older adults with type-2 diabetes from the Israel Diabetes and Cognitive Decline Study (mean age 78Y, 64% females). FLAIR-MRI, Vizamyl amyloid-PET, and T1W-MRI quantified white matter hyperintensities as a measure of SVD, amyloid burden, and gray matter (GM) volume, respectively. Mean hemoglobin A1c levels and duration of type-2 diabetes were used as measures of diabetic control. Cholesterol level and blood pressure were used as measures of cardiovascular risk. A broad neuropsychological battery assessed cognition. Linear regression models revealed that both higher SVD and amyloid burden were associated with lower cognitive functioning. Additional adjustments for type-2 diabetes-related characteristics, GM volume, and cardiovascular risk did not alter the results. The association of amyloid with cognition remained unchanged after further adjustment for SVD. Our findings suggest that SVD and amyloid pathology may independently contribute to lower cognitive functioning in non-demented older adults with type-2 diabetes, supporting a multimodal approach for diagnosing, preventing, and treating cognitive decline in this population.
Bioinformatic analysis of SEMA4D and its potential clinical value research in pan-cancer
Authors: Guo Wei , Liu Jun-ying , Chen Rong-feng , Tian Wei-jie , Zheng Cheng-chao , Feng Zhong-wen
Published: September 2023

Introduction: SEMA4D is a signaling protein expressed in various tissues, regulating numerous physiological and pathological processes. Recently, it has been reported to be highly expressed in many tumors, contributing to tumor progression by promoting angiogenesis. However, its status in pan-cancer remains unknown.
Methods: Utilizing the Cancer Genome Atlas (TCGA) Data and several public datasets, we conducted a comprehensive assessment of SEMA4D's role in pan-cancer. First, we examined its expression in different types of human tumors and attempted to correlate it with the stage and grade of the tumors analyzed. We alsoperformed survival analysis to investigate the association between SEMA4D upregulation in tumors and clinical outcome. In addition, we investigated the mutated form, its relationship with the infiltration of various immune cells, and the underlying molecular mechanism of SEMA4D in tumor tissues. Various bioinformatics analysis methods were employed, yielding several valid conclusions.
Results: SEMA4D was found to be expressed in multiple tumor types, with differential expression across different tumor grades. It predominantly localizes on the cell membrane and exhibits significant associations with several other proteins. Moreover, the expression of this gene in manytypes of cancers was found to correlate with immune infiltration, mostly showing a positive correlation. Additionally, SEMA4D was observed to promote the expression of immune checkpoints. Conclusion: Our study has preliminarily identified SEMA4D as a potential prognostic factor for pan-cancer and novel biomarkers for screening, offering valuable insights for the development of precise, reliable, and innovative cancer therapies in the current era of precision medicine.
Predictors of Mortality Due to Severe Traumatic Brain Injury: a Prospective Observational Cohort Study With 1-year Analyses
Authors: Gonçalves Jéssica Vaz , Lirio Pedro Henrique Cassaro , Nascimento Lucas Rodrigues , Louzada Carla Bernado , de Almeida Hanna Souza , Vasconcellos Hellen Siler , Ramos Larissa Cunha Silva Santos , Rodrigues Thais Silva , Arêas Fernando Zanela da Silva
Published: September 2023

Background Many predictors are associated with higher risks of hospital mortality due to severe Traumatic Brain Injury (TBI). The identification of these predictive factors is important for reducing morbimortality. Thus, the aim of this study was to identify predictors of mortality due to severe TBI in a trauma referral hospital in Brazil. Methods A prospective observational cohort study was carried out at a trauma referral hospital. All individuals > 18 years old with severe TBI diagnosis were included. Binomial logistic regression analysis was performed for each variable individually to identify possible predictors of in-hospital mortality and death 12 after hospital discharge. Variables considered statistically significant were analyzed in a final binomial logistic regression model and the magnitude of the association was measured by the odds ratio (OR). Results After applying the enrollment criteria, 383 patients were included. Of these, 211 (55%) died, 172 (45%) survived hospitalization and 22 (15%) died within the first year. The mean age was 49 ± 19 years, 309 (81%) individuals were male, and fall (46.5%) was the main cause of injury. Most individuals had Injury Severity Score ≥ 25 (85.2%). On the final binomial logistic regression model, age greater than 65 years (OR = 6.60 95%CI 2.515–17.354) and pupillary changes such as anisocoria (OR = 2.440 95%CI 1.098–5.465) and mydriasis (6.906 95%CI 2.758- 17,293) were independent variables associated with a higher risk of hospital mortality. High respiratory rate (OR = 1.127 95%CI 1.025–1.240) and body temperature (OR = 0.758 0.606–0.949) collected on admission to the emergency room were also predictors of mortality. A higher risk of mortality was associated with values > 25 on the Injury Severity Score (OR = 3.69395%CI 1.556–8.766) and the performance of decompressive craniectomy (OR = 2.644 95%CI 1.343–5.204). Conclusions This study demonstrated higher mortality rate of patients with TBI when compared to other trauma centers in both high-income countries (HICs) and low- and middle-income countries (LMICs). Early clinical factors such as pupillary changes, high values in the ISS, the performance of decompressive craniectomy, increased respiratory rate and low body temperature were associated with a higher risk of hospital mortality. The study highlights the importance of accounting for regional disparities when developing and implementing TBI management strategies worldwide.
Effect of strontium on transcription factors identified by transcriptome analyses of bovine ruminal epithelial cells
Authors: Tan Panpan , Wang Yazhou , Mei Linshan , Loor Juan J , Zhao Chenxu , Kong Yezi , Zeng Fangyuan , Zhao Baoyu , Wang Jianguo
Published: September 2023

