bluuebunny/crossref_metadata_2025 huggingface dataset:
Sigma-1 Receptor Modulation by Ligands Coordinates Cancer Cell Energy Metabolism
Authors: Oflaz Furkan E. , Koshenov Zhanat , Hirtl Martin , Rost Rene , Malli Roland , Graier Wolfgang F.
Published: May 2022

Sigma-1 receptor (S1R) is an important endoplasmic reticulum chaperone with various functions in health and disease. The purpose of the current work was to elucidate the involvement of S1R in cancer energy metabolism under its basal, activated, and inactivated states. For this, two cancer cell lines that differentially express S1R were treated with S1R agonist, (+)-SKF10047, and antagonist, BD1047. The effects of the agonist and antagonist on cancer energy metabolism were studied using single-cell fluorescence microscopy analysis of real-time ion and metabolite fluxes. Our experiments revealed that S1R activation by agonist increases mitochondrial bioenergetics of cancer cells while decreasing their reliance on aerobic glycolysis. S1R antagonist did not have a major impact on mitochondrial bioenergetics of tested cell lines but increased aerobic glycolysis of S1R expressing cancer cell line. Our findings suggest that S1R plays an important role in cancer energy metabolism and that S1R ligands can serve as tools to modulate it.
Allostery Modulates Interactions between Proteasome Core Particles and Regulatory Particles
Authors: Coffino Philip , Cheng Yifan
Published: May 2022

Allostery—regulation at distant sites is a key concept in biology. The proteasome exhibits multiple forms of allosteric regulation. This regulatory communication can span a distance exceeding 100 Ångstroms and can modulate interactions between the two major proteasome modules: its core particle and regulatory complexes. Allostery can further influence the assembly of the core particle with regulatory particles. In this focused review, known and postulated interactions between these proteasome modules are described. Allostery may explain how cells build and maintain diverse populations of proteasome assemblies and can provide opportunities for therapeutic interventions.
Bio-Inspired Robots and Structures toward Fostering the Modernization of Agriculture
Authors: Kondoyanni Maria , Loukatos Dimitrios , Maraveas Chrysanthos , Drosos Christos , Arvanitis Konstantinos G.
Published: May 2022

Biomimetics is the interdisciplinary cooperation of biology and technology that offers solutions to practical problems by analyzing biological systems and transferring their principles into applications. This review article focused on biomimetic innovations, including bio-inspired soft robots and swarm robots that could serve multiple functions, including the harvesting of fruits, pest control, and crop management. The research demonstrated commercially available biomimetic innovations, including robot bees by Arugga AI Farming and the Robotriks Traction Unit (RTU) precision farming equipment. Additionally, soft robotic systems have made it possible to mitigate the risk of surface bruises, rupture, the crushing destruction of plant tissue, and plastic deformation in the harvesting of fruits with a soft rind such as apples, cherries, pears, stone fruits, kiwifruit, mandarins, cucumbers, peaches, and pome. Even though the smart farming technologies, which were developed to mimic nature, could help prevent climate change and enhance the intensification of agriculture, there are concerns about long-term ecological impact, cost, and their inability to complement natural processes such as pollination. Despite the problems, the market for bio-inspired technologies with potential agricultural applications to modernize farming and solve the abovementioned challenges has increased exponentially. Future research and development should lead to low-cost FEA robotic grippers and FEA-tendon-driven grippers for crop harvesting. In brief, soft robots and swarm robotics have immense potential in agriculture.
Using Carbon Paste Electrode Modified with Ion Imprinted Polymer and MWCNT for Electrochemical Quantification of Methylmercury in Natural Water Samples
Authors: Mesa Ruddy , Khan Sabir , Sotomayor Maria D. P. T. , Picasso Gino
Published: May 2022

Methylmercury (MeHg) is one of the most toxic organic mercury compounds found in the environment. The continuous exposure of human beings to this highly toxic compound may damage their nervous system. The present work reports the development and application of a novel electrochemical sensing technique for the quantification of MeHg using a modified carbon paste electrode with multi-walled carbon nanotubes (MWCNTs) combined with ion imprinted polymer, which is highly selective toward MeHg (CPE/MWCNTs/IIP-MeHg) detection. The ion imprinted polymer was synthesized using 2-mercaptobenzothiazole (MBT), acrylic acid (AA) and MeHg employed as ligand, functional monomer and template ion, respectively, and the synthesized material was characterized by Raman spectroscopy and SEM-EDX. Both the proposed and control sensors were characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The electrochemical measurements were carried out using differential pulse stripping voltammetry (DPSV), and a well-defined anodic peak observed at about +0.138 V (vs. Ag/AgCl) was recorded for MeHg. The application of the CPE/MWCNTs/IIP-MeHg sensor (which increased the charge transfer on the electrode surface) under the DPSV-based electrochemical method (which enhanced the signal intensity) made the detection technique highly sensitive and selective for the quantification of methylmercury. Under optimum experimental conditions, the proposed sensor exhibited a linear response range of 560–610 µg L−1 and a detection limit of 0.538 µg L−1, with acceptable relative error values ≤1% when applied for the detection of MeHg in real water samples.
Music-Enhanced Emotion Identification of Facial Emotions in Autistic Spectrum Disorder Children: A Pilot EEG Study
Authors: Ramirez-Melendez Rafael , Matamoros Elisabet , Hernandez Davinia , Mirabel Julia , Sanchez Elisabet , Escude Nuria
Published: May 2022

