bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on the Fatigue Life Prediction for a New Modified Asphalt Mixture of a Support Vector Machine Based on Particle Swarm Optimization
Authors: Sun Yu , He Dongpo , Li Jun
Published: December 2021

SMC (Styreneic Methyl Copolymers) is a novel normal temperature asphalt modifier with superior performance. It has the advantages of a low construction temperature, good road performance, good energy savings and an emission reduction effect, and can improve the performance of an asphalt mixture. The fatigue performance of an asphalt mixture is one of the important technical parameters in the structural design of asphalt pavements. The fatigue performance of an asphalt mixture under specific traffic and environmental conditions has an important guiding significance and normative function for the design, construction, and maintenance of asphalt pavement. In this paper, the mixture of an SMC normal-temperature-modified asphalt and styrene–butadiene styrene block copolymer (SBS)-modified asphalt (SMCSBS) compound-modified asphalt was investigated, and an SMCSBS composite modified asphalt mixture with a different SMC content was prepared. A semi-circular bending fatigue test (SCB) was conducted to analyze and compare the fatigue properties of the modified asphalt mixture. On this basis, this paper proposes a fatigue life prediction model of an SMCSBS composite modified asphalt mixture based on a particle swarm optimization support vector machine (PSO-SVM). SMC content (SMC accounts for the mass percentage of SMCSBS composite modified asphalt)/%, asphalt aggregate ratio, stress ratio and loading frequency/Hz were used as training data to establish the prediction model, and RMSE and R2 were used to evaluate the performance of the model. Experimental results show that the prediction results of the PSO-SVM method are more accurate than the experimental observation data and can effectively improve the prediction accuracy of the model. Compared with the M5′ model tree (M5′), artificial neural network (ANN), and support vector machine (SVM) method, the PSO-SVM method can achieve better prediction performance and a better prediction effect.
Slightly Acidic Electrolyzed Water to Remove Methylobacterium mesophilicum, Rhodotorula mucilaginosa and Cladosporium cladosporioides in Households
Authors: Naka Angelica , Nakamura Kenji , Kurahashi Midori
Published: December 2021

(1) Background: Slightly acidic electrolyzed water (SAEW) is an effective and safe sterilizing solution. Its active component is hypochlorous acid (HOCl) which has been proved to exhibit a strong disinfectant activity. In this research we evaluated the effectiveness of SAEW in the removal of Methylobacterium mesophilicum, Rhodotorula mucilaginosa and Cladosporium cladosporioides, responsible for pink-colored biofilm and black mold in households. (2) Methods: Two concentrations of SAEW, 20 mg/L and 40 mg/L, were tested against M. mesophilicum, R. mucilaginosa and C. cladosporioides. In vitro experiments and mesh experiments were conducted to test the effectiveness of SAEW. (3) Results: The test results showed that 40 mg/L SAEW was effective in removing R. mucilaginosa and C. cladosporioides, with the population decreasing by approximately two orders of magnitude. For M. mesophilicum, resistance towards SAEW was observed; to obtain a 1.3 order of magnitude decrease in bacterial population, washing 5 times with 40 mg/L SAEW was necessary. Mesh experiments showed that SAEW can remove black mold; (4) Conclusions: Overall results indicated that SAEW was particularly effective for R. mucilaginosa and C. cladosporioides species commonly found in Japanese households.
Assessing the Impact of Dropsonde Data on Rain Forecasts in Taiwan with Observing System Simulation Experiments
Authors: Chien Fang-Ching , Chiu Yen-Chao
Published: December 2021

This paper presents an observing system simulation experiment (OSSE) study to examine the impact of dropsonde data assimilation (DA) on rainfall forecasts for a heavy rain event in Taiwan. The rain event was associated with strong southwesterly flows over the northern South China Sea (SCS) after a weakening tropical cyclone (TC) made landfall over southeastern China. With DA of synthetic dropsonde data over the northern SCS, the model reproduces more realistic initial fields and a better simulated TC track that can help in producing improved low-level southwesterly flows and rainfall forecasts in Taiwan. Dropsonde DA can also aid the model in reducing the ensemble spread, thereby producing more converged ensemble forecasts. The sensitivity studies suggest that dropsonde DA with a 12-h cycling interval is the best strategy for deriving skillful rainfall forecasts in Taiwan. Increasing the DA interval to 6 h is not beneficial. However, if the flight time is limited, a 24-h interval of DA cycling is acceptable, because rainfall forecasts in Taiwan appear to be satisfactory. It is also suggested that 12 dropsondes with a 225-km separation distance over the northern SCS set a minimum requirement for enhancing the model regarding rainfall forecasts. Although more dropsonde data can help the model to obtain better initial fields over the northern SCS, they do not provide more assistance to the forecasts of the TC track and rainfall in Taiwan. These findings can be applied to the future field campaigns and model simulations in the nearby regions.
Atmospheric Effects on the Isotopic Composition of Ozone
Authors: Liang Mao-Chang , Chen Yi-Chun , Gao Yi-Qin , Zhang Xi , Yung Yuk L.
Published: December 2021

