bluuebunny/crossref_metadata_2025 huggingface dataset:
Venus’ Cloud-Tracked Winds Using Ground- and Space-Based Observations with TNG/NICS and VEx/VIRTIS
Authors: Machado Pedro , Peralta Javier , Silva José E. , Brasil Francisco , Gonçalves Ruben , Silva Miguel
Published: February 2022

Characterizing the wind speeds of Venus and their variability at multiple vertical levels is essential for a better understanding of the atmospheric superrotation, constraining the role of large-scale planetary waves in the maintenance of this superrotation, and in studying how the wind field affects clouds’ distribution. Here, we present cloud-tracked wind results of the Venus nightside, obtained with unprecedented quality using ground-based observations during July 2012 with the near-infrared camera and spectrograph (NICS) of the Telescopio Nazionale Galileo (TNG) in La Palma. These observations were performed during 3 consecutive days for periods of 2.5 h starting just before dawn, sensing the nightside lower clouds of Venus close to 48 km of altitude with images taken at continuum K filter at 2.28 μm. Our observations cover a period of time when ESA’s Venus Express was not able to observe these deeper clouds of Venus due to a failure in the infrared channel of its imaging spectrometer, VIRTIS-M, and the dates were chosen to coordinate these ground-based observations with Venus Express’ observations of the dayside cloud tops (at about 70 km) with images at 380 nm acquired with the imaging spectrometer VIRTIS-M. Thanks to the quality and spatial resolution of TNG/NICS images and the use of an accurate technique of template matching to perform cloud tracking, we present the most detailed and complete profile of wind speeds ever performed using ground-based observations of Venus. The vertical shear of the wind was also obtained for the first time, obtained by the combination of ground-based and space-based observations, during the Venus Express mission since the year 2008, when the infrared channel of VIRTIS-M stopped working. Our observations exhibit day-to-day changes in the nightside lower clouds, the probable manifestation of the cloud discontinuity, no relevant variations in the zonal winds, and an accurate characterization of their decay towards the poles, along with the meridional circulation. Finally, we also present the latitudinal profiles of zonal winds, meridional winds, and vertical shear of the zonal wind between the upper clouds’ top and lower clouds, confirming previous findings by Venus Express.
USP15 in Cancer and Other Diseases: From Diverse Functionsto Therapeutic Targets
Authors: Li Yan-Chi , Cai Song-Wang , Shu Yu-Bin , Chen Mei-Wan , Shi Zhi
Published: February 2022

The process of protein ubiquitination and deubiquitination plays an important role in maintaining protein stability and regulating signal pathways, and protein homeostasis perturbations may induce a variety of diseases. The deubiquitination process removes ubiquitin molecules from the protein, which requires the participation of deubiquitinating enzymes (DUBs). Ubiquitin-specific protease 15 (USP15) is a DUB that participates in many biological cell processes and regulates tumorigenesis. A dislocation catalytic triplet was observed in the USP15 structure, a conformation not observed in other USPs, except USP7, which makes USP15 appear to be unique. USP15 has been reported to be involved in the regulation of various cancers and diseases, and the reported substrate functions of USP15 are conflicting, suggesting that USP15 may act as both an oncogene and a tumor suppressor in different contexts. The importance and complexity of USP15 in the pathological processes remains unclear. Therefore, we reviewed the diverse biological functions of USP15 in cancers and other diseases, suggesting the potential of USP15 as an attractive therapeutic target.
Association between Endometriosis and Delivery Outcomes: A Systematic Review and Meta-Analysis
Authors: Nagase Yoshikazu , Matsuzaki Shinya , Ueda Yutaka , Kakuda Mamoru , Kakuda Sahori , Sakaguchi Hitomi , Maeda Michihide , Hisa Tsuyoshi , Kamiura Shoji
Published: February 2022

Endometriosis is a common benign gynecological disorder; however, delivery outcomes concerning pregnancies with endometriosis remain understudied. This study aimed to assess the effect of endometriosis on delivery outcomes, including the rate of instrumental delivery, cesarean delivery (CD), postpartum hemorrhage (PPH), and perioperative complications during CD. A systematic literature review was conducted using multiple computerized databases, and 28 studies met the inclusion criteria. Pooled analysis showed that histologically diagnosed endometriosis was associated with an increased rate of instrumental delivery (odds ratio [OR] 1.26, 95% confidence interval [CI] 1.02–1.56) and an increased risk of CD (adjusted OR 2.59, 95%CI 1.32–5.07). In our analysis, histologically diagnosed endometriosis was not associated with an increased rate of PPH; however, one retrospective study reported that endometriosis increased the rate of PPH during CD (adjusted OR 1.7, 95%CI 1.5–2.0). Two studies examined perioperative complications during CD, and women with deep endometriosis had a higher rate of bowel resection or bladder injury than those without endometriosis. Our findings suggest that endometriosis is a significant risk factor for instrumental delivery and CD and may be associated with a higher rate of PPH and intraoperative complications during CD.
FDTD Analysis of Hotspot-Enabling Hybrid Nanohole-Nanoparticle Structures for SERS Detection
Authors: Gomez-Cruz Juan , Bdour Yazan , Stamplecoskie Kevin , Escobedo Carlos
Published: February 2022