The Autistic Spectrum Disorder (ASD) is characterized by a difficulty in expressing and interpreting others’ emotions. In particular, people with ASD have difficulties when interpreting emotions encoded in facial expressions. In the past, music interventions have been shown to improve autistic individuals’ emotional and social skills. The present study describes a pilot study to explore the usefulness of music as a tool for improving autistic children’s emotion recognition in facial expressions. Twenty-five children (mean age = 8.8 y, SD = 1.24) with high-functioning ASD and normal hearing participated in the study consisting of four weekly sessions of 15 min each. Twenty-five participants were randomly divided into an experimental group (N = 14) and a control group (N = 11). During each session, participants in the experimental group were exposed to images of facial expressions for four emotions (happy, sad, angry, and fear). Images were shown in three conditions, with the second condition consisting of music of congruent emotion with the shown images. Participants in the control group were shown only images in all three conditions. For six participants in each group, EEG data were acquired during the sessions, and instantaneous emotional responses (arousal and valence values) were extracted from the EEG data. Inter- and intra-session emotion identification improvement was measured in terms of verbal response accuracy, and EEG response differences were analyzed. A comparison of the verbal responses of the experimental group pre- and post-intervention showed a significant (p = 0.001) average improvement in emotion identification accuracy responses of 26% (SD = 3.4). Furthermore, emotional responses of the experimental group at the end of the study showed a higher correlation with the emotional stimuli being presented, compared with their emotional responses at the beginning of the study. No similar verbal responses improvement or EEG-stimuli correlation was found in the control group. These results seem to indicate that music can be used to improve both emotion identification in facial expressions and emotion induction through facial stimuli in children with high-functioning ASD.
Characterization of Ex Vivo and In Vitro Wnt Transcriptome Induced by Spinal Cord Injury in Rat Microglial Cells
Authors: González-Fernández Carlos , González Pau , González-Pérez Francisco , Rodríguez Francisco Javier
Published: May 2022

It is well known that inflammation is crucial in the onset and progression of neurodegenerative diseases and traumatic central nervous system (CNS) injuries, and that microglia and monocyte-derived macrophages (MDMs) play a pivotal role in neuroinflammation. Therefore, the exploration of molecular signaling pathways that are involved in the microglia/macrophage response might help us to shed light on their eventual therapeutic modulation. Interestingly, there is growing evidence showing that the Wnt family of proteins is involved in different neuropathologies that are characterized by a dysregulated neuroinflammatory response, including spinal cord injury (SCI). Here, we aimed to validate a methodology with competence to assess the physiologically relevant Wnt expression patterns of active microglia and MDMs in a rat model of SCI. For that purpose, we have selected and adapted an in vitro system of primary microglia culture that were stimulated with a lesioned spinal cord extract (SCE), together with an ex vivo protocol of flow cytometry sorting of rat microglia/MDMs at different time-points after contusive SCI. Our study demonstrates that the expression profile of Wnt-related genes in microglia/MDM cells exhibit important differences between these particular scenarios which would be in line with previous studies where similar discrepancies have been described for other molecules. Moreover, our results provide for a first experimental report of the Wnt transcriptome in rat microglia and MDMs after SCI which, together with the research platform that was used in the study, and considering its limitations, we expect might contribute to foster the research on Wnt-driven immunomodulatory therapies.
Recognition of Basic Emotions with and without the Use of Emotional Vocabulary by Adolescents with Down Syndrome
Authors: Pochon Régis , Touchet Claire , Ibernon Laure
Published: May 2022

Background: Children with Down syndrome (DS) often experience behavioral and emotional issues that complicate their socialization process and may lead to psychopathological disorders. These problems may be related to deficits affecting emotional knowledge, particularly emotional vocabulary. Because emotional vocabulary makes it easier for typically developing children to identify emotions, a deficit affecting it in DS could be problematic. Methods: Twenty-eight adolescents with DS matched with typically developing (TD) children for their score on the Benton Facial Recognition Test were asked to recognize six emotional expressions presented in the form of filmed sequences, based on (1) nonverbal cues such as prosody, and (2) an emotional label. Results: The adolescents with DS recognized the six basic emotional expressions at a level comparable to that of the TD children in both conditions (with and without emotional vocabulary), but the facilitating effect of vocabulary was lower in that group. Conclusions: This study does not show a deficit affecting emotion recognition in DS, but it emphasizes the importance of early acquisition of emotional knowledge in this syndrome. Regular and varied use of internal state words should be encouraged in familial interactions, and education should include specifically adapted social and emotional learning programs.
Trust in Institutions, Not in Political Leaders, Determines Compliance in COVID-19 Prevention Measures within Societies across the Globe
Authors: Badman Ryan P. , Wang Ace X. , Skrodzki Martin , Cho Heng-Chin , Aguilar-Lleyda David , Shiono Naoko , Yoo Seng Bum Michael , Chiang Yen-Sheng , Akaishi Rei
Published: May 2022