Background: Strontium (Sr) has similar physicochemical properties as calcium (Ca) and is often used to evaluate the absorption of this mineral. Because the major route of Ca absorption in the bovine occurs in the rumen, it is essential to understand whether Sr impacts the ruminal epithelial cells and to what extent.
Results: In the present study, RNA sequencing and assembled transcriptome assembly were used to identify transcription factors (TFs), screening and bioinformatics analysis in bovine ruminal epithelial cells treated with Sr. A total of 1405 TFs were identified and classified into 64 families based on an alignment of conserved domains. A total of 174 differently expressed TFs (DE-TFs) were increased and 52 DE-TFs were decreased; the biological process-epithelial cell differentiation was inhibited according to the GSEA-GO analysis of TFs; The GO analysis of DE-TFs was enriched in the DNA binding. Protein-protein interaction network (PPI) found 12 hubs, including SMAD4, SMAD2, SMAD3, SP1, GATA2, NR3C1, PPARG, FOXO1, MEF2A, NCOA2, LEF1, and ETS1, which verified genes expression levels by real-time PCR.
Conclusions: In this study, SMAD2, PPARG, LEF1, ETS1, GATA2, MEF2A, and NCOA2 are potential candidates that could be targeted by Sr to mediate cell proliferation and differentiation, as well as lipid metabolism. Hence, these results enhance the comprehension of Sr in the regulation of transcription factors and provide new insight into the study of Sr biological function in ruminant animals.
Circ-FOXO3 inhibits triple-negative breast cancer progression via interaction with WHSC1
Authors: Chen Danyang , Zeng Shanshan , Qiu Huisi , Yang Minqiang , Lin Xin , Lv Xinwu , Li Pan , Weng Shaojuan , Kou Siyue , Luo Kai , Liu Zongcai , Yi Yanmei , Liu Hao
Published: September 2023

Background. Circular RNAs (circRNAs), a subclass of non-coding RNAs characterized by covalently closed continuous loops, play a key role in tumorigenesis and aggressiveness. However, the potential molecular mechanism of circRNAs in triple-negative breast cancer (TNBC) remains largely unknown. Exploring their roles and mechanisms in TNBC progression may help identify new diagnostic markers and therapeutic targets.
Methods. Differentially expressed circRNAs were identified by RNA sequencing. The expression of circ-FOXO3 was evaluated using Real-time quantitative RT-PCR and RNA in situ hybridization. The impacts of circ-FOXO3 on the TNBC progression were investigated by in vitro and in vivo functional assays. The underlying mechanism of circ-FOXO3 was revealed by Western blot, RNA pull down, mass spectrometry, RNA immunoprecipitation, luciferase assays and rescue experiments.
Results. Here, we identified circ-FOXO3 as a tumor suppressor in TNBC progression. Circ-FOXO3 was predominantly expressed in the cytoplasm and dramatically downregulated in TNBC tissues. Notably, circ-FOXO3 expression was significantly lower in blood samples from patients with TBNC. Low circ-FOXO3 expression in TNBC tissues and blood was associated with lymph node metastasis and unfavorable outcomes in patients with TNBC. In addition, circ-FOXO3 overexpression inhibited the growth, invasion, and metastasis of TNBC cells both in vitro and in vivo. Moreover, we demonstrated that circ-FOXO3 interacts with Wolf-Hirschhorn syndrome candidate 1 (WHSC1) and inhibits WHSC1 activity, resulting in the inhibition of H3K36me2 modifications at the Zeb2 promoter, ultimately inhibiting Zeb2 expression and halting cancer progression.
Conclusion. Taken together, these results reveal the tumor-suppressive functions of circ-FOXO3 in inhibiting WHSC1-mediated H3K36me2 modification of Zeb2, suggesting that circ-FOXO3 could serve as a potential novel predictive prognostic biomarker and therapeutic target for TNBC.
Metagenomic mining and molecular characterization of a psychrophilic GH5-CBM5 cellulase from Krossfjorden sediments, Arctic
Authors: Kachiprath Bhavya , S Neelima , Umar  , P. Athira P. , Thajudeen Jabir , R. Jayachandran P. , Sarasan Manomi , Puthumana Jayesh , R. Chaithanya E. , Philip Rosamma
Published: September 2023