The delta values of the isotope composition of atmospheric ozone is ~100‰ (referenced to atmospheric O2). Previous photochemical models, which considered the isotope fractionation processes from both formation and photolysis of ozone, predicted δ49O3 and δ50O3 values, in δ49O3 versus δ50O3 space, that are >10‰ larger than the measurements. We propose that the difference between the model and observations could be explained either by the temperature variation, Chappuis band photolysis, or a combination of the two and examine them. The isotopic fractionation associated with ozone formation increases with temperature. Our model shows that a hypothetical reduction of ~20 K in the nominal temperature profile could reproduce the observations. However, this hypothesis is not consistent with temperatures obtained by in situ measurements and NCEP Reanalysis. Photolysis of O3 in the Chappuis band causes O3 to be isotopically depleted, which is supported by laboratory measurements for 18O18O18O but not by recent new laboratory data made at several wavelengths for 49O3 and 50O3. Cloud reflection can significantly enhance the photolysis rate and affect the spectral distribution of photons, which could influence the isotopic composition of ozone. Sensitivity studies that modify the isotopic composition of ozone by the above two mechanisms are presented. We conclude isotopic fractionation occurring in photolysis in the Chappuis band remains the most plausible solution to the model-observation discrepancy. Implications of our results for using the oxygen isotopic signature for constraining atmospheric chemical processes related to ozone, such as CO2, nitrate, and the hydroxyl radical, are discussed.
Review on Atmospheric Ozone Pollution in China: Formation, Spatiotemporal Distribution, Precursors and Affecting Factors
Authors: Yu Ruilian , Lin Yiling , Zou Jiahui , Dan Yangbin , Cheng Chen
Published: December 2021

In recent years, atmospheric ozone pollution has become more and more serious in many areas of China due to the rapid development of industrialization and urbanization. The increase in atmospheric ozone concentration will not only cause harm to the human respiratory tract, nervous system and immune system, but also cause obvious harm to crops, which will lead to reductions in crop production. Therefore, the study of atmospheric ozone pollution should not be ignored in research on the atmospheric environment. In this paper, we summarized the formation mechanisms of atmospheric ozone, the spatiotemporal distribution characteristics of atmospheric ozone in some areas of China, the relationship between atmospheric ozone and its precursors, and the main factors affecting the concentration of atmospheric ozone. Then, the control countermeasures against atmospheric ozone pollution were put forward in combination with the actual situation in China.
Size-Segregated Elemental Profile and Associated Heath Risk Assessment of Road Dust along Major Traffic Corridors in Kolkata Mega City
Authors: Majumdar Deepanjan , Biswas Bratisha , Majumdar Dipanjali , Ray Rupam
Published: December 2021

Particle size distribution (PSD) of road dust has significant repercussions on atmospheric pollution by road dust resuspension. The PSD of road dust at a few major commercial, traffic, and residential sites in Kolkata mega city was analyzed in the size range of <28–2000 µm. Predominance of the coarse size range (212–600 µm followed by 106–212 µm) was observed. In size-segregated road dust, Fe (4.02–31.2 g kg−1) dominated other elements and was followed by Mg (2.13–10.9 g kg−1), Mn (79.2–601 mg kg−1), Li (395.8–506.8 mg kg−1), and others. Fine particles (<28 μm) had higher elemental concentrations than coarser ones. Cd and Li showed the highest degree of enrichment compared to the Earth’s crust, but only Cd posed significant ecological risk due to its high ecological toxicity. Individual elements did not post significant non-cancer health risks, except for Li in children. However, the cumulative non-cancer risk from all toxic elements for children was almost four times higher than the acceptable level. Lifetime exposure to carcinogenic elements at the current level may pose 5 to 6 times higher cancer risk in the adult population than the acceptable risk of one in a million.
DASentimental: Detecting Depression, Anxiety, and Stress in Texts via Emotional Recall, Cognitive Networks, and Machine Learning
Authors: Fatima Asra , Li Ying , Hills Thomas Trenholm , Stella Massimo
Published: December 2021

