bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Basis of the Binding Mode of the Antineoplastic Compound Motixafortide (BL-8040) in the CXCR4 Chemokine Receptor
Authors: Rebolledo-Bustillo Mariana , Garcia-Gomez David , Dávila Eliud Morales , Castro María Eugenia , Caballero Norma A. , Melendez Francisco J. , Baizabal-Aguirre Victor M. , Sanchez-Gaytan Brenda L. , Perez-Aguilar Jose Manuel
Published: February 2023

Modulation of the CXCL12–CXCR4 signaling axis is of the utmost importance due to its central involvement in several pathological disorders, including inflammatory diseases and cancer. Among the different currently available drugs that inhibit CXCR4 activation, motixafortide—a best-in-class antagonist of this GPCR receptor—has exhibited promising results in preclinical studies of pancreatic, breast, and lung cancers. However, detailed information on the interaction mechanism of motixafortide is still lacking. Here, we characterize the motixafortide/CXCR4 and CXCL12/CXCR4 protein complexes by using computational techniques including unbiased all-atom molecular dynamics simulations. Our microsecond-long simulations of the protein systems indicate that the agonist triggers changes associated with active-like GPCR conformations, while the antagonist favors inactive conformations of CXCR4. Detailed ligand–protein analysis indicates the importance of motixafortide’s six cationic residues, all of which established charge–charge interactions with acidic CXCR4 residues. Furthermore, two synthetic bulky chemical moieties of motixafortide work in tandem to restrict the conformations of important residues associated with CXCR4 activation. Our results not only elucidate the molecular mechanism by which motixafortide interacts with the CXCR4 receptor and stabilizes its inactive states, but also provide essential information to rationally design CXCR4 inhibitors that preserve the outstanding pharmacological features of motixafortide.
Identifying Drug Candidates for COVID-19 with Large-Scale Drug Screening
Authors: Wu Yifei , Pegan Scott D. , Crich David , Lou Lei , Mullininx Lauren Nicole , Starling Edward B. , Booth Carson , Chishom Andrew Edward , Chang Kuan Y. , Xie Zhong-Ru
Published: February 2023

Papain-like protease (PLpro) is critical to COVID-19 infection. Therefore, it is a significant target protein for drug development. We virtually screened a 26,193 compound library against the PLpro of SARS-CoV-2 and identified several drug candidates with convincing binding affinities. The three best compounds all had better estimated binding energy than those of the drug candidates proposed in previous studies. By analyzing the docking results for the drug candidates identified in this and previous studies, we demonstrate that the critical interactions between the compounds and PLpro proposed by the computational approaches are consistent with those proposed by the biological experiments. In addition, the predicted binding energies of the compounds in the dataset showed a similar trend as their IC50 values. The predicted ADME and drug-likeness properties also suggested that these identified compounds can be used for COVID-19 treatment.
Genome-Wide Characterization and Gene Expression Analyses of Malate Dehydrogenase (MDH) Genes in Low-Phosphorus Stress Tolerance of Chinese Fir (Cunninghamia lanceolata)
Authors: Lin Yawen , Chen Wanting , Yang Qiang , Zhang Yajing , Ma Xiangqing , Li Ming
Published: February 2023

Malate dehydrogenase (MDH) genes play vital roles in developmental control and environmental stress tolerance in sessile plants by modulating the organic acid–malic acid level. However, MDH genes have not yet been characterized in gymnosperm, and their roles in nutrient deficiency are largely unexplored. In this study, 12 MDH genes were identified in Chinese fir (Cunninghamia lanceolata), namely, ClMDH-1, -2, -3, …, and -12. Chinese fir is one of the most abundant commercial timber trees in China, and low phosphorus has limited its growth and production due to the acidic soil of southern China. According to the phylogenetic analysis, MDH genes were classified into five groups, and Group 2 genes (ClMDH-7, -8, -9, and 10) were only found to be present in Chinese fir but not in Arabidopsis thaliana and Populus trichocarpa. In particular, the Group 2 MDHs also had specific functional domains—Ldh_1_N (malidase NAD-binding functional domain) and Ldh_1_C (malate enzyme C-terminal functional domain)—indicating a specific function of ClMDHs in the accumulation of malate. All ClMDH genes contained the conserved MDH gene characteristic functional domains Ldh_1_N and Ldh_1_C, and all ClMDH proteins exhibited similar structures. Twelve ClMDH genes were identified from eight chromosomes, involving fifteen ClMDH homologous gene pairs, each with a Ka/Ks ratio of <1. The analysis of cis-elements, protein interactions, and transcription factor interactions of MDHs showed that the ClMDH gene might play a role in plant growth and development, and in response to stress mechanisms. The results of transcriptome data and qRT-PCR validation based on low-phosphorus stress showed that ClMDH1, ClMDH6, ClMDH7, ClMDH2, ClMDH4, ClMDH5, ClMDH10 and ClMDH11 were upregulated under low-phosphorus stress and played a role in the response of fir to low-phosphorus stress. In conclusion, these findings lay a foundation for further improving the genetic mechanism of the ClMDH gene family in response to low-phosphorus stress, exploring the potential function of this gene, promoting the improvement of fir genetics and breeding, and improving production efficiency.
Galectin-3 and Blood Group: Binding Properties, Effects on Plasma Levels, and Consequences for Prognostic Performance
Authors: Pozder Carolin , Screever Elles M. , van der Velde A. Rogier , Silljé Herman H. , Suwijn Janne , de Rond Saskia , Kleber Marcus E. , Delgado Graciela , Schuringa Jan Jacob , van Gilst Wiek H. , Meijers Wouter C. , März Winfried , de Boer Rudolf A.
Published: February 2023