Glycoside hydrolases are cellulases which hydrolyze the glycosidic bond between two or more complex carbohydrates, or between a carbohydrate and a non-carbohydrate fraction, during the degradation of carbohydrate substrates. The current study reports a cellulase coding gene (Cell-KRD) from the Krossfjorden sediment metagenome by PCR based screening. The enzyme structure reveals that the Cell-KRD has a catalytic module (CM) belonging to GH5_2 subfamily, which is connected to a carbohydrate binding module (CBM5) by a much longer linker sequence (LS) than its mesophilic counterparts. Cell-KRD showed similar features with that of psychrophilic cellulases than their mesophilic and thermophilic homologues. The CM of Cell-KRD (GH5_2 subfamily) exhibits a (β/α)8 topology structure which consists a catalytic cleft and a substrate binding pocket. In silico analyses, including molecular docking studies revealed the significant features of Cell-KRD, which enable efficient cellulose hydrolysis in cold environment.
Postoperative Long-term Outcomes of Acute Normovolemic Hemodilution in Pancreatic Cancer: A Propensity Score Matching Analysis
Authors: Wakiya Taiichi , Ishido Keinosuke , Kimura Norihisa , Nagase Hayato , Kanda Taishu , Kubota Shunsuke , Fujita Hiroaki , Takahashi Yoshiya , Yamamoto Takeshi , Kohei Chida , Saito Junichi , Hirota Kazuyoshi , Hakamada Kenichi
Published: September 2023

Purpose
Acute normovolemic hemodilution (ANH) is a useful intraoperative blood conservation technique. However, impact on long-term outcomes in pancreatic ductal adenocarcinoma (PDAC) remains unclear. We investigated the impact of ANH on long-term outcomes of PDAC patients undergoing radical surgery.
Methods
We collected a dataset from 155 resectable PDAC. Patients were categorized according to whether or not they had received intraoperative allogeneic blood transfusion (ABT) or ANH. Postoperative complications, recurrence-free survival (RFS), and disease-specific survival (DSS), before and after propensity score matching (PSM), were compared among patients who did and did not receive ANH, excluding the ABT cohort.
Results
Forty-four (28.4%) were included in the ANH group, and 30 patients (19.4%) in the ABT group; 81 (52.3%) patients, comprising the standard management (STD) group, received neither ANH nor ABT. The ABT group dmonstrated the worst prognosis among them. Before PSM, ANH was significantly associated with decreased RFS (P = 0.043) and DSS (P = 0.029) compared with the STD group. Cox regression analysis identified ANH as an independent prognostic factor for RFS (risk ratio (RR) = 1.696, P = 0.019) and DSS (RR = 1.876, P = 0.009). After PSM, in contrast with short-term outcomes, RFS (median survival time (MST), 12.1 vs. 18.1 months, P = 0.097) and DSS (MST, 32.1 vs. 50.5 months, P = 0.097) in the ANH group were less favorable than those in the STD group.
Conclusion
ANH has more potential negative effects on long-term postoperative outcomes in PDAC than STD, though not as negative as ABT.
Robots at work: new evidence with recent data§
Authors: Almeida Derick , Sequeira Tiago
Published: September 2023

We reassess the relationship between robotization and the growth in labor productivity with more recent data. We discover that the effect of robot density in the growth productivity substantially decreased in the post-2008 period. In this period, the lower positive effect of robot density in the growth of labor productivity is less dependent on the increase in value added. The data analysis dismisses any positive effect of robotization on hours worked. Results are confirmed by several robustness checks, cross-sectional (and panel-data) IV and quantile regression analysis. By means of the quantile regression analysis, we learn that the effect of robots on labor productivity is stronger for low productivity sectors and that in the most recent period, the effect of robotization felt significantly throughout the distribution. This highlights one of the possible sources of stagnation in the era of robotization and have implication both for labor market and R&D policies.
JEL codes: E23, J23, 030
Bidirectional alpha power EEG-neurofeedback during a focused attention meditation practice in novices.
Authors: Soriano Javier R. , de Oca Eduardo Bracho Montes , Karaiskou Angeliki-Ilektra , De Vuyst Hendrik-Jan , Varon Carolina , Alaerts Kaat
Published: September 2023

Neurofeedback and meditation practices are techniques aimed at enhancing awareness and self-regulation. Training of alpha power has been found to increase mindfulness outcomes, and increases in alpha power seem relatively consistent during focused attention meditation practices. Considering the commonalities between these self-regulation techniques, here we examined the trainability of alpha power in the context of a focused attention meditation, to provide novice practitioners with an integrated training to attain improved self-regulation. In a within-subject design, 31 participants (25 women, aged 23.16, range 18–30) engaged in two runs of six trials each, aimed at up-regulation of global alpha absolute power (average of electroencephalography electrodes). Instructions were to focus the attention on a point above the crown of the head, while perceiving continuous auditory feedback. As an active control, participants took part in two alpha power down-regulation runs. Linear mixed-effect analyses showed that alpha power was overall higher during up- compared to down-regulation training. However, subsequent analyses indicated that the differential training effect was predominantly driven by a successful reduction in alpha power during down-regulation training, while the up-regulation training condition did not significantly yield increases. Differential changes in alpha power induced by both trainings were not significantly sustained during a resting-state recording post training. While these results provide insights into the applicability of alpha neurofeedback combined with meditation, future work is needed to establish the most optimal conditions for facilitating training, with successful up-training of alpha likely requiring more training sessions, consistent with the need of regular practice in meditation trainings.
Radiation-induced cutaneous vasculopathy of the breast: a rare case report
Authors: Hilde Van Parijs , Yves Sinove , Marilyn Carprieaux , Mark De Ridder
Published: September 2023