Most current affect scales and sentiment analysis on written text focus on quantifying valence/sentiment, the primary dimension of emotion. Distinguishing broader, more complex negative emotions of similar valence is key to evaluating mental health. We propose a semi-supervised machine learning model, DASentimental, to extract depression, anxiety, and stress from written text. We trained DASentimental to identify how N = 200 sequences of recalled emotional words correlate with recallers’ depression, anxiety, and stress from the Depression Anxiety Stress Scale (DASS-21). Using cognitive network science, we modeled every recall list as a bag-of-words (BOW) vector and as a walk over a network representation of semantic memory—in this case, free associations. This weights BOW entries according to their centrality (degree) in semantic memory and informs recalls using semantic network distances, thus embedding recalls in a cognitive representation. This embedding translated into state-of-the-art, cross-validated predictions for depression (R = 0.7), anxiety (R = 0.44), and stress (R = 0.52), equivalent to previous results employing additional human data. Powered by a multilayer perceptron neural network, DASentimental opens the door to probing the semantic organizations of emotional distress. We found that semantic distances between recalls (i.e., walk coverage), was key for estimating depression levels but redundant for anxiety and stress levels. Semantic distances from “fear” boosted anxiety predictions but were redundant when the “sad–happy” dyad was considered. We applied DASentimental to a clinical dataset of 142 suicide notes and found that the predicted depression and anxiety levels (high/low) corresponded to differences in valence and arousal as expected from a circumplex model of affect. We discuss key directions for future research enabled by artificial intelligence detecting stress, anxiety, and depression in texts.
Antithrombotic Therapy in the Prevention of Stroke
Authors: Bir Shyamal , Kelley Roger E.
Published: December 2021

Overview: Ischemic stroke is a leading cause of death and disability throughout the world. Antithrombotic therapy, which includes both antiplatelet and anticoagulant agents, is a primary medication of choice for the secondary prevention of stroke. However, the choices vary with the need to incorporate evolving, newer information into the clinical scenario. There is also the need to factor in co-morbid medical conditions as well as the cost ramifications for a particular patient as well as compliance with the regimen. Pertinent Updates: In the acute setting, dual antiplatelet therapy from three weeks to up to three months has become recognized as a reasonable approach for patients with either minor stroke or transient ischemic attack or those with symptoms associated with higher-grade intracranial stenosis. This approach is favored for non-cardioembolic stroke as a cardiogenic mechanism tends to be best managed with attention to the cardiac condition as well as anticoagulant therapy. Risk stratification for recurrent stroke is important in weighing potential risk versus benefits. For example, prolonged dual antiplatelet therapy, with a combination such as aspirin and clopidogrel or aspirin and ticagrelor, tends to have negation of the potential clinical benefit of stroke prevention, over time, by the enhanced bleeding risk. Anticoagulant choices are now impacted by newer agents, initially identified as novel oral anticoagulants (NOACs), which also became associated with “non-vitamin K” agents as they are no longer considered novel. Alternatively, they are now often identified as direct oral anticoagulants (DOACs). They tend to be viewed as superior or non-inferior to warfarin with the caveat that warfarin is still viewed as the agent of choice for stroke prevention in patients with mechanical heart valves. Conclusion: Based upon cumulative information from multiple clinical trials of secondary prevention of stroke, there is an increasing array of approaches in an effort to provide optimal management. Antithrombotic therapy, including in combination with anticoagulant therapy, continues to evolve with the general caveat that “one size does not fit all”. In view of this, we desire to provide an evidence-based approach for the prevention of stroke with antithrombotic agents.
Cerebral Vein Thrombosis in the Antiphospholipid Syndrome: Analysis of a Series of 27 Patients and Review of the Literature
Authors: Jerez-Lienas Alba , Mathian Alexis , Aboab Jenifer , Crassard Isabelle , Hie Miguel , Cohen-Aubart Fleur , Haroche Julien , Wahl Denis , Cervera Ricard , Amoura Zahir
Published: December 2021