Previous studies have reported an association between ABO type blood group and cardiovascular (CV) events and outcomes. The precise mechanisms underpinning this striking observation remain unknown, although differences in von Willebrand factor (VWF) plasma levels have been proposed as an explanation. Recently, galectin-3 was identified as an endogenous ligand of VWF and red blood cells (RBCs) and, therefore, we aimed to explore the role of galectin-3 in different blood groups. Two in vitro assays were used to assess the binding capacity of galectin-3 to RBCs and VWF in different blood groups. Additionally, plasma levels of galectin-3 were measured in different blood groups in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study (2571 patients hospitalized for coronary angiography) and validated in a community-based cohort of the Prevention of Renal and Vascular End-stage Disease (PREVEND) study (3552 participants). To determine the prognostic value of galectin-3 in different blood groups, logistic regression and cox regression models were used with all-cause mortality as the primary outcome. First, we demonstrated that galectin-3 has a higher binding capacity for RBCs and VWF in non-O blood groups, compared to blood group O. Additionally, LURIC patients with non-O blood groups had substantially lower plasma levels of galectin-3 (15.0, 14.9, and 14.0 μg/L in blood groups A, B, and AB, respectively, compared to 17.1 μg/L in blood group O, p < 0.0001). Finally, the independent prognostic value of galectin-3 for all-cause mortality showed a non-significant trend towards higher mortality in non-O blood groups. Although plasma galectin-3 levels are lower in non-O blood groups, the prognostic value of galectin-3 is also present in subjects with a non-O blood group. We conclude that physical interaction between galectin-3 and blood group epitopes may modulate galectin-3, which may affect its performance as a biomarker and its biological activity.
Fibroblast, Epithelial and Endothelial Cell-Derived Human Cytomegalovirus Strains Display Distinct Neutralizing Antibody Responses and Varying Levels of gH/gL Complexes
Authors: Fornara Chiara , Schultz Eric , Lilleri Daniele , Baldanti Fausto , Ryckman Brent , Gerna Giuseppe
Published: February 2023

In sequential sera from pregnant women with HCMV primary infection (PI), the serum neutralizing activity is higher against virions produced in epithelial and endothelial cells than in fibroblasts. Immunoblotting shows that the pentamer complex/trimer complex (PC/TC) ratio varies according to the producer cell culture type used for the virus preparation to be employed in the neutralizing antibody (NAb) assay, and is lower in fibroblasts and higher in epithelial, and especially endothelial cells. The blocking activity of TC- and PC-specific inhibitors varies according to the PC/TC ratio of virus preparations. The rapid reversion of the virus phenotype following its back passage to the original cell culture (fibroblasts) potentially argues in favor of a producer cell effect on virus phenotype. However, the role of genetic factors cannot be overlooked. In addition to the producer cell type, the PC/TC ratio may differ in single HCMV strains. In conclusion, the NAb activity not only varies with different HCMV strains, but is a dynamic parameter changing according to virus strain, type of target and producer cells, and number of cell culture passages. These findings may have some important implications for the development of both therapeutic antibodies and subunit vaccines.
Crucial Abiotic Stress Regulatory Network of NF-Y Transcription Factor in Plants
Authors: Zhang Han , Liu Shujing , Ren Tianmeng , Niu Mengxue , Liu Xiao , Liu Chao , Wang Houling , Yin Weilun , Xia Xinli
Published: February 2023

Nuclear Factor-Y (NF-Y), composed of three subunits NF-YA, NF-YB and NF-YC, exists in most of the eukaryotes and is relatively conservative in evolution. As compared to animals and fungi, the number of NF-Y subunits has significantly expanded in higher plants. The NF-Y complex regulates the expression of target genes by directly binding the promoter CCAAT box or by physical interaction and mediating the binding of a transcriptional activator or inhibitor. NF-Y plays an important role at various stages of plant growth and development, especially in response to stress, which attracted many researchers to explore. Herein, we have reviewed the structural characteristics and mechanism of function of NF-Y subunits, summarized the latest research on NF-Y involved in the response to abiotic stresses, including drought, salt, nutrient and temperature, and elaborated the critical role of NF-Y in these different abiotic stresses. Based on the summary above, we have prospected the potential research on NF-Y in response to plant abiotic stresses and discussed the difficulties that may be faced in order to provide a reference for the in-depth analysis of the function of NF-Y transcription factors and an in-depth study of plant responses to abiotic stress.
Transcriptomes of Zebrafish in Early Stages of Multiple Viral Invasions Reveal the Role of Sterols in Innate Immune Switch-On
Authors: Ouyang Gang , Yuan Le , Xia Xiao-Qin , Zhang Wanting , Shi Mijuan
Published: February 2023