A core assumption often heard in public health discourse is that increasing trust in national political leaders is essential for securing public health compliance during crises such as the COVID-19 pandemic (2019–ongoing). However, studies of national government trust are typically too coarse-grained to differentiate between trust in institutions versus more interpersonal trust in political leaders. Here, we present multiscale trust measurements for twelve countries and territories across the West, Oceania and East Asia. These trust results were used to identify which specific domains of government and social trust were most crucial for securing public health compliance (frequency of mask wearing and social distancing) and understanding the reasons for following health measures (belief in effectiveness of public health measures). Through the use of linear regression and structural equation modeling, our cross-cultural survey-based analysis (N = 3369 subjects) revealed that higher trust in national and local public health institutions was a universally consistent predictor of public health compliance, while trust in national political leaders was not predictive of compliance across cultures and geographical regions. Institutional trust was mediated by multiple types of transparency, including providing rationale, securing public feedback, and honestly expressing uncertainty. These results highlight the importance of distinguishing between components of government trust, to better understand which entities the public gives the most attention to during crises.
Shear Capacity Stochasticity of Simply Supported and Symmetrically Loaded Reinforced Concrete Beams
Authors: Chen Hui , Yi Wei-Jian , Zhou Ke-Jing
Published: May 2022

For shear tests of reinforced concrete (RC) beams, a simply supported and symmetrical loading system is usually applied. In deterministic analysis, shear capacities of the paired shear spans of such beams are the same. However, considering the randomness of concrete strength, geometric dimension, and other factors, shear failure often occurs in the weaker one of the paired shear spans of a beam rather than occurring in the two shear spans simultaneously. Therefore, from the perspective of probability theory, the shear capacities of the paired shear spans of such simply supported and symmetrically loaded beams can be regarded as two random variables with the same distribution. The beam shear capacity, which is the minimum of the two random variables, is also a random variable. Hence, probabilistic differences exist between the shear capacities of shear spans and beams. In this paper, the transformation relationship between the stochasticities of shear span shear capacity and beam shear capacity is theoretically derived. By taking the RC beams without web reinforcement as an example, the shear capacity stochasticities of shear spans and beams, which are valuable for reliability-based design codes, are quantitatively analyzed based on three shear strength models in design codes and a reliable experimental database. Their probabilistic differences are identified and verified to have an impact on the model calibration in the reliability analysis. The results also show that there are obvious differences in the shear capacity stochasticities obtained by different models. It indicates that to obtain the real stochasticity of the shear capacity, it is not enough to consider the model uncertainty merely but to minimize it. Therefore, models based on a solid understanding of the shear mechanisms are urgently needed for practical design.
Urban Seismic Risk Assessment and Damage Estimation: Case of Rif Buildings (North of Morocco)
Authors: Cherif Seif-Eddine , Chaaraoui Aboubakr , Chourak Mimoun , Oualid Mghazli Mohamed , EL Omari Abdelhay , Ferreira Tiago Miguel
Published: May 2022

The interest in assessing seismic risk in earthquake-prone regions in Morocco has been increasing over recent decades, to a large extent due to the substantial amount of damage imposed by recent events and because the population in these regions has grown significantly. In this context, the present study is aimed to contribute to the understanding of seismic risk in the urban areas of the Rif region, one of the most seismically active zones of Morocco, through the development and analysis of 36 building models representative of this area. Two earthquake scenarios were considered for the assessment of the seismic hazard, based on the national seismic code and the European code adapted to local seismic parameters. The performance points, determined following generated response and capacity spectra, made it possible to establish damage probability matrices. Obtained results corroborate those of previous reports, confirming that the damage is more significant in Imzouren due to the nature of the soil. It has also been shown that the credibility of the response spectra drawn from the national code is questioned, given the extreme damage estimated. The adapted European spectrum proved to be a more reliable probabilistic earthquake scenario for damage estimation.
Dyslipidemia in Children Treated with a BRAF Inhibitor for Low-Grade Gliomas: A New Side Effect?
Authors: Crocco Marco , Verrico Antonio , Milanaccio Claudia , Piccolo Gianluca , De Marco Patrizia , Gaggero Gabriele , Iurilli Valentina , Di Profio Sonia , Malerba Federica , Panciroli Marta , Giordano Paolo , Calevo Maria Grazia , Casalini Emilio , Di Iorgi Natascia , Garrè Maria Luisa
Published: May 2022

BRAF inhibitors, in recent years, have played a central role in the disease control of unresectable BRAF-mutated pediatric low-grade gliomas (LGGs). The aim of the study was to investigate the acute and long-term effects of vemurafenib on the lipid metabolism in children treated for an LGG. In our cohort, children treated with vemurafenib (n = 6) exhibited alterations in lipid metabolism a few weeks after starting, as was demonstrated after 1 month (n = 4) by the high plasma levels of the total cholesterol (TC = 221.5 ± 42.1 mg/dL), triglycerides (TG = 107.8 ± 44.4 mg/dL), and low-density lipoprotein (LDL = 139.5 ± 51.5 mg/dL). Despite dietary recommendations, the dyslipidemia persisted over time. The mean lipid levels of the TC (222.3 ± 34.7 mg/dL), TG (134.8 ± 83.6 mg/dL), and LDL (139.8 ± 46.9 mg/dL) were confirmed abnormal at the last follow-up (45 ± 27 months, n = 6). Vemurafenib could be associated with an increased risk of dyslipidemia. An accurate screening strategy in new clinical trials, and a multidisciplinary team, are required for the optimal management of unexpected adverse events, including dyslipidemia.
Surgical Treatment of Bone Sarcoma
Authors: Bläsius Felix , Delbrück Heide , Hildebrand Frank , Hofmann Ulf Krister
Published: May 2022