Background
Radiation therapy is often indicated as part of the treatment for breast cancer and is therefore used frequently worldwide. Vasculopathy is a general term used to describe any condition that affects the blood vessels. We present a case report of a patient presenting with vasculopathy as a rare late side effect of radiation therapy to the breast.
Case presentation:
This 66-year-old woman was initially treated with breast-conserving surgery for early-stage receptor-positive left breast carcinoma. She received postoperative radiation therapy and hormonal treatment with tamoxifen. She developed a sudden spontaneous painless ecchymosis spread over the whole irradiated area 1.5 years after finishing her radiation therapy. Tumor relapse was excluded. There was no associated vasculitis. The cause was presumed to be multifactorial. She had a history of smoking and was known to have hyperlipidemia. She had undergone several surgical treatments at the left breast one year after her initial breast-conserving treatment and was taking tamoxifen. Anti-inflammatory medicine and treatments increasing the local blood flow were prescribed. The ecchymosis resolved completely within one month.
Conclusions
Vasculopathy can occur as a rare late side effect of radiation therapy. It can be reversible. Prevention begins with carefully treating precipitating factors.
Stronger genetic differentiation among within-population genetic groups than among populations in Scots pine: new insights into within-population population genetic structuring in a long-lived woody plant
Authors: Danusevičius Darius , Rajora- Om P. , Kavaliauskas Darius , Baliuckas Virgilijus , Augustaitis Algirdas
Published: September 2023

We investigated the presence of spatial genetic groups within forest tree populations and determined if the genetic divergence among these groups is greater than that between populations using Pinus sylvestris as a model species. We genotyped 890 adult trees of Scots pine in six natural populations in Lithuania at 11 nuclear microsatellite loci. We used a Bayesian clustering to identify the within-population genetic groups within each of the six populations. We calculated the differentiation indexes among the genetic groups within each population and among the six populations by ignoring the genetic groups. The clustering revealed 2 to 6 distinct genetic groups of varying size as the most likely genetic structures within populations. The genetic differentiation indexes among the genetic groups within populations were nearly 10-fold greater (FST = 0.012–0.070) than those between the populations (FST =0.003). We conclude on a markedly stronger structuring of genetic variation within populations than between populations of Scots pine in large forest tracts of northerly Europe. Such genetic structures serve as a contributing factor to large within population genetic diversity in northerly conifers. We assume that within population mating in Scots pine is not completely random but rather is stratified into genetic clusters.
Conditioned medium of epidermal neural crest stem cells improved functional recovery and tissue repairing after spinal cord injury by suppressing neuronal apoptosis through the PI3K/AKT signaling pathway
Authors: Ma Ziqian , Liu Tao , Liu Liang , pei yilun , wang tianyi , wang zhijie , guan yun , Zhang Yan , Chen Xueming
Published: September 2023

Aims: This study evaluated the effects of conditioned medium from epidermal neural crest stem cells (EPI-NCSCs-CM) on functional recovery after spinal cord injury (SCI) and investigated the role of PI3K-AKT signaling pathway in regulating the neuronal apoptosis.
Methods: EPI-NCSCs were isolated from 10-day-old rats and cultured for 48 hours and EPI-NCSCs-CM was extracted. H2O2 was used to establish apoptosis model in SHSY-5Y cells. Cell viability and survival rate were assessed using CCK-8 assay and Calcein-AM/PI staining. A SCI contusion model was established in adult Sprague-Dawley rats. Functional recovery was evaluated using the Basso-Bresnahan-Beattie (BBB) scoring system, inclined test, and footprint observation. Electrophysiological recording was used to analyze neurological restoration after SCI. Histological organization was assessed using Hematoxylin-eosin (H&E) staining and Nissl staining. TUNEL staining and ROS detection were applied to measure the apoptosis and oxidative stress levels. Western blot was conducted to detect the expression levels of apoptosis markers and PI3K/AKT signaling-related proteins.
Results: EPI-NCSCs-CM significantly promoted functional and histological rehabilitation in SCI rats by suppressing neuronal apoptosis through regulating PI3K/AKT signaling pathway. In vitro study indicated that EPI-NCSCs-CM administration alleviated neurotoxicity caused by H2O2 in SHSY-5Y cells. The administration of LY294002 (a PI3K inhibitor) implied that the PI3K/AKT signaling pathway plays a vital role in regulating neuronal apoptosis.
Conclusions: This study presents a new strategy for repairing SCI using EPI-NCSCs-CM, and provides evidence that EPI-NCSCs-CM can inhibit neuronal apoptosis by regulating the PI3K/AKT signaling pathway in SCI rats.
Methane production and lignocellulosic degradation of waste from rice, corn and sugarcane by natural co- culture of anaerobic fungi and methanogens
Authors: Kyawt Yin Yin , Aung Min , Xu Yao , Zhou Yaqi , Li Yuqi , Sun Zhanying , Zhu Weiyun , Cheng Yanfen
Published: September 2023