Metallic nanoparticles (MNPs) and metallic nanostructures are both commonly used, independently, as SERS substrates due to their enhanced plasmonic activity. In this work, we introduce and investigate a hybrid nanostructure with strong SERS activity that benefits from the collective plasmonic response of the combination of MNPs and flow-through nanohole arrays (NHAs). The electric field distribution and electromagnetic enhancement factor of hybrid structures composed of silver NPs on both silver and gold NHAs are investigated via finite-difference time-domain (FDTD) analyses. This computational approach is used to find optimal spatial configurations of the nanoparticle positions relative to the nanoapertures and investigate the difference between Ag-NP-on-Ag-NHAs and Ag-NP-on-Au-NHAs hybrid structures. A maximum GSERS value of 6.8 × 109 is achieved with the all-silver structure when the NP is located 0.5 nm away from the rim of the NHA, while the maximum of 4.7 × 1010 is obtained when the nanoparticle is in full contact with the NHA for the gold-silver hybrid structure. These results demonstrate that the hybrid nanostructures enable hotspot formation with strong SERS activity and plasmonic enhancement compatible with SERS-based sensing applications.
The Role of Body in Brain Plasticity
Authors: Pazzaglia Mariella
Published: February 2022

Our bodily experience arises primarily from the integration of sensory, interoceptive, and motor signals and is mapped directly into the sensorimotor cortices [...]
Mindfulness-Based Interventions for the Treatment of Aberrant Interoceptive Processing in Substance Use Disorders
Authors: May April C. , Davis Chrysantha , Kirlic Namik , Stewart Jennifer L.
Published: February 2022

Altered interoception, or the processing of bodily signals, has been argued to play a role in the development and maintenance of substance use disorders (SUD). Therefore, interoceptive interventions focusing on bodily awareness, such as mindfulness meditation, may improve treatment outcomes for individuals with SUD. Here we review: (1) subjective, behavioral and brain evidence for altered interoceptive processing in SUD, focusing on insular and anterior cingulate cortices (INS, ACC), key regions for interoceptive processing; (2) research highlighting links between mindfulness and brain function; and (3) extant brain research investigating mindfulness-based interventions in SUD. SUD tend to be characterized by heightened INS and ACC responses to drug cues but blunted interoceptive awareness and attenuated INS and ACC responses during tasks involving bodily attention and/or perturbations. In contrast, mindfulness interventions in healthy individuals are linked to enhanced INS and ACC responses and heightened interoceptive awareness. It is crucial for future research to identify: (1) whether mindfulness-based treatments are efficacious across substance classes; (2) what particular approaches and dosages show the largest effect sizes in enhancing INS and ACC function to non-drug stimuli and reducing responsivity to substance cues, thereby improving SUD treatment outcomes (reducing drug craving and relapse).
A Hebbian Approach to Non-Spatial Prelinguistic Reasoning
Authors: Aguilar-Canto Fernando , Calvo Hiram
Published: February 2022

This research integrates key concepts of Computational Neuroscience, including the Bienestock-CooperMunro (BCM) rule, Spike Timing-Dependent Plasticity Rules (STDP), and the Temporal Difference Learning algorithm, with an important structure of Deep Learning (Convolutional Networks) to create an architecture with the potential of replicating observations of some cognitive experiments (particularly, those that provided some basis for sequential reasoning) while sharing the advantages already achieved by the previous proposals. In particular, we present Ring Model B, which is capable of associating visual with auditory stimulus, performing sequential predictions, and predicting reward from experience. Despite its simplicity, we considered such abilities to be a first step towards the formulation of more general models of prelinguistic reasoning.
Characterization of the pVHL Interactome in Human Testis Using High-Throughput Library Screening
Authors: Falconieri Antonella , Minervini Giovanni , Quaglia Federica , Sartori Geppo , Tosatto Silvio C. E.
Published: February 2022

Functional impairment of the von Hippel–Lindau tumor suppressor (pVHL) is causative of a familiar increased risk of developing cancer. As an E3 substrate recognition particle, pVHL marks the hypoxia inducible factor 1α (HIF-1α) for degradation in normoxic conditions, thus acting as a key regulator of both acute and chronic cell adaptation to hypoxia. The male mice model carrying VHL gene conditional knockout presents significant abnormalities in testis development paired with defects in spermatogenesis and infertility, indicating that pVHL exerts testis-specific roles. Here we aimed to explore whether pVHL could have a similar role in humans by performing a testis-tissue library screening complemented with in-depth bioinformatics analysis. We identified 55 novel pVHL binding proteins directly involved in spermatogenesis, cell differentiation and reproductive metabolism. In addition, computational investigation of these new interactors identified multiple pVHL-specific binding motifs and demonstrated that somatic mutations described in human cancers reside in these binding regions. Collectively, these findings suggest that, in addition to its role in cancer formation, pVHL may also be pivotal in normal gonadal development in humans.
Repair-Assisted Damage Detection Reveals Biological Disparities in Prostate Cancer between African Americans and European Americans
Authors: Krieger Kimiko L. , Gohlke Jie H. , Lee Kevin J. , Piyarathna Danthasinghe Waduge Badrajee , Castro Patricia D. , Jones Jeffrey A. , Ittmann Michael M. , Gassman Natalie R. , Sreekumar Arun
Published: February 2022