Bone sarcomas are rare primary malignant mesenchymal bone tumors. The three main entities are osteosarcoma, chondrosarcoma, and Ewing sarcoma. While prognosis has improved for affected patients over the past decades, bone sarcomas are still critical conditions that require an interdisciplinary diagnostic and therapeutic approach. While radiotherapy plays a role especially in Ewing sarcoma and chemotherapy in Ewing sarcoma and osteosarcoma, surgery remains the main pillar of treatment in all three entities. After complete tumor resection, the created bone defects need to be reconstructed. Possible strategies are implantation of allografts or autografts including vascularized bone grafts (e.g., of the fibula). Around the knee joint, rotationplasty can be performed or, as an alternative, the implantation of (expandable) megaprostheses can be performed. Challenges still associated with the implantation of foreign materials are aseptic loosening and infection. Future improvements may come with advances in 3D printing of individualized resection blades/implants, thus also securing safe tumor resection margins while at the same time shortening the required surgical time. Faster osseointegration and lower infection rates may possibly be achieved through more elaborate implant surface structures.
Exploring Real World Outcomes with Nivolumab Plus Ipilimumab in Patients with Metastatic Extra-Pulmonary Neuroendocrine Carcinoma (EP-NEC)
Authors: Mohamed Amr , Vijayvergia Namrata , Kurian Matthew , Liu Lisa , Fu Pingfu , Das Satya
Published: May 2022

Background: Dual utilization of the immune checkpoint inhibitors (ICPIs) nivolumab plus ipilimumab has demonstrated clinical promise in the treatment of patients with refractory high-grade neuroendocrine neo-plasms (NENs) in phase II clinical trials (DART SWOG 1609 and CA209), while single agent ICPIs have largely been ineffective for these types of tumors. While both trials demonstrated promising results in high grade NENs, there was no adequate description of the association between tumor differentiation (high-grade well-differentiated neuroendocrine tumor vs poorly-differentiated extra-pulmonary neuroendocrine carcinoma (EP-NEC) and ICPI outcomes in the DART SWOG 1609 trial. Our study reports on the effectiveness and toxicity profile of dual ICPIs in a real world second-line EP-NEC patient population. Methods: Data on metastatic EP-NEC patients, treated with either ICPIs (single and dual ICPIs) or chemo-therapy in the second-line setting, were retrieved from databases of three comprehensive cancer centers. Associations between treatment characteristics and outcomes, including progression-free survival (PFS) and overall survival (OS), were evaluated. Results: From 2007 to 2020, we identified 70 patients with metastatic EP-NEC (predominantly of gastro-enteropancreatic origin), of whom 42 patients (23 males, 19 females, median age 62 years old) were eligible for the final analysis. All patients were refractory to platinum etoposide doublet chemotherapy in the first-line setting. The median PFS for patients who received dual ICPIs (11 patients), single agent ICPI (8 patients), and cytotoxic chemotherapy (23 patients) was 258 days, 56.5 days, and 47 days, respectively (p = 0.0001). Median overall survival (OS) for those groups was not reached (NR), 18.7 months, and 10.5 months, respectively (p = 0.004). There were no significant differences in treatment outcomes in patients according to tumor mismatch repair (MMR) or tumor mutational burden (TMB) status. Grade 3–4 adverse events (AEs) were reported in 11.1% of the patients who received dual ICPIs; however, none of these AEs led to permanent treatment discontinuation. Conclusions: In the second-line setting, patients with EP-NECs treated with dual ICPIs (nivolumab plus ipilimumab) experienced improved PFS and OS compared to patients treated with single agent ICPI or cytotoxic chemotherapy. These results echo some of the current evidence for ICPIs in grade 3 NENs and need to be validated in future prospective studies.
Current Status and Future Perspective on the Management of Lymph Node-Positive Prostate Cancer after Radical Prostatectomy
Authors: Shiota Masaki , Blas Leandro , Eto Masatoshi
Published: May 2022

Pathological lymph node involvement (pN1) after a pelvic lymph node dissection represents one of the most unfavorable prognostic factors for disease recurrence and cancer-specific mortality in prostate cancer. However, optimal management for pN1 patients remains unclear. Thus, the guideline from the European Association of Urology recommends discussing three following management options with pN1 patients after an extended pelvic lymph node dissection, based on nodal involvement characteristics: (i) offer adjuvant androgen-deprivation therapy, (ii) offer adjuvant androgen-deprivation therapy with additional radiotherapy and (iii) offer observation (expectant management) to a patient with ≤2 nodes and a prostate-specific antigen <0.1 ng/mL. Treatment intensification may reduce risks of recurrence and cancer-specific mortality, but it may increase adverse events and impair quality of life. Few randomized control trials for pN1 are under investigation. In addition, there are limited reports on the quality of life and patient-reported outcomes in patients with pN1. Therefore, more research is needed to establish an optimal therapeutic strategy for patients with pN1. This review summarizes current evidence on the treatments available for men with pN1, summarizes randomized control trials that included pN1 prostate cancer, and discusses future perspectives.
Use of the Fractal Dimension to Differentiate Epithelium and Connective Tissue in Oral Leukoplakias
Authors: Guerrero-Sánchez Yolanda , Gómez García Francisco , Chamorro-Petronacci Cintia M. , Suárez-Peñaranda José M. , Pérez-Sayáns Mario
Published: May 2022