Although it is widely accepted that in the early stages of virus infection, fish pattern recognition receptors are the first to identify viruses and initiate innate immune responses, this process has never been thoroughly investigated. In this study, we infected larval zebrafish with four different viruses and analyzed whole-fish expression profiles from five groups of fish, including controls, at 10 h after infection. At this early stage of virus infection, 60.28% of the differentially expressed genes displayed the same expression pattern across all viruses, with the majority of immune-related genes downregulated and genes associated with protein synthesis and sterol synthesis upregulated. Furthermore, these protein synthesis- and sterol synthesis-related genes were strongly positively correlated in the expression pattern of the rare key upregulated immune genes, IRF3 and IRF7, which were not positively correlated with any known pattern recognition receptor gene. We hypothesize that viral infection triggered a large amount of protein synthesis that stressed the endoplasmic reticulum and the organism responded to this stress by suppressing the body’s immune system while also mediating an increase in steroids. The increase in sterols then participates the activation of IRF3 and IRF7 and triggers the fish’s innate immunological response to the virus infection.
Mass Spectrometry-Based Untargeted Approaches to Reveal Diagnostic Signatures of Male Infertility in Seminal Plasma: A New Laboratory Perspective for the Clinical Management of Infertility?
Authors: Preianò Mariaimmacolata , Correnti Serena , Butt Tahreem Arshad , Viglietto Giuseppe , Savino Rocco , Terracciano Rosa
Published: February 2023

Male infertility has been recognized as a global health problem. Semen analysis, although considered the golden standard, may not provide a confident male infertility diagnosis alone. Hence, there is the urgent request for an innovative and reliable platform to detect biomarkers of infertility. The rapid expansion of mass spectrometry (MS) technology in the field of the ‘omics’ disciplines, has incredibly proved the great potential of MS-based diagnostic tests to revolutionize the future of pathology, microbiology and laboratory medicine. Despite the increasing success in the microbiology area, MS-biomarkers of male infertility currently remain a proteomic challenge. In order to address this issue, this review encompasses proteomics investigations by untargeted approaches with a special focus on experimental designs and strategies (bottom-up and top-down) for seminal fluid proteome profiling. The studies reported here witness the efforts of the scientific community to address these investigations aimed at the discovery of MS-biomarkers of male infertility. Proteomics untargeted approaches, depending on the study design, might provide a great plethora of biomarkers not only for a male infertility diagnosis, but also to address a new MS-biomarkers classification of infertility subtypes. From the early detection to the evaluation of infertility grade, new MS-derived biomarkers might also predict long-term outcomes and clinical management of infertility.
Hypoxia in Skin Cancer: Molecular Basis and Clinical Implications
Authors: Jeon Sungmi , Jeon Miyeon , Choi Sanga , Yoo Seongkyeong , Park Soohyun , Lee Mingyu , Kim Iljin
Published: February 2023

Skin cancer is one of the most prevalent cancers in the Caucasian population. In the United States, it is estimated that at least one in five people will develop skin cancer in their lifetime, leading to significant morbidity and a healthcare burden. Skin cancer mainly arises from cells in the epidermal layer of the skin, where oxygen is scarce. There are three main types of skin cancer: malignant melanoma, basal cell carcinoma, and squamous cell carcinoma. Accumulating evidence has revealed a critical role for hypoxia in the development and progression of these dermatologic malignancies. In this review, we discuss the role of hypoxia in treating and reconstructing skin cancers. We will summarize the molecular basis of hypoxia signaling pathways in relation to the major genetic variations of skin cancer.
Biceps Tenodesis Better Improves the Shoulder Function Compared with Tenotomy for Long Head of the Biceps Tendon Lesions: A Meta-Analysis of Randomised Controlled Trials
Authors: Zhang Chunsen , Yang Guang , Li Tao , Pang Long , Li Yinghao , Yao Lei , Li Ran , Tang Xin
Published: February 2023

Purpose: Surgical options for long head of the biceps tendon (LHBT) lesions include tenotomy and tenodesis. This study aims to determine the optimal surgical strategy for LHBT lesions with updated evidence from randomised controlled trials (RCTs). Methods: Literature was retrieved from PubMed, Cochrane Library, Embase and Web of Science on 12 January 2022. Randomised controlled trials (RCTs) comparing the clinical outcomes of tenotomy and tenodesis were pooled in the meta-analyses. Results: Ten RCTs with 787 cases met the inclusion criteria, and were included in the meta-analysis. Constant scores (MD, −1.24; p = 0.001), improvement of Constant scores (MD, −1.54; p = 0.04), Simple Shoulder Test (SST) scores (MD, −0.73; p = 0.03) and improvement of SST (p < 0.05) were significantly better in patients with tenodesis. Tenotomy was associated with higher rates of Popeye deformity (OR, 3.34; p < 0.001) and cramping pain (OR, 3.36; p = 0.008]. No significant differences were noticed between tenotomy and tenodesis regarding pain (p = 0.59), American Shoulder and Elbow Surgeons (ASES) score (p = 0.42) and its improvement (p = 0.91), elbow flexion strength (p = 0.38), forearm supination strength (p = 0.68) and range of motion of shoulder external rotation (p = 0.62). Subgroup analyses showed higher Constant scores in all tenodesis types and significantly larger improvement of Constant scores regarding intracuff tenodesis (MD, −5.87; p = 0.001). Conclusions: According to the analyses of RCTs, tenodesis better improves shoulder function in terms of Constant scores and SST scores, and reduces the risk of Popeye deformity and cramping bicipital pain. Intracuff tenodesis might offer the best shoulder function as measured with Constant scores. However, tenotomy and tenodesis provide similar satisfactory results for pain relief, ASES score, biceps strength and shoulder range of motion.
Vaginal-Laparoscopic Repair (VLR) of Primary and Persistent Vesico-Vaginal Fistula: Description of a New Technique and Surgical Outcomes
Authors: Tozzi Roberto , Spagnol Giulia , Marchetti Matteo , Montan Giulia , Saccardi Carlo , Noventa Marco
Published: February 2023