The objective of this study was to determine the effect of natural co-culture of anaerobic fungi and methanogens on the methane production and lignocellulosic degradation of waste from rice, corn and sugarcane. Hu sheep rumen digesta was used to develop a natural co-culture of anaerobic fungus and methanogen. The substrates used in this study were rice straw (RS), rich husk (RH), corn stover (CS), corn cobs (CC), and sugarcane baggage (SB). Production of total gas and methane, utilization rates of reducing sugar, glucose, and xylose, lignocellulosic degradation and the activity of CMCase and xylanase were highest (P < 0.05) in CC, subsequently followed by RS, CS, SB, and RH. The pH was the lowest (P < 0.05) in RH, followed by SB, CS, RS, and CC. The highest formate concentration (P < 0.05) was found in RH, the subsequently followed by SB, CC, CS, and RS. Acetate concentrations were highest (P < 0.05) in CC, then in RS, CS, SB, and RH. Lactate was lowest in CC (P < 0.05), then in RS, CS, RH, and SB. Ethanol was also lowest (P < 0.05) in CC, following RS, CS, SB, and RH. Therefore, the CC and RS have the highest potential, the CS has a moderate potential, and the SB and RH have the lowest potential for methane production and lignocellulosic degradation by natural co-culture of anaerobic fungus and methanogen.
Bootstrap Confidence Intervals for MultipleChange Points Based on Two-Stage Procedures
Authors: Jin Baisuo , Wang Fangwei , Hou Li
Published: September 2023

We consider the problem of constructing the confidence intervals for multiple change points under linear regression models. Based on two-stage procedures(Jin et al, 2016), we utilize the idea of the orthogonal greedy algorithm (OGA)in the cutting stage and the sup-Wald-type test targeted at estimating changepoints is applied in the refining stage. Under some mild conditions, the rates of consistency and asymptotic distribution for the multiple change points estimators are established. We propose a bootstrap procedure for confidence intervals, which adapts to the unknown magnitude of changes and ensures asymptotic validity. These results are evidenced by simulation and real data examples.
Engineered Exosome Delivery of Apoptin as Tumor Therapeutic
Authors: Hao Ruifeng , Liang Yujie
Published: September 2023

Apopotin is a small protein that can specifically induce apoptosis in tumor cells, thereby selectively killing a variety of human cancer cells. However, penetrating the cell membrane is often challenging and exosome is sometimes leveraged to deliver functional molecules into cells. As the expression of fusion lysosomal-associated membrane protein 2b (LAMP-2B) can integrate exogenous proteins into the exosome membrane, we investigated the ability of apoptin-armed exosomes to penetrate tumor cells and induce apoptosis. In this study, the recombinant plasmid Apoptin-EGFP-Lamp2b was constructed and transfected into COS-7 cells. The Apoptin-EGFP-Lamp2b recombinant fusion protein was expressed and rendered apoptin was displayed on the surface of exosomes. Our study showed that the engineered apoptin-containing exosomes could deliver apopotin across the cell membrane into the nucleus. CCK8 cytotoxicity tests demonstrated that apoptin- containing exosomes could specifically target and kill cancer cells. In addition, Hoechst33342 staining and Annexin-V-FITC/PI method were used to observe the ability of exosome mediated apoptin to induce apoptosis. These results showed that the engineered exosome could successfully deliver apoptin into cancer cells and induce apoptosis, indicating that exosomes could be used as a new type of protein delivery platform.This study developed a powerful apoptin- anchored exosome as a potential for tumor-specific therapy.
Development of a serum-based miRNA signature for early detection of pancreatic cancer: a multicenter cohort study
Authors: Huang Jing , Gao Ge , Liu Jianzhou , Ge Yang , Cui Hongtu , Zheng Ren , Wang Jialin , Wang Si , Go Vay Liang (W) , Hu Shen , Liu Yefu , Yang Minwei , Sun Yongwei , Shang Dong , Tian Yantao , Zhang Zhigang , Xiang Zhongyuan , Guo Junchao , Wang Hongyang , Xiao Gary Guishan
Published: September 2023

Background
A grim prognosis of pancreatic cancer (PCa) was attributed to the difficulty in early diagnosis of the disease. Identifying novel biomarkers for early detection of PCa is thus urgent to improve the overall survival rates of patients.
Methods
The study was performed firstly by identification of candidate microRNAs (miRNAs) in formalin-fixed, paraffin-embedded tissues at either early (n = 100) or advanced (n = 100) stages, to that in benign tissues (n = 100) using microarray profiles, and followed by validation in a serum-based cohort study to assess clinical utility of the candidates as a noninvasive biomarker. In the cohorts, a total of 1273 participants including 571 patients with pancreatic ductal adenocarcinoma, 90 patients with chronic pancreatitis, 217 patients with other pancreatic diseases, and 395 healthy controls from four centers were retrospectively recruited as two cohorts including training and validation cohort. The collected serum specimens were analyzed by real-time polymerase chain reaction.
Results
We identified 27 miRNAs that were expressed differentially in both early and advanced stages of PCa tissues as compared to the benign. Of which, the top-four was selected by the criteria of log2(fold change) > 4 and FDR < 0.05 as a panel whose diagnostic efficacy was fully assessed in the serum-based cohorts. Patients with PCa at early-stage were significantly discriminated from healthy controls by the panel with AUCs of 0.971 (95%CI: 0.956–0.987) and 0.933 (95%CI: 0.892–0.974) in the training and validation cohorts, respectively. Furthermore, the panel distinguished early-stage PCa from non-PCa including chronic pancreatitis as well as pancreatic cystic neoplasms with AUCs of 0.924 (95%CI: 0.899–0.949) and 0.861 (95%CI: 0.818–0.903) in the training and validation cohorts, respectively. Moreover, the panel eliminated interference from other digestive tumors with a specificity of 90.2%. Strikingly, this panel exhibited superior to four biomarkers routinely used in clinic, including CA19-9, CA125, CEA and CA242.
Conclusions
A serum-based panel of four miRNAs was developed showing remarkably discriminative ability of early-stage PCa from either healthy controls or other pancreatic diseases, suggesting it may be developed as a novel, noninvasive approach for early screening of PCa in clinic.
Are Authorities Denying or Supporting? Detecting Stance of Authorities Towards Rumors in Twitter
Authors: Haouari Fatima , Elsayed Tamer
Published: September 2023