Background: Oral leukoplakia (OL) is considered one of the most common potentially malignant oral disorders (OPMD), with a verified increased risk of developing oral cancer. The identification of the dysplasia grade (low–high) is the only consolidated factor used to evaluate this risk. The objective of this study was to verify the role of the fractal dimension (FD) in assessing this dysplasia. Methods: To begin, 29 OL and 10 normal oral mucosa (NOM) biopsies were retrieved for FD analysis of the epithelial (dime) and the connective (dimc) tissue. Results: In the OL group, the median value of dime is higher (1.67, IQR = 0.12) than for the NOM group (1.56, IQR = 0.08), with statistically significant differences (Wilcoxon test, p = 0.0031). There were no differences in relation to dimc. Significant differences were observed between the non-dysplasia vs. high-grade (p = 0.0156) and low-grade vs. high-grade (p = 0.0049) groups. No significant differences were identified in relation to dimc for the different degrees of dysplasia. For a cut-off point of 1.44 of dime, a specificity of 96.6% was obtained, a sensitivity of 100%, and an AUC = 0.819 (p = 0.003). Conclusions: FD at the level of the epithelium may be used as a diagnostic tool in OL.
Acute Impact of Cancer Treatment on Head and Neck Cancer Patients: FIT4TREATMENT
Authors: Leão Inês , Garcia Catarina , Antunes Pedro , Campolargo Ana , Dias Isabel , Coimbra Edite , Oliveira Pedro , Zenha Horácio , Costa Horácio , Capela Andreia , Viamonte Sofia , Alves Alberto J. , Joaquim Ana
Published: May 2022

Head and neck cancer (HNC) treatment’s toxicities impact several health domains. Exercise training (ET) may be beneficial. This prospective observational study (NCT04996147) aimed to analyse the acute impact of HNC curative multimodal treatment on health-related quality of life (HRQoL), nutritional status, physical and cognitive functions, and ET preferences. Eighteen patients with stage III/IV HNC were evaluated at baseline (T0), and 10 patients were evaluated at the end of treatment (T1), 7 of them after radical chemoradiotherapy (rCRT). At T0, the majority referred a good HRQoL on the EORTC QLQ-C30 questionnaire (median score: 70.8), were moderately malnourished or at risk of malnutrition (78%), recognized the benefits of an ET program, and were willing to participate (78%). After rCRT, there was worsening in HRQoL (75 vs. 50 score, p = 0.014), dysphagia severity (Eating Assessment Tool: 7 vs. 31, p = 0.027; Functional Oral Intake Scale: 6 vs. 4, p = 0.041), handgrip strength (dominant: 40.9 vs. 35.8 kgf, p = 0.027; nondominant: 37.2 vs. 33.9 kgf, p = 0.043), and nutritional status (Patient-Generated Subjective Global Assessment: 7 vs. 18, p = 0.028). HNC patients subjected to radical treatment represent a vulnerable population that might benefit from multimodal supportive care strategies including an ET program.
Evaluation of the Cell Block Method Using Overnight-Stored Bile for Malignant Biliary Stricture Diagnosis
Authors: Okuno Mitsuru , Mukai Tsuyoshi , Iwata Keisuke , Watanabe Naoki , Tanaka Takuji , Iwasa Taisei , Shimojo Kota , Ohashi Yosuke , Takagi Akihiro , Ito Yuki , Tezuka Ryuichi , Iwata Shota , Iwasa Yuhei , Kochi Takahiro , Ogiso Tomio , Hayashi Hideki , Sugiyama Akihiko , Nishigaki Youichi , Tomita Eiichi
Published: May 2022

The specimen collection and subsequent pathological diagnosis of malignant biliary stricture (MBS) are difficult. This study aimed to determine whether the cell block (CB) method using overnight-stored bile is useful in the diagnosis of MBS. This trial was a single-arm prospective study involving a total of 59 patients with suspected MBS. The primary endpoint was cancer detectability and accuracy using the CB method, and a comparison with the detectability and accuracy achieved with bile cytology was made. The immunohistochemical sensitivity for maspin and p53 was also investigated in the CB and surgical specimens. We were able to collect bile from all 59 patients, and 45 of these patients were clinically diagnosed with MBS. The cancer detectability using the CB method (62.2%) was significantly higher than that using cytology (37.8%) (p = 0.0344). When CB was combined with biopsy, the rates of cancer detectability (75.6%) and accuracy (81.4%) increased. In eight patients who received surgical therapy, maspin- and p53-immunohistochemistry was applied to the surgical and CB specimens, and cancer cells in both specimens showed positive cytoplasmic and nuclear staining for maspin and nuclear staining for p53. The CB method is, thus, useful for detecting malignancy (UMIN000034707).
Comparison of Proclarix, PSA Density and MRI-ERSPC Risk Calculator to Select Patients for Prostate Biopsy after mpMRI
Authors: Campistol Miriam , Morote Juan , Triquell Marina , Regis Lucas , Celma Ana , de Torres Inés , Semidey María E. , Mast Richard , Santamaría Anna , Planas Jacques , Trilla Enrique
Published: May 2022