The main aim of our study was to describe the surgical technique and evaluate the feasibility, efficacy and safety of a vaginal-laparoscopic repair (VLR) of iatrogenic vesico-vaginal fistulae (VVF). Between April-2009 and November-2017, we retrospectively reviewed all clinical, radiological and surgical details of surgery for benign or malignant disease and ended up with VVF. All patients were diagnosed by CT urogram, cystogram and clinical test. The surgical technique was standardised and is described here. Eighteen patients developed VVF after hysterectomy, three after caesarean section and three after hysterectomy and pelvic lymphadenectomy. Twenty-two patients had an average 3 (range 1–5) attempts at fistula repair in other hospitals. In one patient, five attempts were made. The mean size of the fistula was 2.4 cm (range 0.7–3.1 cm). A median 8 weeks (6–16) conservative management with Foley catheter failed in all patients. No conversion to laparotomy and no complication occurred at VLR. Median hospitalisation was 1.4 days (range 1–3). The latter confirmed all patients were dry and tested negative at a repeated filling test. At 36 months follow-up, all patients remained dry. In conclusion, VLR successfully repaired VVF in all patients with primary and persistent VVF. The technique was safe and effective.
Alemtuzumab-Related Lymphocyte Subset Dynamics and Disease Activity or Autoimmune Adverse Events: Real-World Evidence
Authors: Signoriello Elisabetta , Lus Giacomo , Saccà Francesco , Puthenparampil Marco , Coppola Cinzia , Di Pietro Andrea , Puoti Gianfranco , Criscuolo Maria , Foschi Matteo , Miele Giuseppina , Abbadessa Gianmarco , Brescia Morra Vincenzo , Gallo Paolo , Bonavita Simona , Sormani Maria , Signori Alessio
Published: February 2023

Background and objectives: alemtuzumab is a monoclonal anti-CD52 antibody acting on B and T cells in highly active multiple sclerosis (MS). We analyzed changes in lymphocyte subsets after alemtuzumab administration in relation to disease activity and autoimmune adverse events. Methods: lymphocyte subset counts were assessed longitudinally using linear mixed models. Subset counts at baseline and during follow-up were correlated with relapse rate, adverse events, or magnetic resonance (MRI) activity. Results: we recruited 150 patients followed for a median of 2.7 years (IQR: 1.9–3.7). Total lymphocytes, CD4, CD8, and CD20 significantly decreased in all patients over 2 years (p < 0.001). Previous treatment with fingolimod increased the risk of disease activity and adverse events (p = 0.029). We found a higher probability of disease reactivation in males and in patients with over three active lesions at baseline. Higher EDSS scores at baseline and longer disease duration predicted the switch to other treatments after alemtuzumab. Discussion and conclusions: Our real-world study supports data from clinical trials in which lymphocyte subsets were not useful for predicting disease activity or autoimmune disease during treatment. The early use of an induction therapy such as alemtuzumab in patients with a lower EDSS score and short history of disease could mitigate the risk of treatment failure.
Relapsed/Refractory Chronic Lymphocytic Leukemia Patients Treated with Fixed Duration Venetoclax-Rituximab: Assessment of Response with Ultrasound, and Relationship with Minimal Residual Disease
Authors: Benedetti Edoardo , Baratè Claudia , Mavilia Fabrizio , Bramanti Emilia , Morganti Riccardo , Guerri Valentina , Cervetti Giulia , Capochiani Enrico , Bertaggia Ilaria , Stella Salvatore Massimo , Traverso Ginevra , Bruno Benedetto , Galimberti Sara
Published: February 2023

A fixed duration of venetoclax-rituximab (VenR) resulted in a significant benefit of both PFS and in the attainment of an undetectable minimal residual disease (uMRD) compared with bendamustine-rituximab in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) patients. The 2018 International Workshop on CLL guidelines, outside the context of clinical trials, suggested ultrasonography (US) as a possible imaging technique to evaluate visceral involvement, and palpation to evaluate superficial lymph nodes (SupLNs). In this real-life study we prospectively enrolled N = 22 patients. Patients were assessed by US, to determine nodal and splenic response in R/R CLL patients treated with a fixed duration VenR. We found an overall response rate, complete remission, partial remission, and stable disease, of 95.4%, 68%, 27.3%, and 4.5%, respectively. Responses were also correlated with risk categories. The time to response, and the time to clearance of the disease in the spleen, in abdominal LN (AbdLNs), and in SupLNs were discussed. Responses were independent from LN size. The correlation between response rate with MRD were also investigated. US allowed to detect a substantial CR rate correlated with uMRD.
Outcome of Kidney Transplants from Viremic and Non-Viremic Hepatitis C Virus Positive Donors into Negative Recipients: Results of the Spanish Registry
Authors: Franco Antonio , Moreso Francesc , Solà-Porta Eulàlia , Beneyto Isabel , Esforzado Núria , Gonzalez-Roncero Francisco , Sancho Asunción , Melilli Edoardo , Ruiz Juan Carlos , Galeano Cristina
Published: February 2023