Several studies examined the leverage of the stance in conversational threads or news articles as a signal for rumor verification. However, none of these studies leveraged the stance of trusted authorities. In this work, we define the task of detecting the stance of authorities towards rumors in Twitter, i.e., whether a tweet from an authority supports the rumor, denies it, or neither. We believe the task is useful to augment the sources of evidence exploited by existing rumor verification models. We construct and release the first Authority STance towards Rumors (AuSTR) dataset, where evidence is retrieved from authority timelines in Arabic Twitter. The collection comprises 811 (rumor tweet, authority tweet) pairs relevant to 292 unique rumors. Due to the relatively limited size of our dataset, we explore the adequacy of existing Arabic datasets of stance towards claims in training BERT-based models for our task, and the effect of augmenting AuSTR with those datasets. Our experiments show that, despite its limited size, a model trained solely on AuSTR with a class-balanced focus loss exhibits a comparable performance to the best studied combination of existing datasets augmented with AuSTR, achieving a performance of 0.84 macro-F1 and 0.78 F1 on debunking tweets. The results indicate that AuSTR can be sufficient for our task without the need for augmenting it with existing stance datasets. Finally, we conduct a thorough failure analysis to gain insights for the future directions on the task.
Electrochemically controlled blinking of fluorophores to enable quantitative stochastic optical reconstruction microscopy (STORM) imaging
Authors: Gooding John , Yang Ying , Ma Yuanqing , Tilley Richard , Gaus Katharina
Published: September 2023

Stochastic optical reconstruction microscopy (STORM) allows widefield imaging with single molecule resolution through calculating the coordinates of individual fluorophores from the separation of the fluorophore emission in both time and space. Such separation is achieved by photoswitching the fluorophores between a long lived OFF state and an emissive ON state. Despite STORM has revolutionizing cellular imaging, molecular counting in complexes remains challenging due to undercounting errors from photobleached or not-recovered dyes and overcounting artifacts from the repetitive and random blinking of the dyes. Herein we show how an electrochemical approach switching fluorophores for STORM (EC-STORM) has greater control over the switching kinetics, emitter density, and recovery yield than possible photochemically. Using EC-STORM, we demonstrate the capability for molecular counting by applying a programmable electrochemical potential to interrupt the photophysics of dyes. That is, the random blinking of dyes is suppressed by a negative potential but the switching ON event can be activated by a short pulsed positive potential, such that the frequency of ON events scales linearly with the number of underlying dyes. This advance will enable EC-STORM being the widely applicable super resolution imaging technique.
Cultural Intelligence and Interpersonal Trust as Drivers for Innovative Work and Intellectual Capital Development at Organizations
Authors: Lentjushenkova Oksana
Published: September 2023

The main purpose of this study is to determine how cultural intelligence and interpersonal trust impact innovative work behaviour and intellectual capital development in organizations. Research conducted by various authors shows that managers with higher levels of cultural intelligence have higher levels of interpersonal trust. As a result, they are more flexible in the adoption and creation of new ideas and solutions. Most of them are not afraid to share their knowledge and experience by accepting different opinions and creating an appropriate organizational culture. It enables an opportunity to strengthen all elements of intellectual capital and facilitates the competitiveness of the organization. Cultural intelligence and interpersonal trust create opportunities for innovative behaviour in organizations by developing intellectual capital. The scientific literature presents various studies about cultural intelligence and its impact on organizational performance. Most of the studies focused on the integration of migrants into the organizations’ work. Currently, the working environment is cross-cultural, especially after the COVID-19 pandemic and considering globalization and digitalization issues. Despite the various benefits of working in a multicultural environment, there are some significant challenges organizations face, such as interpersonal trust development and cultural intelligence. The current study focused on local employees at organizations: 93 managers of higher education institutions from Latvia were interviewed. The author used qualitative and quantitative research methods for data collection and analysis. Semistructured interviews were used for data collection. The research tool was developed on the basis of scientific literature using different statements about interpersonal trust, work engagement and level of cultural intelligence. One of the significant results found during research is that managers with international experience (working or studying abroad) are more critical of working in international teams and building interpersonal trust within cross-cultural teams. This fact could be the research object in future research. The research results can be used for future research exploring factors influencing cultural intelligence development in cross-cultural organizations and its role in innovation development and intellectual capital management.
Knowledge Economy, Innovation and the Universities' Education Role in Saudi Arabia: A Study of Academicians’ Perspectives at the University of Hail
Authors: Thomran Murad , Alshammari Ali Essa A
Published: September 2023