Tools to properly select candidates for prostate biopsy after magnetic resonance imaging (MRI) have usually been analyzed in overall populations with suspected prostate cancer (PCa). However, the performance of these tools can change regarding the Prostate Imaging-Reporting and Data System (PI-RADS) categories due to the different incidence of clinically significant PCa (csPCa). The objective of the study was to analyze PSA density (PSAD), MRI-ERSPC risk calculator (RC), and Proclarix to properly select candidates for prostate biopsy regarding PI-RADS categories. We performed a head-to-head analysis of 567 men with suspected PCa, PSA > 3 ng/mL and/or abnormal rectal examination, in whom two to four core transrectal ultrasound (TRUS) guided biopsies to PI-RADS ≥ three lesions and/or 12-core TRUS systematic biopsies were performed after 3-tesla mpMRI between January 2018 and March 2020 in one academic institution. The overall detection of csPCa was 40.9% (6% in PI-RADS < 3, 14.8% in PI-RADS 3, 55.3% in PI-RADS 4, and 88.9% in PI-RADS 5). MRI-ERSPC model exhibited a net benefit over PSAD and Proclarix in the overall population. Proclarix outperformed PSAD and MRI-ERSPC RC in PI-RADS ≤ 3. PSAD outperformed MRI-ESRPC RC and Proclarix in PI-RADS > 3, although none of them exhibited 100% sensitivity for csPCa in this setting. Therefore, tools to properly select candidates for prostate biopsy after MRI must be analyzed regarding the PI-RADS categories. While MRI-ERSPC RC outperformed PSAD and Proclarix in the overall population, Proclarix outperformed in PI-RADS ≤ 3, and no tool guaranteed 100% detection of csPCa in PI-RADS 4 and 5.
Combinatorial Therapy of Cancer: Possible Advantages of Involving Modulators of Ionic Mechanisms
Authors: Djamgoz Mustafa B. A.
Published: May 2022

Cancer is a global health problem that 1 in 2–3 people can expect to experience during their lifetime. Several different modalities exist for cancer management, but all of these suffer from significant shortcomings in both diagnosis and therapy. Apart from developing completely new therapies, a viable way forward is to improve the efficacy of the existing modalities. One way is to combine these with each other or with other complementary approaches. An emerging latter approach is derived from ionic mechanisms, mainly ion channels and exchangers. We evaluate the evidence for this systematically for the main treatment methods: surgery, chemotherapy, radiotherapy and targeted therapies (including monoclonal antibodies, steroid hormones, tyrosine kinase inhibitors and immunotherapy). In surgery, the possible systemic use of local anesthetics to suppress subsequent relapse is still being discussed. For all the other methods, there is significant positive evidence for several cancers and a range of modulators of ionic mechanisms. This applies also to some of the undesirable side effects of the treatments. In chemotherapy, for example, there is evidence for co-treatment with modulators of the potassium channel (Kv11.1), pH regulation (sodium–hydrogen exchanger) and Na+-K+-ATPase (digoxin). Voltage-gated sodium channels, shown previously to promote metastasis, appear to be particularly useful for co-targeting with inhibitors of tyrosine kinases, especially epidermal growth factor. It is concluded that combining current orthodox treatment modalities with modulators of ionic mechanisms can produce beneficial effects including (i) making the treatment more effective, e.g., by lowering doses; (ii) avoiding the onset of resistance to therapy; (iii) reducing undesirable side effects. However, in many cases, prospective clinical trials are needed to put the findings firmly into clinical context.
Use of Glycoproteins—Prostate-Specific Membrane Antigen and Galectin-3 as Primary Tumor Markers and Therapeutic Targets in the Management of Metastatic Prostate Cancer
Authors: Sharma Satish , Cwiklinski Katherine , Sykes Donald E. , Mahajan Supriya D. , Chevli Kent , Schwartz Stanley A. , Aalinkeel Ravikumar
Published: May 2022

Galectins and prostate specific membrane antigen (PSMA) are glycoproteins that are functionally implicated in prostate cancer (CaP). We undertook this study to analyze the “PSMA-galectin pattern” of the human CaP microenvironment with the overarching goal of selecting novel-molecular targets for prognostic and therapeutic purposes. We examined CaP cells and biopsy samples representing different stages of the disease and found that PSMA, Gal-1, Gal-3, and Gal-8 are the most abundantly expressed glycoproteins. In contrast, other galectins such as Gal-2, 4–7, 9–13, were uniformly expressed at lower levels across all cell lines. However, biopsy samples showed markedly higher expression of PSMA, Gal-1 and Gal-3. Independently PSA and Gleason score at diagnosis correlated with the expression of PSMA, Gal-3. Additionally, the combined index of PSMA and Gal-3 expression positively correlated with Gleason score and was a better predictor of tumor aggressiveness. Together, our results recognize a tightly regulated “PSMA-galectin- pattern” that accompanies disease in CaP and highlight a major role for the combined PSMA and Gal-3 inhibitors along with standard chemotherapy for prostate cancer treatment. Inhibitor combination studies show enzalutamide (ENZ), 2-phosphonomethyl pentanedioic acid (2-PMPA), and GB1107 as highly cytotoxic for LNCaP and LNCaP-KD cells, while Docetaxel (DOC) + GB1107 show greater efficacy in PC-3 cells. Overall, 2-PMPA and GB1107 demonstrate synergistic cytotoxic effects with ENZ and DOC in various CaP cell lines.
The Potential of AR Solutions for Behavioral Learning: A Scoping Review
Authors: Tosto Crispino , Matin Farzin , Seta Luciano , Chiazzese Giuseppe , Chifari Antonella , Arrigo Marco , Taibi Davide , Farella Mariella , Mangina Eleni
Published: May 2022