African Americans (AA) are two times more likely to be diagnosed with and succumb to prostate cancer (PCa) compared to European Americans (EA). There is mounting evidence that biological differences in these tumors contribute to disparities in patient outcomes. Our goal was to examine the differences in DNA damage in AA and EA prostate tissues. Tissue microarrays with matched tumor-benign adjacent pairs from 77 AA and EA PCa patients were analyzed for abasic sites, oxidative lesions, crosslinks, and uracil content using the Repair Assisted Damage Detection (RADD) assay. Our analysis revealed that AA PCa, overall, have more DNA damage than EA PCa. Increased uracil and pyrimidine lesions occurred in AA tumors, while EA tumors had more oxidative lesions. AA PCa have higher levels of UMP and folate cycle metabolites than their EA counterparts. AA PCa showed higher levels of UNG, the uracil-specific glycosylase, than EA, despite uracil lesions being retained within the genome. AA patients also had lower levels of the base excision repair protein XRCC1. These results indicate dysfunction in the base excision repair pathway in AA tumors. Further, these findings reveal how metabolic rewiring in AA PCa drives biological disparities and identifies a targetable axis for cancer therapeutics.
Tumor Microenvironment and Hydrogel-Based 3D Cancer Models for In Vitro Testing Immunotherapies
Authors: Vitale Chiara , Marzagalli Monica , Scaglione Silvia , Dondero Alessandra , Bottino Cristina , Castriconi Roberta
Published: February 2022

In recent years, immunotherapy has emerged as a promising novel therapeutic strategy for cancer treatment. In a relevant percentage of patients, however, clinical benefits are lower than expected, pushing researchers to deeply analyze the immune responses against tumors and find more reliable and efficient tools to predict the individual response to therapy. Novel tissue engineering strategies can be adopted to realize in vitro fully humanized matrix-based models, as a compromise between standard two-dimensional (2D) cell cultures and animal tests, which are costly and hardly usable in personalized medicine. In this review, we describe the main mechanisms allowing cancer cells to escape the immune surveillance, which may play a significant role in the failure of immunotherapies. In particular, we discuss the role of the tumor microenvironment (TME) in the establishment of a milieu that greatly favors cancer malignant progression and impact on the interactions with immune cells. Then, we present an overview of the recent in vitro engineered preclinical three-dimensional (3D) models that have been adopted to resemble the interplays between cancer and immune cells and for testing current therapies and immunotherapeutic approaches. Specifically, we focus on 3D hydrogel-based tools based on different types of polymers, discussing the suitability of each of them in reproducing the TME key features based on their intrinsic or tunable characteristics. Finally, we introduce the possibility to combine the 3D models with technological fluid dynamics platforms, reproducing the dynamic complex interactions between tumor cells and immune effectors migrated in situ via the systemic circulation, pointing out the challenges that still have to be overcome for setting more predictive preclinical assays.
Machine Learning-Based Analysis of Glioma Grades Reveals Co-Enrichment
Authors: Garbulowski Mateusz , Smolinska Karolina , Çabuk Uğur , Yones Sara A. , Celli Ludovica , Yaz Esma Nur , Barrenäs Fredrik , Diamanti Klev , Wadelius Claes , Komorowski Jan
Published: February 2022

Gliomas develop and grow in the brain and central nervous system. Examining glioma grading processes is valuable for improving therapeutic challenges. One of the most extensive repositories storing transcriptomics data for gliomas is The Cancer Genome Atlas (TCGA). However, such big cohorts should be processed with caution and evaluated thoroughly as they can contain batch and other effects. Furthermore, biological mechanisms of cancer contain interactions among biomarkers. Thus, we applied an interpretable machine learning approach to discover such relationships. This type of transparent learning provides not only good predictability, but also reveals co-predictive mechanisms among features. In this study, we corrected the strong and confounded batch effect in the TCGA glioma data. We further used the corrected datasets to perform comprehensive machine learning analysis applied on single-sample gene set enrichment scores using collections from the Molecular Signature Database. Furthermore, using rule-based classifiers, we displayed networks of co-enrichment related to glioma grades. Moreover, we validated our results using the external glioma cohorts. We believe that utilizing corrected glioma cohorts from TCGA may improve the application and validation of any future studies. Finally, the co-enrichment and survival analysis provided detailed explanations for glioma progression and consequently, it should support the targeted treatment.
Role of Radiology in the Preoperative Detection of Arterial Calcification and Celiac Trunk Stenosis and Its Association with Anastomotic Leakage Post Esophagectomy, an Up-to-Date Review of the Literature
Authors: Tzortzakakis Antonios , Kalarakis Georgios , Huang Biying , Terezaki Eleni , Koltsakis Emmanouil , Kechagias Aristotelis , Tsekrekos Andrianos , Rouvelas Ioannis
Published: February 2022

Surgical resection of the esophagus remains a critical component of the multimodal treatment of esophageal cancer. Anastomotic leakage (AL) is the most significant complication following esophagectomy, in terms of clinical implications. Identifying risk factors for AL is important for modifying patient management and improving surgical outcomes. This review aims to examine the role of radiological risk factors for AL after esophagectomy, and in particular, arterial calcification and celiac trunk stenosis. Eligible publications prior to 25 August 2021 were retrieved from Medline and Google Scholar using a predefined search algorithm. A total of 68 publications were identified, of which 9 original studies remained for in-depth analysis. The majority of these studies found correlations between calcifications in the aorta, celiac trunk, and right post-celiac arteries and AL following esophagectomy. Some studies suggest celiac trunk stenosis as a more appropriate surrogate. Our up-to-date review highlights the need for automated quantification of aortic calcifications, as well as the degree of celiac trunk stenosis in preoperative computed tomography in patients undergoing esophagectomy, to obtain robust and reproducible measurements that can be used for a definite correlation.
Molecular Profiling of Well-Differentiated Neuroendocrine Tumours: The Role of ctDNA in Real-World Practice
Authors: Lamarca Angela , Frizziero Melissa , Barriuso Jorge , Kapacee Zainul , Mansoor Wasat , McNamara Mairéad G. , Hubner Richard A. , Valle Juan W.
Published: February 2022