Historically, donor infection with hepatitis-C virus (HCV) has been a barrier to kidney transplantation. However, in recent years, it has been reported that HCV positive kidney donors transplanted into HCV negative recipients offer acceptable mid-term results. However, acceptance of HCV donors, especially viremic, has not broadened in the clinical practice. This is an observational, multicenter, retrospective study including kidney transplants from HCV positive donors into negative recipients reported to the Spanish group from 2013 to 2021. Recipients from viremic donors received peri-transplant treatment with direct antiviral agents (DAA) for 8–12 weeks. We included 75 recipients from 44 HCV non-viremic donors and 41 from 25 HCV viremic donors. Primary non function, delayed graft function, acute rejection rate, renal function at the end of follow up, and patient and graft survival were not different between groups. Viral replication was not detected in recipients from non-viremic donors. Recipient treatment with DAA started pre-transplant avoids (n = 21) or attenuates (n = 5) viral replication but leads to non-different outcomes to post-transplant treatment with DAA (n = 15). HCV seroconversion was more frequent in recipients from viremic donors (73% vs. 16%, p < 0.001). One recipient of a viremic donor died due to hepatocellular carcinoma at 38 months. Donor HCV viremia seems not to be a risk factor for kidney transplant recipients receiving peri-transplant DAA, but continuous surveillance should be advised.
Early Impact of Laser Vision Correction (LVC) on the Stability and Quality of the Retinal Image
Authors: Smadja David , Erdinest Nir , Wajnsztajn Denise , Weill Yishay , Abulafia Adi , Zadok David , Lavy Itay
Published: February 2023

This retrospective comparative study analyzes the early postoperative impact of laser vision correction for myopia on the optical quality and stability of functional vision using a double-pass aberrometer. Retinal image quality and visual function stability were assessed preoperatively, one and three months after myopic laser in situ keratomileuses (LASIK) and photorefractive keratectomy (PRK) using double-pass aberrometry (HD Analyzer, Visiometrics S.L, Terrassa, Spain). The parameters analyzed included vision break-up time (VBUT), objective scattering index (OSI), modulation transfer function (MTF), and Strehl ratio (SR). The study included 141 eyes of 141 patients, of whom 89 underwent PRK and 52 underwent LASIK. No statistically significant differences were noted between the two techniques in any analyzed parameters at three months postoperatively. However, a significant drop was observed in all parameters one month after PRK. Only the OSI and VBUT remained significantly altered from baseline at the three months follow-up visit, with an increased OSI by 0.14 +/− 0.36 (p < 0.01) and a shortened VBUT by 0.57 +/− 2.3 s (p < 0.01). No correlation was found between the changes in optical and visual quality parameters and age, ablation depth, or postoperative spherical equivalent. The stability and quality of the retinal images were similar between LASIK and PRK at three months postoperatively. However, significant degradation in all parameters was found one month after PRK.
Effects of Acute Hypoxia on Heart Rate Variability in Patients with Pulmonary Vascular Disease
Authors: Meszaros Martina , Schneider Simon , Mayer Laura , Lichtblau Mona , Pengo Martino , Berlier Charlotte , Saxer Stéphanie , Furian Michael , Bloch Konrad , Ulrich Silvia , Schwarz Esther
Published: February 2023

Pulmonary vascular diseases (PVDs), defined as arterial or chronic thromboembolic pulmonary hypertension, are associated with autonomic cardiovascular dysregulation. Resting heart rate variability (HRV) is commonly used to assess autonomic function. Hypoxia is associated with sympathetic overactivation and patients with PVD might be particularly vulnerable to hypoxia-induced autonomic dysregulation. In a randomised crossover trial, 17 stable patients with PVD (resting PaO2 ≥ 7.3 kPa) were exposed to ambient air (FiO2 = 21%) and normobaric hypoxia (FiO2 = 15%) in random order. Indices of resting HRV were derived from two nonoverlapping 5–10-min three-lead electrocardiography segments. We found a significant increase in all time- and frequency-domain HRV measures in response to normobaric hypoxia. There was a significant increase in root mean squared sum difference of RR intervals (RMSSD; 33.49 (27.14) vs. 20.76 (25.19) ms; p < 0.01) and RR50 count divided by the total number of all RR intervals (pRR50; 2.75 (7.81) vs. 2.24 (3.39) ms; p = 0.03) values in normobaric hypoxia compared to ambient air. Both high-frequency (HF; 431.40 (661.56) vs. 183.70 (251.25) ms2; p < 0.01) and low-frequency (LF; 558.60 (746.10) vs. 203.90 (425.63) ms2; p = 0.02) values were significantly higher in normobaric hypoxia compared to normoxia. These results suggest a parasympathetic dominance during acute exposure to normobaric hypoxia in PVD.
Severity and Longitudinal Course of Depression, Anxiety and Post-Traumatic Stress in Paediatric and Young Adult Cancer Patients: A Systematic Review and Meta-Analysis
Authors: Lee Ainsley Ryan Yan Bin , Yau Chun En , Low Chen Ee , Li Jiaqi , Ho Roger C. M. , Ho Cyrus Su Hui
Published: February 2023