In recent years, educational researchers and practitioners have become increasingly interested in new technologies for teaching and learning, including augmented reality (AR). The literature has already highlighted the benefit of AR in enhancing learners’ outcomes in natural sciences, with a limited number of studies exploring the support of AR in social sciences. Specifically, there have been a number of systematic and scoping reviews in the AR field, but no peer-reviewed review studies on the contribution of AR within interventions aimed at teaching or training behavioral skills have been published to date. In addition, most AR research focuses on technological or development issues. However, limited studies have explored how technology affects social experiences and, in particular, the impact of using AR on social behavior. To address these research gaps, a scoping review was conducted to identify and analyze studies on the use of AR within interventions to teach behavioral skills. These studies were conducted across several intervention settings. In addition to this research question, the review reports an investigation of the literature regarding the impact of AR technology on social behavior. The state of the art of AR solutions designed for interventions in behavioral teaching and learning is presented, with an emphasis on educational and clinical settings. Moreover, some relevant dimensions of the impact of AR on social behavior are discussed in more detail. Limitations of the reviewed AR solutions and implications for future research and development efforts are finally discussed.
Predicting the Category and the Length of Punishment in Indonesian Courts Based on Previous Court Decision Documents
Authors: Nuranti Eka Qadri , Yulianti Evi , Husin Husna Sarirah
Published: May 2022

Among the sources of legal considerations are judges’ previous decisions regarding similar cases that are archived in court decision documents. However, due to the increasing number of court decision documents, it is difficult to find relevant information, such as the category and the length of punishment for similar legal cases. This study presents predictions of first-level judicial decisions by utilizing a collection of Indonesian court decision documents. We propose using multi-level learning, namely, CNN+attention, using decision document sections as features to predict the category and the length of punishment in Indonesian courts. Our results demonstrate that the decision document sections that strongly affected the accuracy of the prediction model were prosecution history, facts, legal facts, and legal considerations. The prediction of the punishment category shows that the CNN+attention model achieved better accuracy than other deep learning models, such as CNN, LSTM, BiLSTM, LSTM+attention, and BiLSTM+attention, by up to 28.18%. The superiority of the CNN+attention model is also shown to predict the punishment length, with the best result being achieved using the ‘year’ time unit.
Release Planning Patterns for the Automotive Domain
Authors: Marner Kristina , Wagner Stefan , Ruhe Guenther
Published: May 2022

Context: Today’s vehicle development is focusing more and more on handling the vast amount of software and hardware inside the vehicle. The resulting planning and development of the software especially confronts original equipment manufacturers (OEMs) with major challenges that have to be mastered. This makes effective and efficient release planning that provides the development scope in the required quality even more important. In addition, the OEMs have to deal with boundary conditions given by the OEM itself and the standards as well as legislation the software and hardware have to conform to. Release planning is a key activity for successfully developing vehicles. Objective: The aim of this work is to introduce release planning patterns to simplify the release planning of software and hardware installed in a vehicle. Method: We followed a pattern identification process that was conducted at Dr. Ing. h. c. F. Porsche AG. Results: We introduce eight release planning patterns, which both address the fixed boundary conditions and structure the actual planning content of a release plan. The patterns address an automotive context and have been developed from a hardware and software point of view based on two examples from the case company. Conclusions: The presented patterns address recurring problems in an automotive context and are based on real life examples. The gathered knowledge can be used for further application in practice and related domains.
Public Health Resources, Religion, and Freedom as Predictors of COVID-19 Vaccination Rates: A Global Study of 89 Countries
Authors: Omidvar Tehrani Shadi , Perkins Douglas D.
Published: May 2022

The COVID-19 global pandemic necessitated adequate compliance to safe and effective vaccinations developed against the disease. Vaccination reduces high infection, morbidity, and mortality rates, develops herd immunity, and alleviates overburdened healthcare systems and massive economic costs. COVID-19 also raised awareness about the importance of robust health systems, notably public health competence and the number and training of community health workers. Using the World Health Organization, Global Development of Applied Community Studies project, and other available cross-sectional secondary data on 89 countries, we found that the strength of community health training and research (CHTR), the importance of religion, and freedom score (political rights, civil liberties) are associated with COVID-19 full-vaccination rate. Significant bivariate correlations included per-capita-GDP, number of nurses, per-capita health spending, aged population, noncommunicable disease rate, life satisfaction, government response stringency, nonviolent activism, education, and strength of community development, urban planning, and liberation theology fields. Our assessment of CHTR contribution to the COVID-19 response revealed a great resource for effectively targeting vaccine-hesitant individuals and increasing vaccination rates. The results suggest that to motivate vaccine adherence countries need adequate community health workforce training and research, a population not hesitant to adhere to public health measures based on religion, and societal-level freedoms.
Phylogeography and Population History of Eleutharrhena macrocarpa (Tiliacoreae, Menispermaceae) in Southeast Asia’s Most Northerly Rainforests
Authors: Song Shijie , Shen Jianyong , Zhou Shishun , Guo Xianming , Zhao Jinchao , Shi Xinghui , Yu Zhiyong , Gong Qiangbang , You Shaohua , Landrein Sven
Published: May 2022