Background: The role of tumour genomic profiling in the clinical management of well-differentiated neuroendocrine tumours (WdNETs) is unclear. Circulating tumour DNA (ctDNA) may be a useful surrogate for tumour tissue when the latter is insufficient for analysis. Methods: Patients diagnosed with WdNETs underwent ctDNA genomic profiling (FoundationLiquid®); non-WdNETs (paraganglioma, goblet cell or poorly-differentiated neuroendocrine carcinoma) were used for comparison. The aim was to determine the rate of: test failure (primary end-point), “pathological alterations” (PAs) (secondary end-point) and patients for whom ctDNA analysis impacted management (secondary end-point). Results: Forty-five patients were included. A total of 15 patients with WdNETs (18 ctDNA samples) were eligible: 8 females (53.3%), median age 63.2 years (range 23.5–86.8). Primary: small bowel (8; 53.3%), pancreas (5; 33.3%), gastric (1; 6.7%) and unknown primary (1; 6.7%); grade (G)1 (n = 5; 33.3%), G2 (9; 60.0%) and G3 (1; 6.7%); median Ki-67: 5% (range 1–30). A total of 30 patients with non-WdNETs (34 ctDNA samples) were included. Five WdNETs samples (27.78%) failed analysis (vs. 17.65% in non-WdNETs; p-value 0.395). Of the 13 WdNET samples with successful ctDNA analyses, PAs were detected in 6 (46.15%) (vs. 82.14% in non-WdNETs; p-value 0.018). In WdNETs, the PA rate was independent of concomitant administration anti-cancer systemic therapies (2/7; 28.57% vs. 4/6; 66.67%; p-value 0.286) at the time of the ctDNA analysis: four, one and one samples had one, two and three PAs, respectively. These were: CDKN2A mutation (mut) (one sample), CHEK2mut (one), TP53mut (one), FGFR2 amplification (one), IDH2mut (one), CTNNB1mut (one), NF1mut (one) and PALB2mut (one). None were targetable (0%) or impacted clinical management (0%). There was a lower maximum mutant allele frequency (mMAF) in WdNETs (mean 0.33) vs. non-WdNETs (mean 26.99), even though differences did not reach statistical significance (p-value 0.0584). Conclusions: Although feasible, mutation-based ctDNA analysis was of limited clinical utility for patients with advanced WdNETs. The rates of PAs and mMAFs were higher in non-WdNETs. While patients with WdNETs could still be offered genomic profiling (if available and reimbursed), it is important to manage patients’ expectations regarding the likelihood of the results impacting their treatment.
A Comprehensive Review of the Current and Future Role of the Microbiome in Pancreatic Ductal Adenocarcinoma
Authors: Merali Nabeel , Chouari Tarak , Kayani Kayani , Rayner Charles J. , Jiménez José I. , Krell Jonathan , Giovannetti Elisa , Bagwan Izhar , Relph Kate , Rockall Timothy A. , Dhillon Tony , Pandha Hardev , Annels Nicola E. , Frampton Adam E.
Published: February 2022

Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second most common cause of cancer death in the USA by 2030, yet progress continues to lag behind that of other cancers, with only 9% of patients surviving beyond 5 years. Long-term survivorship of PDAC and improving survival has, until recently, escaped our understanding. One recent frontier in the cancer field is the microbiome. The microbiome collectively refers to the extensive community of bacteria and fungi that colonise us. It is estimated that there is one to ten prokaryotic cells for each human somatic cell, yet, the significance of this community in health and disease has, until recently, been overlooked. This review examines the role of the microbiome in PDAC and how it may alter survival outcomes. We evaluate the possibility of employing microbiomic signatures as biomarkers of PDAC. Ultimately this review analyses whether the microbiome may be amenable to targeting and consequently altering the natural history of PDAC.
In Situ N-Glycosylation Signatures of Epithelial Ovarian Cancer Tissue as Defined by MALDI Mass Spectrometry Imaging
Authors: Grzeski Marta , Taube Eliane T. , Braicu Elena I. , Sehouli Jalid , Blanchard Véronique , Klein Oliver
Published: February 2022

The particularly high mortality of epithelial ovarian cancer (EOC) is in part linked to limited understanding of its molecular signatures. Although there are data available on in situ N-glycosylation in EOC tissue, previous studies focused primarily on neutral N-glycan species and, hence, still little is known regarding EOC tissue-specific sialylation. In this proof-of-concept study, we implemented MALDI mass spectrometry imaging (MALDI-MSI) in combination with sialic acid derivatization to simultaneously investigate neutral and sialylated N-glycans in formalin-fixed paraffin-embedded tissue microarray specimens of less common EOC histotypes and non-malignant borderline ovarian tumor (BOT). The applied protocol allowed detecting over 50 m/z species, many of which showed differential tissue distribution. Most importantly, it could be demonstrated that α2,6- and α2,3-sialylated N-glycans are enriched in tissue regions corresponding to tumor and adjacent tumor-stroma, respectively. Interestingly, analogous N-glycosylation patterns were observed in tissue cores of BOT, suggesting that regio-specific N-glycan distribution might occur already in non-malignant ovarian pathologies. All in all, our data provide proof that the combination of MALDI-MSI and sialic acid derivatization is suitable for delineating regio-specific N-glycan distribution in EOC and BOT tissues and might serve as a promising strategy for future glycosylation-based biomarker discovery studies.
Transcriptional Factor Repertoire of Breast Cancer in 3D Cell Culture Models
Authors: Özkan Hande , Öztürk Deniz Gülfem , Korkmaz Gozde
Published: February 2022