(1) Background: The Antiphospholipid Syndrome (APS) is a systemic autoimmune disorder characterized by arterial and/or venous thrombosis, pregnancy morbidity and raised titers of antiphospholipid antibodies. Cerebral vein thrombosis (CVT) is a rare form of cerebrovascular accident and an uncommon APS manifestation; the information in the literature about this feature consists of case reports and small case series. Our purpose is to describe the particular characteristics of CVT when occurs as part of the APS and compare our series with the patients published in the literature. (2) Methods: We conducted a retrospective observational study collecting data from medical records in three referral centers for APS and CVT, and a systematic review of the literature for CVT cases in APS patients. (3) Results: Twenty-seven APS patients with CVT were identified in our medical records, the majority of them diagnosed as primary APS and with the CVT being the first manifestation of the disease; additional risk factors for thrombosis were identified. The review of the literature yielded 86 cases, with similar characteristics as those of our retrospective series. (4) Conclusions: To our knowledge, our study is the largest CVT series in APS patients published to date, providing a unique point of view in this rare thrombotic manifestation.
The Active Segmentation Platform for Microscopic Image Classification and Segmentation
Authors: Vohra Sumit K. , Prodanov Dimiter
Published: December 2021

Image segmentation still represents an active area of research since no universal solution can be identified. Traditional image segmentation algorithms are problem-specific and limited in scope. On the other hand, machine learning offers an alternative paradigm where predefined features are combined into different classifiers, providing pixel-level classification and segmentation. However, machine learning only can not address the question as to which features are appropriate for a certain classification problem. The article presents an automated image segmentation and classification platform, called Active Segmentation, which is based on ImageJ. The platform integrates expert domain knowledge, providing partial ground truth, with geometrical feature extraction based on multi-scale signal processing combined with machine learning. The approach in image segmentation is exemplified on the ISBI 2012 image segmentation challenge data set. As a second application we demonstrate whole image classification functionality based on the same principles. The approach is exemplified using the HeLa and HEp-2 data sets. Obtained results indicate that feature space enrichment properly balanced with feature selection functionality can achieve performance comparable to deep learning approaches. In summary, differential geometry can substantially improve the outcome of machine learning since it can enrich the underlying feature space with new geometrical invariant objects.
Hearing Rehabilitation with Cochlear Implants after CyberKnife Radiosurgery of Vestibular Schwannoma: A Report Based on Four Clinical Cases
Authors: Häußler Sophia M. , Szczepek Agnieszka J. , Gräbel Stefan , Senger Carolin , Löbel Franziska , Kufeld Markus , Olze Heidi
Published: December 2021

Severe sensorineural hearing loss can be a symptom of the benign tumor vestibular schwannoma (VS). The treatment of VS with non-invasive stereotactic radiosurgery (SRS) offers a high local tumor control rate and an innovative possibility of sequential hearing rehabilitation with cochlear implantation. This study evaluated the feasibility, complications, and auditory outcomes of such a therapeutic approach. Three males and one female (mean age 65.3 ± 9.4 years) scheduled for cochlear implantation and diagnosed with sporadic VS classified as T1 or T2 (according to Samii) were enrolled in this study. All patients had progressive hearing loss qualifying them for cochlear implantation. First, the tumor was treated using CyberKnife SRS. Next, sequential auditory rehabilitation with a cochlear implant (CI) was performed. Clinical outcomes and surgical feasibility were analyzed, and audiological results were evaluated using pure tone audiometry and speech recognition tests. All patients exhibited open-set speech understanding. The mean word recognition score (at 65 dB SPL, Freiburg Monosyllabic Test, FMT) improved after cochlear implantation in all four patients from 5.0 ± 10% (with hearing aid) preoperatively to 60.0 ± 22.7% six months postoperatively. Our results suggest that in patients with profound hearing loss caused by sporadic vestibular schwannoma, the tumor removal with SRS followed by cochlear implantation is an effective method of auditory rehabilitation.
Negotiation Power and the Impact of Gender Differences
Authors: Zulauf Katrin , Wagner Ralf
Published: December 2021

This study focuses on the intersection of power and gender in negotiations, which is seldom challenged in previous research. In an experiment with 72 negotiators, we consider issue authority as a proxy of power in negotiations and investigate how different power allocations affect the negotiation success. We learn that an increase in issue authority for one of the two parties does not necessarily lead to an increase in success. Especially, female negotiators rely on their negotiation power, rather than systematically improving mutual utilities. This article contributes to Emerson’s power-dependence theory, social role theory, role congruity theory, and gender role conflict theory by combining analyzing the impact of gender differences and power on the success. This study attempts to close the gap in the literature by focusing on the prospective function of gender role orientation in explaining gender differences in negotiation. The theoretical contribution is that females are not per se inferior in negotiations, but their performance decreases in scenarios of power asymmetries. On the contrary, unbalanced power decreases the likelihood of success. Negotiators cannot rely on a power advantage to increase their success.
Retinoblastoma Survival Following Primary Enucleation by AJCC Staging
Authors: Zhao Junyang , Feng Zhaoxun , Leung Gareth , Gallie Brenda L.
Published: December 2021