The diversification of Tiliacoreae and the speciation of Eleutharrhena are closely linked to Southeast Asia’s most northerly rainforests which originate from the Himalayan uplift. Migration routes across biogeographical zones within the Asian clade, including those of Eleutharrhena, Pycnarrhena, and Macrococculus, and their population structures are still unexplored. We combine endocarp morphology, phylogenetic analyses, divergence time estimation, ancestral area reconstruction, as well as SCoT method to reconstruct the past diversification of Eleutharrhena macrocarpa and to understand their current distribution, rarity, and evolutionary distinctiveness. The disjunct, monospecific, and geographically restricted genera Eleutharrhena and Macrococculus both have a dry aril, a unique feature in Menispermaceae endocarps that further confirms their close relationship. Pycnarrhena and Eleutharrhena appeared during the end of the Oligocene c. 23.10 million years ago (Mya) in Indochina. Eleutharrhena speciation may be linked to climate change during this time, when humid forests became restricted to the northern range due to the Himalayan uplift. Differentiation across the Thai–Burmese range could have contributed to the isolation of the Dehong populations during the Miocene c. 15.88 Mya, when exchange between India and continental Asia ceased. Dispersal to the Lanping–Simao block and further differentiation in southeastern and southern Yunnan occurred during the Miocene, c. 6.82 Mya. The specific habitat requirements that led to the biogeographic patterns observed in E. macrocarpa contributed to a low genetic diversity overall. Population 1 from Dehong, 16 from Pu’er, and 20 from Honghe on the East of the Hua line have a higher genetic diversity and differentiation; therefore, we suggest that their conservation be prioritized.
Importance of Mesohabitat for Nest-Site Selection in Breeding Eagle Owls (Bubo bubo): A Multi-Scale Model
Authors: Hadad Ezra , Malkinson Dan , Yosef Reuven , Weil Gilad , Charter Motti
Published: May 2022

Apex predators make excellent bioindicators of habitat quality and anthropogenic changes. Eagle owls (Bubo bubo) are such apex and keystone predators, who show preferential nest-site selection, usually away from human activities and habitation. However, Israel is a small country with a burgeoning human population. Hence, in order to understand the habitat requirements of eagle owls in central Israel, we conducted a multi-scale model analysis on their existing nest sites between 2006 and 2010. We identified 203 successful breeding attempts at 73 different sites. Our data suggested that the breeding population of the eagle owls was limited by the availability of quality nest locations, i.e., quarries, and caves. The probability of an eagle pair breeding increased with the presence of both quarries and caves, but was not related to mesohabitat properties. In addition, eagle owl breeding densities were positively related to the number of nest localities and to the planted woodlands. Furthermore, we found that eagle owls successfully raised their young regardless of the surrounding mesohabitat and sought the presence of other potential nest sites in the vicinity of the active nest sites, most likely due to the owls’ opportunistic and generalist hunting behavior, which facilitated the consumption of a wide prey base. Appropriate nest sites (quarries and caves) appeared to increase population numbers and, therefore, should be protected Further studies should determine whether increasing artificial nest sites and reclaiming abandoned quarries could increase eagle owl numbers in a sustainable manner.
Comparison of Four Systems for SARS-CoV-2 Antibody at Three Time Points after SARS-CoV-2 Vaccination
Authors: Seo Jong Do , Nam Minjeong , Lee Tae Hwan , Ahn Yeon-Sun , Shin Seon-Hyeon , Han Hye Young , Moon Hee-Won
Published: May 2022

Background: Immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wanes over time after vaccination. Methods: We compared SARS-CoV-2 antibody levels in serial samples from 350 vaccinated individuals at 3 time points (3 weeks after the first or second dose and before the third dose) with 4 assays: GenScript cPASS SARS-CoV-2 neutralization antibody detection kits (cPASS), Siemens SARS-CoV-2 IgG (sCOVG), Abbott SARS-CoV-2 IgG II Quant (CoV-2 IgG II), and an Immuno-On™ COVID-19 IgG test (Immuno-On IgG). Antibody levels by time, concordance between assays, and values from other tests corresponding to the percent inhibition results in cPASS were assessed. Results: The median values at three time points were 49.31%, 90.87%, and 53.38% inhibition for cPASS, 5.39, 13.65, and 2.24 U/mL for sCOVG, 570.25, 1279.65, and 315.80 AU/mL for CoV-2 IgG II, and 223.22, 362.20, and 62.20 relative units (RU) for Immuno-On IgG. The concordance with cPASS at each time point ranged from 0.735 to 0.984, showing the highest concordance in the second sample and lowest concordance in the third in all comparative tests. The values corresponded to 30% inhibition, and the cutoffs of cPASS, were 2.02 U/mL, 258.6 AU/mL, and 74.2 RU for each test. Those for 50%, 70%, and 90% inhibition were 3.16, 5.66, and 8.26 U/mL for sCOVG, while they were 412.5, 596.9, and 1121.6 AU/mL for CoV-2 IgG II and 141.8, 248.92, and 327.14 RU for Immuno-On IgG. Conclusions: This study demonstrated the dynamic changes in antibody values at different time points using four test systems and is expected to provide useful baseline data for comparative studies and standardization efforts in the future.