Intratumor heterogeneity of breast cancer is driven by extrinsic factors from the tumor microenvironment (TME) as well as tumor cell–intrinsic parameters including genetic, epigenetic, and transcriptomic traits. The extracellular matrix (ECM), a major structural component of the TME, impacts every stage of tumorigenesis by providing necessary biochemical and biomechanical cues that are major regulators of cell shape/architecture, stiffness, cell proliferation, survival, invasion, and migration. Moreover, ECM and tissue architecture have a profound impact on chromatin structure, thereby altering gene expression. Considering the significant contribution of ECM to cellular behavior, a large body of work underlined that traditional two-dimensional (2D) cultures depriving cell–cell and cell–ECM interactions as well as spatial cellular distribution and organization of solid tumors fail to recapitulate in vivo properties of tumor cells residing in the complex TME. Thus, three-dimensional (3D) culture models are increasingly employed in cancer research, as these culture systems better mimic the physiological microenvironment and shape the cellular responses according to the microenvironmental cues that will regulate critical cell functions such as cell shape/architecture, survival, proliferation, differentiation, and drug response as well as gene expression. Therefore, 3D cell culture models that better resemble the patient transcriptome are critical in defining physiologically relevant transcriptional changes. This review will present the transcriptional factor (TF) repertoire of breast cancer in 3D culture models in the context of mammary tissue architecture, epithelial-to-mesenchymal transition and metastasis, cell death mechanisms, cancer therapy resistance and differential drug response, and stemness and will discuss the impact of culture dimensionality on breast cancer research.
Quantitative Analysis of Plasma Cell-Free DNA and Its DNA Integrity and Hypomethylation Status as Biomarkers for Tumor Burden and Disease Progression in Patients with Metastatic Neuroendocrine Neoplasias
Authors: Mettler Esther , Fottner Christian , Bakhshandeh Neda , Trenkler Anja , Kuchen Robert , Weber Matthias M.
Published: February 2022

Background: Neuroendocrine neoplasia (NEN) encompasses a diverse group of malignancies marked by histological heterogeneity and highly variable clinical outcomes. Apart from Chromogranin A, specific biomarkers predicting residual tumor disease, tumor burden, and disease progression in NEN are scant. Thus, there is a strong clinical need for new and minimally invasive biomarkers that allow for an evaluation of the prognosis, clinical course, and response to treatment of NEN patients, thereby helping implement individualized treatment decisions in this heterogeneous group of patients. In the current prospective study, we evaluated the role of plasma cell-free DNA concentration and its global hypomethylation and fragmentation as possible diagnostic and prognostic biomarkers in patients with neuroendocrine neoplasias. Methods: The plasma cfDNA concentration, cfDNA Alu hypomethylation, and LINE-1 cfDNA integrity were evaluated prospectively in 63 NEN patients with presumably cured or advanced metastatic disease. The cfDNA characteristics in NEN patients were compared to the results of a group of 29 healthy controls and correlated with clinical and histopathological data of the patients. Results: Patients with advanced NEN showed a significantly higher cfDNA concentration and percentage of Alu hypomethylation and a reduced LINE-1 cfDNA integrity as compared to the surgically cured NET patients and the healthy control group. The increased hypomethylation and concentration of cfDNA and the reduced cfDNA integrity in NEN patients were strongly associated with tumor burden and poor prognosis, while no correlation with tumor grading, differentiation, localization, or hormonal activity could be found. Multiparametric ROC analysis of plasma cfDNA characteristics was able to distinguish NEN patients with metastatic disease from the control group and the cured NEN patients with AUC values of 0.694 and 0.908, respectively. This was significant even for the group with only a low tumor burden. Conclusions: The present study, for the first time, demonstrates that the combination of plasma cfDNA concentration, global hypomethylation, and fragment length pattern has the potential to serve as a potent and sensitive prognostic and therapeutic “liquid biopsy” biomarker for tumor burden and disease progression in patients with neuroendocrine neoplasias.
Prognostic and Predictive Molecular Markers in Cholangiocarcinoma
Authors: Pavicevic Sandra , Reichelt Sophie , Uluk Deniz , Lurje Isabella , Engelmann Cornelius , Modest Dominik P. , Pelzer Uwe , Krenzien Felix , Raschzok Nathanael , Benzing Christian , Sauer Igor M. , Stintzing Sebastian , Tacke Frank , Schöning Wenzel , Schmelzle Moritz , Pratschke Johann , Lurje Georg
Published: February 2022

Cholangiocarcinoma (CCA) is the second most common primary liver cancer and subsumes a heterogeneous group of malignant tumors arising from the intra- or extrahepatic biliary tract epithelium. A rising mortality from CCA has been reported worldwide during the last decade, despite significant improvement of surgical and palliative treatment. Over 50% of CCAs originate from proximal extrahepatic bile ducts and constitute the most common CCA entity in the Western world. Clinicopathological characteristics such as lymph node status and poor differentiation remain the best-studied, but imperfect prognostic factors. The identification of prognostic molecular markers as an adjunct to traditional staging systems may not only facilitate the selection of patients who would benefit the most from surgical, adjuvant or palliative treatment strategies, but may also be helpful in defining the aggressiveness of the disease and identifying patients at high-risk for tumor recurrence. The purpose of this review is to provide an overview of currently known molecular prognostic and predictive markers and their role in CCA.
Immunotherapy for Colorectal Cancer: Mechanisms and Predictive Biomarkers
Authors: Carlsen Lindsey , Huntington Kelsey E. , El-Deiry Wafik S.
Published: February 2022