Background: A diagnosis of cancer and treatment may constitute a highly traumatic period for paediatric cancer patients (PYACPs). However, no review has comprehensively analysed how the mental health of PYACPs is acutely affected and the longitudinal course. Methods: This systematic review followed PRISMA guidelines. Comprehensive searches of databases were conducted to identify studies of depression, anxiety and post-traumatic stress symptoms in PYACPs. Random effects meta-analyses were used for the primary analysis. Results: From 4898 records, 13 studies were included. Acutely after diagnosis, depressive and anxiety symptoms were significantly elevated in PYACPs. Depressive symptoms only significantly decreased after 12 months (standardised mean difference, SMD = −0.88; 95% CI: −0.92, −0.84). This downward trajectory persisted to 18 months (SMD = −1.862; 95% CI: −1.29, −1.09). Anxiety symptoms similarly only decreased after 12 (SMD = −0.34; 95% CI: −0.42, −0.27) up to 18 months (SMD = −0.49; 95% CI: −0.60, −0.39) after the cancer diagnosis. Post-traumatic stress symptoms showed protracted elevations throughout follow-up. Overall, significant predictors of poorer psychological outcomes included unhealthy family functioning, concomitant depression or anxiety, poor cancer prognosis or experiencing cancer and treatment-related side effects. Conclusions: While depression and anxiety may improve over time with a favourable environment, post-traumatic stress may have a protracted course. Timely identification and psycho-oncological intervention are critical.
Inter- and Intra-Observer Variability and the Effect of Experience in Cine-MRI for Adhesion Detection
Authors: de Wilde Bram , Joosten Frank , Venderink Wulphert , Davidse Mirjam E. J. , Geurts Juliëtte , Kruijt Hanneke , Vermeulen Afke , Martens Bibi , Schyns Maxime V. P. , Huige Josephine C. B. M. , de Boer Myrte C. , Tonino Bart A. R. , Zandvoort Herman J. A. , Lammert Kirsti , Parviainen Helka , Vuorinen Aino-Maija , Syväranta Suvi , Vogels Ruben R. M. , Prins Wiesje , Coppola Andrea , Bossa Nancy , ten Broek Richard P. G. , Huisman Henkjan
Published: February 2023

Cine-MRI for adhesion detection is a promising novel modality that can help the large group of patients developing pain after abdominal surgery. Few studies into its diagnostic accuracy are available, and none address observer variability. This retrospective study explores the inter- and intra-observer variability, diagnostic accuracy, and the effect of experience. A total of 15 observers with a variety of experience reviewed 61 sagittal cine-MRI slices, placing box annotations with a confidence score at locations suspect for adhesions. Five observers reviewed the slices again one year later. Inter- and intra-observer variability are quantified using Fleiss’ (inter) and Cohen’s (intra) κ and percentage agreement. Diagnostic accuracy is quantified with receiver operating characteristic (ROC) analysis based on a consensus standard. Inter-observer Fleiss’ κ values range from 0.04 to 0.34, showing poor to fair agreement. High general and cine-MRI experience led to significantly (p < 0.001) better agreement among observers. The intra-observer results show Cohen’s κ values between 0.37 and 0.53 for all observers, except one with a low κ of −0.11. Group AUC scores lie between 0.66 and 0.72, with individual observers reaching 0.78. This study confirms that cine-MRI can diagnose adhesions, with respect to a radiologist consensus panel and shows that experience improves reading cine-MRI. Observers without specific experience adapt to this modality quickly after a short online tutorial. Observer agreement is fair at best and area under the receiver operating characteristic curve (AUC) scores leave room for improvement. Consistently interpreting this novel modality needs further research, for instance, by developing reporting guidelines or artificial intelligence-based methods.
Clinical Features and Outcomes of Japanese Patients with Giant Cell Arteritis: A Comparison with Takayasu Arteritis
Authors: Yoshida Shuhei , Suzuki Eiji , Sumichika Yuya , Saito Kenji , Matsumoto Haruki , Temmoku Jumpei , Fujita Yuya , Matsuoka Naoki , Asano Tomoyuki , Sato Shuzo , Watanabe Hiroshi , Migita Kiyoshi
Published: February 2023

Background: Giant cell arteritis (GCA) and Takayasu arteritis (TA) are distinct types of large-vessel vasculitis; however, the clinical features of the diseases have some similarities. Limited data are available regarding Japanese patients with GCA and TA. The present study aimed to compare the clinical features and outcomes of Japanese patients with GCA and TA and the effects of large vessel involvement (LVI). Methods: We performed a retrospective cohort study of the patients with GCA (n = 15) and TA (n = 30) who visited our department from April 2012 to June 2022. Signs and symptoms attributed to the disease, treatment, clinical outcomes, and mortality were recorded using a standardized database. Results: The median age of onset was significantly higher in the GCA group at 24 years (range, 16–72 years) in the TA group and 77 years (range, 57–89 years) in the GCA group (p < 0.001). There were no significant differences in survival rates or the cumulative rates of cardiovascular events between the GCA and TA groups. However, relapse-free survival rates were significantly higher in patients with GCA than in patients with TA. Seven of the 15 patients with GCA had large vessel involvement, which did not affect the survival rates. Prednisolone (PSL) doses were significantly decreased after induction therapy in both groups, and the rates of achieving steroid tapering (PSL < 5.0 mg/day) were significantly higher in patients with GCA compared with those in patients with TA. Conclusions: Our study demonstrated no significant difference in the survival rates of Japanese patients with GCA and TA. The relapse-free survival rates were significantly higher in the GCA group than in the TA group. LVI may not be associated with disease relapse or survival rate in Japanese patients with GCA.
A Study on the Barriers to Entrepreneurship in the UAE
Authors: Alnassai Jamal Mohammad Ibrahim Abdulla
Published: February 2023

A variety of factors have an influential impact on how an enterprise develops. This study examined factors that operate as market barriers to entrepreneurship in the United Arab Emirates. These factors are fear of failure, risk aversion, lack of social networking, lack of resources, political instability, and economic instability. A survey-based approach framework was used. This survey recruited 150 participants, including UAE students, business owners, and budding entrepreneurs. Multiple-item survey questionnaires and secondary data were used in the data analysis process to identify and evaluate the barriers preventing people from starting new businesses and becoming entrepreneurs in the United Arab Emirates. According to the research results, fear of failure, risk aversion, and lack of resources in the United Arab Emirates make it difficult for business owners to launch brand new business ventures.
Using and Creating Microclimates for Cork Oak Adaptation to Climate Change
Authors: Vizinho André , Príncipe Adriana , Vasconcelos Ana Cátia , Rebelo Rui , Branquinho Cristina , Penha-Lopes Gil
Published: February 2023