The labour market is witnessing a significant increase in the levels of demand to learn new skills in areas such as data science, artificial intelligence and machine learning, which are among the most prominent features of the new industrial revolution. Universities have a vital function in the knowledge economy and innovation, as they generate and share knowledge through research, education, and creativity. The knowledge economy (KE) and innovation are key drivers of economic growth, as they promote innovation, productivity, and competitiveness. It creates new industries and jobs that require highly skilled workers. Weakness and inadequacy of the educational and research system have been considered as one of the main issues in Saudi Arabia. The aim of this study is to identify the role of universities in the knowledge economy and innovation in Saudi Arabia from the perspective of academics at the University of Hail. To achieve the objective of this research, a cross-sectional explanatory and descriptive research design with a quantitative approach was adopted by the researchers. A sample size of 83 academicians was chosen using a simple random sampling procedure. The analysis method employed was structural equation modelling (SEM) with partial least squares (PLS). The adopted instrument for collecting the data were a survey. The questionnaire measures were based on a 5-point Likert scale. To measure the reliability and validity of the instruments, Cronbach’s alpha, composite reliability, and Fornell-Lacker criterion tests were conducted. The findings of the study revealed that educational curriculum, educational policy, infrastructure, and scientific research have a significant role in (KE) and innovation, whereas the results of teaching methods showed no significant role in (KE) and innovation. To remain competitive in the ever-changing economic landscape, policymakers in Saudi Arabian universities must prioritize curriculum design, infrastructure, teaching methods, policies, and skilled manpower while paying more attention to science, technology, and innovation. In addition, universities should focus on developing the skills of their graduates to meet the demands of the job market. This can be achieved by offering internships and apprenticeships, as well as providing training in soft skills such as communication, teamwork, and problem-solving.
Digital Currencies and Fintech Innovation Technologies for Economic Growth
Authors: Baltgailis Jurijs , Simakhova Anastasiia , Buka Stanislav
Published: September 2023

The transition of the global economy to digital currencies is inevitable. Today’s monetary methods of regulation do not provide a stable and inclusive economy, and central banks will be forced to move on to the implementation of the state digital currency in real practice, which will ultimately allow introducing total control over the use of customer assets and strict business regulation,especially in the field of the shadow economy and tax crimes. The main factors for the transition to digital currencies aretechnological progress, an increase in online transactions, independence from national currencies, and low commissions. Thepurpose of the article is to assess the potential for economic growth of digital currencies and FinTech innovation technologies inthe context of growing government debts. The scientific novelty of the obtained results lies in the construction of a regression model of GDP growth dependence on inflation, government debt and the long-term interest rate. The regression analysis was conducted by building a linear multiple model for selected developed European countries based on statistical data from the European Central Bank, the European Commission, and other Internet resources. The equation of dependence of the GDP of European countries on the selected factors obtained as a result of regression modelling can be practically used to forecast future GDP indicators. The model showed that inflation growth has a negative impact on GDP growth and confirmed that further economic growth is possible with the introduction of digital currency, which will help to reduce the inflationary burden. The issuance of digital currency will be strictly controlled, which will contribute to the formation of an inclusive economy by attracting people who do not have bank accounts to business, and the shadow economy will be reduced. This will create opportunities for real economic growth. It is predicted that the introduction of digital currencies could lead to a faster, moreconvenient, cheaper and more private payment system, which is important for citizens and businesses.
Effects of Deficit Irrigation on Canopy Temperature Dynamics and Physiology of Landscape Groundcovers
Authors: Sapkota Anish , Haghverdi Amir , Merhaut Donald
Published: September 2023

Identifying the irrigation-induced cooling effects from a particular plant species used for urban groundcovers while optimizing the rates of irrigation applications is important in regions with hot and dry summers. A 2-year (2020–21) study was conducted in Riverside, CA, USA, to evaluate the effect of irrigation rates on the canopy temperature dynamics of 10 urban groundcovers. Four reference evapotranspiration (ETo)-based irrigation treatments (20%, 40%, 60%, and 80% ETo) and 10 groundcovers were laid in a randomized complete block design and replicated three times. The effect of irrigation rates on the difference between canopy–air temperature (ΔT), leaf area index (LAI), and stomatal conductance (gs) were evaluated. All response variables were collected between May and October 2020 and 2021. The crop water stress index for five groundcovers was also computed. The ΔT was affected (P < 0.05) by irrigation rates, and groundcovers, including Rhagodia spinescens and Baccharis × ‘Starn Thompson’, maintained the canopy temperature less than the ambient air temperature for all irrigation rates imposed. For most of the groundcovers, the ΔT yielded a strong relationship with LAI (r = –0.41 to –0.73), and gs (r = –0.35 to –0.60). Crop water stress index also showed a strong correlation to normalized difference vegetation index (r = 0.42 to –0.72) and gs (r = –0.57 to –0.64). Irrigation-included cooling was evident in most groundcovers irrigated at higher rates; however, Rhagodia spinescens and Baccharis × ‘Starn Thompson’ were found to perform well in cooling ability and maintaining the canopy growth as evidenced by LAI. Our study showed that proper plant selection and irrigation management could help maintain green spaces and mitigate the urban heat island effect while conserving irrigation water.
WHIM-синдром: обзор литературы и описание двух собственных клинических наблюдений в одной семье
Authors: Марченко Мария Викторовна , Кузнецов Ю. Н. , Лапина А. В. , Михайлова И. А. , Быкова Т. А. , Щеголева Т. С. , Байков В. В. , Кулагин А. Д.
Published: September 2023

WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis) is a rare genetic disease associated with activating germline mutations in the gene encoding chemokine receptor CXCR4. WHIM syndrome is manifested by neutropenia, lymphopenia, infections, and degenerative changes of mature neutrophils with bone marrow myeloid hyperplasia (myelokathexis). Some patients show hypogammaglobulinemia, persistent cutaneous, genital, or elsewhere localized warts. There are also cases of congenital heart defects. The present paper extensively analyzes genetic basis, pathophysiology, clinical manifestations, and diagnosis of WHIM syndrome as well as its treatment options. The paper reports two cases in one family.
История вопроса о роли биопсии костного мозга в системе стадирования классической лимфомы Ходжкина и современный взгляд в эру ПЭТ-КТ (обзор литературы)
Authors: Даниленко Анатолий Александрович , Фалалеева Н. А. , Шахтарина С. В.
Published: September 2023

The staging of Hodgkin lymphoma lays the groundwork for optimal treatment decision making. For a long time, bone marrow assessment has been an integral part of staging. The study of bone marrow involvement in tumor progression includes radiological method and morphological analysis of its core biopsy samples. During the last five decades of using bone marrow core biopsy, the attitude of oncologists and hematologists to this invasive and painful procedure remained ambivalent between denying and affirming the need to carry it out in all or most Hodgkin lymphoma cases. The present review provides the historical background of bone marrow core biopsy and considers its appropriateness for patients with classical Hodgkin lymphoma.
Фолликулярная лимфома 1–3А цитологического типа с наличием или отсутствием t(14;18)(q32;q21): прогноз, выбор противоопухолевой терапии и ее результаты
Authors: Нестерова Екатерина Сергеевна , Звонков E. E. , Ковригина А. М. , Обухова Т. Н. , Бидерман Б. В. , Судариков А. Б. , Мангасарова Я. К. , Магомедова А. У. , Смольянинова А. К. , Куликов С. М. , Паровичникова Е. Н.
Published: September 2023

Aim. To determine the prognostic value of t(14;18)(q32;q21) in follicular lymphoma (FL) of grades 1–3А, to assess the chemotherapy efficacy in “t(14;18)+ FL” and “t(14;18)– FL” patients, and to analyze the cases of ineffective therapy.

Materials & Methods. The retrospective/prospective study carried out at the National Research Center for Hematology in the period of 2001–2022 enrolled 362 patients with newly diagnosed FL of grades 1–3А. Their risk stratification was based on predictive models FLIPI and PPI3 (Personalized Predictive Index[1]). The patients were 30–81 years of age (median 52 years). There were 225 women and 137 men. They received the following regimens: R-B (n = 80), R-CHOP (n = 189), R-CHOP (4 cycles) + R-DHAP (2 cycles) (n = 28), and R-CHOP (4 cycles) + R-DHAP (2 cycles) + auto-HSCT in the first-line therapy (n = 65). For 2 years, maintenance rituximab therapy was administered to all the enrolled patients, whichever drug chemotherapy they received. Standard cytogenetic analysis and FISH were carried out in 265/362 (73 %) patients.

Results. Patients were divided into two comparable groups: “t(14;18)+ FL” (n = 196) and “t(14;18)– FL” (n = 69). Patients without cytogenetics/FISH (n = 97) were excluded from the analysis. In patients without t(14;18), poor prognostic factors, such as grade 3А (p = 0.003) and Ki-67 > 35 % (p = 0.001), were identified significantly more often, and also high PPI3 risk was reported (p = 0.008). No differences (p = 0.84) were detected during FLIPI risk stratification of patients. Bone marrow lesions were observed significantly more often in “t(14;18)+ FL” compared to “t(14;18)– FL” (p = 0.002). The chemotherapy outcomes, such as 2-year EFS and OS, appeared to be considerably worse in “t(14;18)– FL” compared to “t(14;18)+ FL” patients.

Conclusion. The group of FL patients with t(14;18) appeared to be most numerous and more prognostically favorable. Immunochemotherapy regimens R-B and R-CHOP are more justified in the first-line therapy of FL with low PPI3 risk. Therapy outcomes were comparable in efficacy. In intermediate and high PPI3 risk FL patients with t(14;18), the most effective first-line therapy was the one with consistent administration of R-CHOP, R-DHAP, and auto-HSCT. Based on the results of this study, FL of grades 1–3А without t(14;18) can well be considered to be a prognostically unfavorable variant of this malignant lymphoid tumor. The rate of early relapses/progression after the standard immunochemotherapy (R-B and R-CHOP), according to our data, is 60 %. In patients with newly diagnosed FL who received consistent administration of R-CHOP, R-DHAP, and auto-HSCT in the first-line therapy, this rate drops to 30 %. Our results clearly indicate the need for new FL treatment approaches.