Though early-stage colorectal cancer has a high 5 year survival rate of 65–92% depending on the specific stage, this probability drops to 13% after the cancer metastasizes. Frontline treatments for colorectal cancer such as chemotherapy and radiation often produce dose-limiting toxicities in patients and acquired resistance in cancer cells. Additional targeted treatments are needed to improve patient outcomes and quality of life. Immunotherapy involves treatment with peptides, cells, antibodies, viruses, or small molecules to engage or train the immune system to kill cancer cells. Preclinical and clinical investigations of immunotherapy for treatment of colorectal cancer including immune checkpoint blockade, adoptive cell therapy, monoclonal antibodies, oncolytic viruses, anti-cancer vaccines, and immune system modulators have been promising, but demonstrate limitations for patients with proficient mismatch repair enzymes. In this review, we discuss preclinical and clinical studies investigating immunotherapy for treatment of colorectal cancer and predictive biomarkers for response to these treatments. We also consider open questions including optimal combination treatments to maximize efficacy, minimize toxicity, and prevent acquired resistance and approaches to sensitize mismatch repair-proficient patients to immunotherapy.
Working Space Creation in Transoral Thyroidectomy: Pearls and Pitfalls
Authors: Liang Tsung-Jung , Chen I-Shu , Liu Shiuh-Inn
Published: February 2022

Transoral thyroidectomy is a novel technique that uses three small incisions hidden in the oral vestibule to remove the thyroid gland. It provides excellent cosmetic results and outcomes comparable to the open approach. One of the main obstacles for this technique is the creation of a working space from the lip and chin to the neck. The anatomy of the perioral region and the top-down surgical view are both unfamiliar to general surgeons. As a result, inadequate manipulation might easily occur and would lead to several unconventional complications, such as mental nerve injury, carbon dioxide embolism, and skin perforation, which are rarely observed in open surgery. Herein, we summarize the basic concepts, techniques, and rationales behind working space creation in transoral thyroidectomy to assist surgeons in obtaining an adequate surgical field while eliminating preventable complications.
Microsatellite Status and IκBα Expression Levels Predict Sensitivity to Pharmaceutical Curcumin in Colorectal Cancer Cells
Authors: Lu Lili , Przybylla Randy , Shang Yuru , Dai Meng , Krohn Mathias , Krämer Oliver Holger , Mullins Christina Susanne , Linnebacher Michael
Published: February 2022

Clinical utilization of curcumin in colorectal cancer (CRC) was revived as a result of the development of novel curcumin formulations with improved bioavailability. Additionally, identification of biomarkers for curcumin sensitivity would also promote successful clinical applications. Here, we wanted to identify such biomarkers in order to establish a predictive model for curcumin sensitivity. Thirty-two low-passage CRC cell lines with specified tumor characteristics were included. Curcumin suppressed cell proliferation, yet sensitivity levels were distinct. Most curcumin-sensitive CRC cell lines were microsatellite stable and expressed high levels of IκBα. The predictive capacity of this biomarker combination possessed a statistical significance of 72% probability to distinguish correctly between curcumin-sensitive and -resistant CRC cell lines. Detailed functional analyses were performed with three sensitive and three resistant CRC cell lines. As curcumin’s mode of action, inhibition of NF-κB p65 activation via IκBα was identified. In consequence, we hypothesize that novel curcumin formulations—either alone or, more likely, in combination with standard therapeutics—can be expected to prove clinically beneficial for CRC patients with high IκBα expression levels.
Acknowledgment to Reviewers of Cardiogenetics in 2021
Authors:   Cardiogenetics Editorial Office
Published: February 2022

Rigorous peer-reviews are the basis of high-quality academic publishing [...]
Targeting Protein O-GlcNAcylation, a Link between Type 2 Diabetes Mellitus and Inflammatory Disease
Authors: Bolanle Israel , Palmer Timothy
Published: February 2022

Unresolved hyperglycaemia, a hallmark of type 2 diabetes mellitus (T2DM), is a well characterised manifestation of altered fuel homeostasis and our understanding of its role in the pathologic activation of the inflammatory system continues to grow. Metabolic disorders like T2DM trigger changes in the regulation of key cellular processes such as cell trafficking and proliferation, and manifest as chronic inflammatory disorders with severe long-term consequences. Activation of inflammatory pathways has recently emerged as a critical link between T2DM and inflammation. A substantial body of evidence has suggested that this is due in part to increased flux through the hexosamine biosynthetic pathway (HBP). The HBP, a unique nutrient-sensing metabolic pathway, produces the activated amino sugar UDP-GlcNAc which is a critical substrate for protein O-GlcNAcylation, a dynamic, reversible post-translational glycosylation of serine and threonine residues in target proteins. Protein O-GlcNAcylation impacts a range of cellular processes, including inflammation, metabolism, trafficking, and cytoskeletal organisation. As increased HBP flux culminates in increased protein O-GlcNAcylation, we propose that targeting O-GlcNAcylation may be a viable therapeutic strategy for the prevention and management of glucose-dependent pathologies with inflammatory components.
The Role of Mitophagy in Viral Infection
Authors: Li Yuwan , Wu Keke , Zeng Sen , Zou Linke , Li Xiaowen , Xu Chen , Li Bingke , Liu Xiaodi , Li Zhaoyao , Zhu Wenhui , Fan Shuangqi , Chen Jinding
Published: February 2022