In Mediterranean climate regions, climate change is increasing aridity and contributing to the mortality rate of Quercus suber, reducing the success of reforestation efforts. Using and creating microclimates is a recommended climate adaptation strategy that needs research. Our hypothesis is that planting Q. suber in north-facing slopes and water lines results in a higher survival rate than those that are planted in ridges and south-facing slopes. Secondly, our hypothesis is that existing shrubs (in this case, Cistus ladanifer) can be used to create microclimatic sheltering and increase the survival of Q. suber plantations. In experiment 1, we tested the survival of Q. suber plantations in four different topographic conditions. For that, 80 Q. suber plants were planted over four different topographic conditions, where soil probes were installed to monitor soil moisture and temperature. Two years after, the results show an increased survival rate in the north-facing slope and water line when compared to the ridge area (p = 0.032). In experiment 2, we tested if planting in the shade of rows of C. ladanifer increases the survival rate of Q. suber plantations. For that, 1200 Q. suber plants were planted; 600 in a Montado open area with no shade and 600 under the shade of rows of C. ladanifer shrubs. A total of 17 months after plantation, there was a significantly higher survival rate of the shaded plants (p = 0.027). We conclude that microclimates created by topography and shrubs can have a significant impact on the survival of Q. suber plantations and discuss the situations in which these can apply.
Examining the Spatial Effect of “Smartness” on the Relationship between Agriculture and Regional Development: The Case of Greece
Authors: Koutridi Evagelia , Tsiotas Dimitrios , Christopoulou Olga
Published: February 2023

Digital transformation in farming via smart farming technologies (SFTs) is highly considered to stimulate sustainability in the food market and agriculture, as well as to promote viability in the agricultural sector and the prosperity of rural areas. In Greece, a great number of SFTs were financed through Action 4.1.1, by the EU’s Rural Development Program, supporting agricultural production and promoting sustainable regional development. Within this policy context, this paper aims to examine the transformation level that “smartness” induced in the relationship between agriculture and regional development in Greece. To do so, it builds a multilevel methodological framework thematically describing both “traditional” and smart agriculture in terms of spatial demand, transportation cost, knowledge intensity, and economies of scale, which are theoretically and empirically considered as major pillars related to regional development. The analysis is applied regional data (NUTS 3) in Greece, focusing on the detection of significant spatial and functional changes in the thematic model developed with respect to the proposed methodological framework. Findings provide insights into the effect that the SFTs can have on sustainable regional development, based on the reasoning of relevant background regional economic theories.
Interactions between Differential Object Marking and Definiteness in Standard and Heritage Romanian
Authors: Irimia Monica Alexandrina
Published: February 2023

The observation that not all grammatical realizations in heritage languages can be attributed to transfer from a dominant language has been emphasized in several recent works. This paper provides further arguments in this direction from heritage Romanian. As opposed to standard Romanian, the heritage Romanian data examined here do not exhibit a restriction which blocks overt definiteness on a differentially marked object (DOM), when the latter is unmodified but interpreted as definite. Moreover, in heritage Romanian there appear to be differences between the differential marker and (other) prepositions when it comes to interactions with overt definiteness. It is shown that the preservation of overt definiteness cannot be reduced to transfer; some of the dominant languages at stake, namely Serbian and Russian are determinerless, with nominals being used bare regardless of their syntactic function. The heritage data in turn give support to a theory under which the differential marker must be structurally set aside from (other) prepositions. If the latter spell out a P projection, the differential marker is the spell out of complex internal structure of certain classes of objects, which must project at least a DP. This structural complexity for DOM is transparent in other Romance languages, where definiteness is equally obligatory on the surface, if a definite interpretation is intended. Thus, the DOM-overt definiteness setting in the heritage data follows from predictable paths of language variation.
PET Criteria by Cancer Type from Imaging Interpretation to Treatment Response Assessment: Beyond FDG PET Score
Authors: Dondi Francesco , Lazzarato Achille , Gorica Joana , Guglielmo Priscilla , Borgia Francesca , Filice Rossella , Vento Antonio , Pacella Sara , Camedda Riccardo , Caracciolo Matteo , De Feo Maria Silvia , Mammucci Paolo , Frantellizzi Viviana , Ortolan Naima , Fiasconaro Elisa , Urso Luca , Evangelista Laura , Laudicella Riccardo , Santo Giulia
Published: February 2023

Background: in recent years, the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) has emerged as a reliable diagnostic tool in a wide variety of pathological conditions. This review aims to collect and review PET criteria developed for interpretation and treatment response assessment in cases of non-[18F]fluorodeoxyglucose ([18F]FDG) imaging in oncology. Methods: A wide literature search of the PubMed/MEDLINE, Scopus and Google Scholar databases was made to find relevant published articles about non-[18F]FDG PET response criteria. Results: The comprehensive computer literature search revealed 183 articles. On reviewing the titles and abstracts, 149 articles were excluded because the reported data were not within the field of interest. Finally, 34 articles were selected and retrieved in full-text versions. Conclusions: available criteria are a promising tool for the interpretation of non-FDG PET scans, but also to assess the response to therapy and therefore to predict the prognosis. However, oriented clinical trials are needed to clearly evaluate their impact on patient management.
Maternal Exposure to Cigarette Smoke during Pregnancy and Testicular Cancer in Offspring: A Systematic Review and Meta-Analysis
Authors: Beck Astrid L. , Bräuner Elvira V. , Hauser Russ , Lim Youn-Hee , Uldbjerg Cecilie S. , Juul Anders
Published: February 2023

Background: Maternal exposure to cigarette smoke in pregnancy may play a role in the development of testicular cancer in offspring. An updated and comprehensive systematic review of the available evidence is needed. Objective: To identify and evaluate current evidence on maternal exposure to cigarette smoke during pregnancy and testicular cancer in offspring. Methods: A systematic search of English peer-reviewed original literature in PubMed through a block search approach. Publications were considered if assessing maternal exposure to cigarette smoke and the risk of testicular cancer in offspring. Results: Among the 636 identified records, 14 publications were eligible for review and 10 for meta-analysis. Quality assessment of the publications was conducted. Most included publications were case-control studies (n = 11, 79%), while the remaining were ecological studies (n = 3, 21%). Completeness of reporting was high, but more than half were considered subject to potential bias. The trend synthesis showed that half (n = 7) of the included publications demonstrated a higher risk of testicular cancer in the sons of mothers exposed to cigarette smoke during pregnancy. The meta-analysis generated an overall summary risk estimate of 1.00 (95% CI: 0.88; 1.15) (n = 10 publications), with a lower risk for seminoma (0.79, 95% CI: 0.59; 1.04) and nonseminoma (0.96, 95% CI: 0.74; 1.26) (n = 4 publications). Conclusions: This systematic review did not provide evidence of an association between maternal exposure to cigarette smoke and risk of testicular cancer in offspring. An overall positive trend was suggested, but it had low statistical precision. The methodological limitations across publications encourage further research based on valid exposure data.
Fluorinated Multi-Walled Carbon Nanotubes Coated Separator Mitigates Polysulfide Shuttle in Lithium-Sulfur Batteries
Authors: Salpekar Devashish , Dong Changxin , Oliveira Eliezer F. , Khabashesku Valery N. , Gao Guanhui , Ojha Ved , Vajtai Robert , Galvao Douglas S. , Babu Ganguli , Ajayan Pulickel M.
Published: February 2023

Li-S batteries still suffer from two of the major challenges: polysulfide shuttle and low inherent conductivity of sulfur. Here, we report a facile way to develop a bifunctional separator coated with fluorinated multiwalled carbon nanotubes. Mild fluorination does not affect the inherent graphitic structure of carbon nanotubes as shown by transmission electron microscopy. Fluorinated carbon nanotubes show an improved capacity retention by trapping/repelling lithium polysulfides at the cathode, while simultaneously acting as the “second current collector”. Moreover, reduced charge-transfer resistance and enhanced electrochemical performance at the cathode-separator interface result in a high gravimetric capacity of around 670 mAh g−1 at 4C. Unique chemical interactions between fluorine and carbon at the separator and the polysulfides, studied using DFT calculations, establish a new direction of utilizing highly electronegative fluorine moieties and absorption-based porous carbons for mitigation of polysulfide shuttle in Li-S batteries.
Red-Emitting Dithienothiophene S,S-Dioxide Dyes for Cellular Membrane Staining
Authors: Rzewnicka Aneta , Krysiak Jerzy , Pawłowska Róża , Żurawiński Remigiusz
Published: February 2023

A series of dithienothiophene S,S-dioxide (DTTDO) dyes was designed, synthesized, and investigated for their suitability in fluorescent cell imaging. Synthetized (D-π-A-π-D)-type DTTDO derivatives have molecule lengths close to the thickness of the phospholipid membrane, and they contain on both ends two positively charged or neutral polar groups to increase their solubility in water and to ensure simultaneous interaction with polar groups of the inner and outer part of the cellular membrane. DTTDO derivatives exhibit absorbance and emission maxima in the 517–538 nm and 622–694 nm range, respectively, and a large Stokes shift up to 174 nm. Fluorescence microscopy experiments revealed that these compounds selectively intercalate into cell membranes. Moreover, a cytotoxicity assay conducted on a model human live cells indicates low toxicity of these compounds at the concentrations required for effective staining. With suitable optical properties, low cytotoxicity, and high selectivity against cellular structures, DTTDO derivatives are proven to be attractive dyes for fluorescence-based bioimaging.
The Stressing State Features of a Bottom Frame Structure Revealed from the Shaking Table Strain Data
Authors: Zhang Lingxin , Li Rui , Shen Zijie , Liu Bai , Kong Jianhui , Zhou Guangchun
Published: February 2023

As a classic issue, structural seismic bearing capacity could not be accurately predicted since it was based on a structural ultimate state with inherent uncertainty. This result led to rare research efforts to discover structures’ general and definite working laws from their experimental data. This study is to reveal the seismic working law of a bottom frame structure from its shaking table strain data by applying structural stressing state theory: (1) The tested strains are transformed into generalized strain energy density (GSED) values. (2) The method is proposed to express the stressing state mode and the corresponding characteristic parameter. (3) According to the natural law of quantitative and qualitative change, the Mann–Kendall criterion detects the mutation feature in the evolution of characteristic parameters versus seismic intensity. Moreover, it is verified that the stressing state mode also presents the corresponding mutation feature, which reveals the starting point in the seismic failure process of the bottom frame structure. (4) The Mann–Kendall criterion distinguishes the elastic–plastic branch (EPB) feature in the bottom frame structure’s normal working process, which could be taken as the design reference. This study presents a new theoretical basis to determine the bottom frame structure’s seismic working law and update the design code. Meanwhile, this study opens up the application of seismic strain data in structural analysis.