Mitophagy, which is able to selectively clear excess or damaged mitochondria, plays a vital role in the quality control of mitochondria and the maintenance of normal mitochondrial functions in eukaryotic cells. Mitophagy is involved in many physiological and pathological processes, including apoptosis, innate immunity, inflammation, cell differentiation, signal transduction, and metabolism. Viral infections cause physical dysfunction and thus pose a significant threat to public health. An accumulating body of evidence reveals that some viruses hijack mitophagy to enable immune escape and self-replication. In this review, we systematically summarize the pathway of mitophagy initiation and discuss the functions and mechanisms of mitophagy in infection with classical swine fever virus and other specific viruses, with the aim of providing a theoretical basis for the prevention and control of related diseases.
miR172 Regulates WUS during Somatic Embryogenesis in Arabidopsis via AP2
Authors: Nowak Katarzyna , Morończyk Joanna , Grzyb Małgorzata , Szczygieł-Sommer Aleksandra , Gaj Małgorzata D.
Published: February 2022

In plants, the embryogenic transition of somatic cells requires the reprogramming of the cell transcriptome, which is under the control of genetic and epigenetic factors. Correspondingly, the extensive modulation of genes encoding transcription factors and miRNAs has been indicated as controlling the induction of somatic embryogenesis in Arabidopsis and other plants. Among the MIRNAs that have a differential expression during somatic embryogenesis, members of the MIRNA172 gene family have been identified, which implies a role of miR172 in controlling the embryogenic transition in Arabidopsis. In the present study, we found a disturbed expression of both MIRNA172 and candidate miR172-target genes, including AP2, TOE1, TOE2, TOE3, SMZ and SNZ, that negatively affected the embryogenic response of transgenic explants. Next, we examined the role of AP2 in the miR172-mediated mechanism that controls the embryogenic response. We found some evidence that by controlling AP2, miR172 might repress the WUS that has an important function in embryogenic induction. We showed that the mechanism of the miR172-AP2-controlled repression of WUS involves histone acetylation. We observed the upregulation of the WUS transcripts in an embryogenic culture that was overexpressing AP2 and treated with trichostatin A (TSA), which is an inhibitor of HDAC histone deacetylases. The increased expression of the WUS gene in the embryogenic culture of the hdac mutants further confirmed the role of histone acetylation in WUS control during somatic embryogenesis. A chromatin-immunoprecipitation analysis provided evidence about the contribution of HDA6/19-mediated histone deacetylation to AP2-controlled WUS repression during embryogenic induction. The upstream regulatory elements of the miR172-AP2-WUS pathway might involve the miR156-controlled SPL9/SPL10, which control the level of mature miR172 in an embryogenic culture.
Professionals’ Views on Challenges in Inpatient Substance Abuse Treatment during COVID-19 Pandemic in Finland
Authors: Ekqvist Eeva , Karsimus Tuija , Ruisniemi Arja , Kuusisto Katja
Published: February 2022

The pandemic caused by COVID-19 (an acute respiratory illness caused by a coronavirus) has had harmful effects on people in need of special support. People with problematic substance use are recognized as such a group. The pandemic has raised the need for sufficient treatment and services during these unpredictable conditions. At the same time, it poses severe challenges to their production and provision. The purpose of the study was to use content analysis to qualitatively examine Finnish professionals’ (N = 22) views on (1) the challenges posed by COVID-19 in working in inpatient substance abuse treatment, (2) how these challenges have been addressed, and (3) what the consequences of the challenges and the solutions to them are. The findings confirmed that COVID-19 has caused drastic changes in the organization of treatment and daily practices. Professionals experience challenges in preventing infection from spreading into and within treatment units. They also describe difficulties in applying social distancing in treatment that is based on therapeutic communities. The pandemic has also challenged communication and co-worker support among professionals. These challenges have led to practical solutions that, in turn, have their own consequences for treatment practices. We conclude that the quality of treatment has to some extent been impaired because of the pandemic.
Finding the True Number of Females with Autistic Spectrum Disorder by Estimating the Biases in Initial Recognition and Clinical Diagnosis
Authors: McCrossin Robert
Published: February 2022

The proportion of females whose ASD diagnosis is missed is unknown. The ratio of males to females with ASD is generally quoted as 4:1, though it is believed that there are biases preventing females from being diagnosed and that the true ratio is lower. These biases have not been clearly identified or quantified. Starting with a clinical dataset of 1711 children <18 years old, four different methods were employed in an inductive study to identify and quantify the biases and calculate the proportion of females missed. A mathematical model was constructed to compare the findings with current published data. The true male-to-female ratio appears to be 3:4. Eighty percent of females remain undiagnosed at age 18, which has serious consequences for the mental health of young women.
Bereaved Parent Perspectives on End-of-Life Conversations in Pediatric Oncology
Authors: Robert Rhonda , Razvi Shehla , Triche Lisa L. , Bruera Eduardo , Moody Karen M.
Published: February 2022

Background: Professional education pertaining to end-of-life care with pediatric oncology patients is limited. Pediatric trainees learn about end-of-life conversations largely from the provider’s perspective. Bereaved parents can inform the education of oncologists and the interdisciplinary team by sharing their perceptions and preferences through personal narratives. Methods: The aim of this project was to enhance the healthcare teams’ understanding of bereaved parents’ end-of-life care preferences through narratives. Bereaved parents were recruited from our institution’s Pediatric Supportive Care Committee membership. Parents were tasked with identifying elements of care that were of the greatest importance to them, based upon their personal experiences during their child’s end-of-life care. Narratives were analyzed using standard qualitative methods. Results: Parents of five patients participated, including four mothers and three fathers. Ten themes summarizing essential elements of end-of-life care were identified, including early ongoing and stepwise prognostic disclosure, honoring the child’s voice, support of hope and realism, anticipatory guidance on dying, and continued contact with the bereaved. Conclusion: Bereaved parents emphasize the need for providers to have ongoing honest conversations that support realism and hope that can help them to best prepare for their child’s end of life and to remain in contact with them after death.
Association of Weight Changes by Three Days after Birth and Mortality and/or Severe Neurological Injury in Preterm Infants < 29 Weeks Gestational Age: A Multicenter Cohort Study
Authors: Zozaya Carlos , Aziz Khalid , Singhal Nalini , Ye Xiang Y. , Drolet Christine , Emberley Julie , Lee Kyong-Soon , Shah Vibhuti S. ,   on behalf of the Canadian Neonatal Network (CNN) Investigators
Published: February 2022

Objective: This study aimed to determine the range of weight loss, at 3 days postnatal age, associated with the lowest risk of mortality/short-term morbidity in preterm infants <29 weeks gestational age (GA). Study design: This multicenter retrospective cohort study employed data from the Canadian Neonatal Network database. The primary outcome was a composite of mortality and/or severe neurological injury. Multivariable quadratic and linear regression models which adjusted for potential confounders were built. Results: A total of 9275 preterm infants (median GA 26, IQR 25, 28 weeks) were included. The optimal weight change range at day three, after adjustment for potential confounders for the primary outcomes, was −15 to −8.9%. Conclusions: There is a ‘U’-shaped relationship between weight change from birth to day three and mortality and/or severe neurological injury. Interventional studies, which target weight loss within the range found in this study and evaluate the impact on neonatal outcomes, are needed to corroborate our findings.
Comparative Study on Road Performance of Low-Grade Hard Asphalt and Mixture in China and France
Authors: Zeng Guodong , Wu Wenjuan , Li Juechi , Xu Qinsheng , Li Xianghang , Yan Xiangpeng , Han Ye , Wei Jincheng
Published: February 2022

The high-modulus asphalt mixture produced by hard asphalt has played a good role in reducing asphalt pavement rutting and improving pavement durability. It was widely used in the construction of various levels of road engineering in Europe. However, low-grade hard asphalt was rarely used in road engineering in China, and the use of hard asphalt for the design and construction of high modulus asphalt mixtures lacks sufficient engineering experience. Considering the above issues, comparative research on the performance of Chinese and French low-grade hard asphalt and mixture was carried out. In this paper, the performance of French 15# hard asphalt commonly used for EME (Enrobés à Module Elevé Class) high modulus asphalt mixture and China 15# hard asphalt was analyzed comparatively, where six typical high modulus asphalt mixtures corresponding to two low-grade hard asphalts were designed referring to the design requirements of French high modulus asphalt mixtures. The road performance of a high-modulus asphalt mixture was evaluated to verify the feasibility of its application in engineering. The research results show that the performance indicators of both Chinese and French asphalts meet the requirements of binder materials used in high modulus asphalt mixtures, and the performance of their corresponding mixtures of the two asphalts also meet the specifications of high modulus asphalt mixtures. However, the two asphalts and the performance of their corresponding mixture are slightly different. The high modulus asphalt mixture of Chinese low-grade hard bitumen can be used well in road engineering applications in China. It can strongly promote the wide application of high modulus asphalt mixture in China.
Optical Behavior of Curcuminoid Hybrid Systems as Coatings Deposited on Polyester Fibers
Authors: Raduly Florentina Monica , Rădiţoiu Valentin , Rădiţoiu Alina , Purcar Violeta , Ispas Georgiana , Frone Adriana Nicoleta , Gabor Raluca Augusta , Nicolae Cristian-Andi
Published: February 2022

The recent development of the “eco-friendly” current has brought to the attention of researchers natural dyes that are biodegradable, do not cause allergies and generally have anti-UV protection, and antioxidant and antibacterial properties. In this study, we aimed to obtain hybrid materials of the dye–host matrix type, by using the sol–gel process. The silica network was generated by tetraethylorthosilicates and modified with organic siloxane derivatives: phenyltriethoxysilane, 3-glycidoxypropyltriethoxysilane, dimethoxydimethylsilane and dimethoxydiphenylsilane. The nanocomposites obtained by embedding curcumin in siloxane matrices were deposited on polyester fabric and evaluated for their properties, relative to the type of organic network modifier used. Fabrics covered with curcuminoid hybrid systems provide a hydrophobic surface, have fluorescent properties and a UPF +50, and, therefore, they can be used in various fields where it is necessary for textiles to provide signaling, self-cleaning or protection properties against ultraviolet radiation. The coated textile materials have very good resistance properties after several repeated washing cycles, and maintain the original UV protection factor at high values even after washing or during rubbing tests.