Primary enucleation of the eye with retinoblastoma is a widely accessible, life-saving treatment for retinoblastoma. This study evaluated the survival of patients following primary enucleation based on AJCC 8th edition staging. Included were 700 consecutive patients (700 eyes) treated with primary enucleation at 29 Chinese treatment centers between 2006 and 2015. Excluded were patients with less than one year follow-up, bilateral retinoblastoma, clinical evidence of extraocular disease at diagnosis, or prior focal or systemic therapy. The 5-year overall survival was 95.5%, and 5-year disease-specific survival (DSS) was 95.7%. Survival was better when enucleation was <26 days from diagnosis than delayed >26 days (96.1% vs. 86.9%; p = 0.017). Patients with eyes presenting with raised intraocular pressure with neovascularization and/or buphthalmos (cT3c) had worse 5-year DSS (87.1%) than those without (cT2b, 99.1%; cT3b, 98.7%; cT3d, 97.2%) (p < 0.05). The 5-year DSS based on pathological staging was pT1 (99.5%), pT2a (95.5%), pT3a (100%), pT3b (93.0%), pT3c/d (92.3%), and pT4 (40.9%). Patients with pT3 pathology who received six cycles of adjuvant chemotherapy had better 5-year DSS (97.7%) than those with no chemotherapy (88.1%; p = 0.06) and those who underwent 1–3 cycles (86.9%, p = 0.02) or 4–5 cycles (89.3%, p = 0.06). Patients with pT4 pathology who received six cycles of chemotherapy had better 5-year DSS than those with 0–5 cycles (63.6% vs. 16.7%; p = 0.02). Prompt primary enucleation yielded high long-term survival for children with retinoblastoma. The AJCC 8th edition staging is predictive of survival.
Clinical Outcomes after International Referral of Uveal Melanoma Patients for Proton Therapy
Authors: Marinkovic Marina , Pors Lennart J. , van den Berg Vincent , Peters Femke P. , Schalenbourg Ann , Zografos Leonidas , Pica Alessia , Hrbacek Jan , Van Duinen Sjoerd G. , Vu T. H. Khanh , Bleeker Jaco C. , Rasch Coen R. N. , Jager Martine J. , Luyten Gregorius P. M. , Horeweg Nanda
Published: December 2021

Objective: To assess oncological and ophthalmological outcomes after international referral of uveal melanoma patients for proton therapy. Materials and Methods: This is a retrospective study among Dutch uveal melanoma patients who were treated in Switzerland with 60.0 CGE proton therapy (in 4 fractions) from 1987 to 2019. All patients were ineligible for brachytherapy due to tumour size and/or proximity to the optic nerve. Time-to-event analyses were performed using Kaplan–Meier’s methodology and Cox proportional hazards models. Results: There were 103 patients (104 eyes) with a median largest tumour diameter of 19 mm (range 6–26 mm). Tumours were localised centrally (11%), mid-peripherally (65%) or peripherally (34%). Median follow-up was 7 years. Five-year local control, distant metastasis-free survival and eye preservation rates were 94%, 70% and 81% respectively. At five years, severe, moderate and mild visual impairment was observed in respectively 79%, 4% and 6% of the patients. Larger tumour volumes and more central tumour localisation were associated with severe visual impairment. After correction for these factors, dose to the macula, optic disc and retina, but not optic nerve was significantly associated with severe visual impairment. Conclusion: International referral for proton therapy yielded good tumour control and eye preservation rates, but risk of distant metastasis and severe visual impairment were substantial, possibly due to the selection of advanced tumour stages and/or central localisation. Dose to the macula may be more relevant than dose to the optic nerve for preservation of visual acuity, which is relevant for the treatment planning of proton therapy.
Advances in the Aetiology & Endoscopic Detection and Management of Early Gastric Cancer
Authors: Kohoutova Darina , Banks Matthew , Bures Jan
Published: December 2021

The mortality rates of gastric carcinoma remain high, despite the progress in research and development in disease mechanisms and treatment. Therefore, recognition of gastric precancerous lesions and early neoplasia is crucial. Two subtypes of sporadic gastric cancer have been recognized: cardia subtype and non-cardia (distal) subtype, the latter being more frequent and largely associated with infection of Helicobacter pylori, a class I carcinogen. Helicobacter pylori initiates the widely accepted Correa cascade, describing a stepwise progression through precursor lesions from chronic inflammation to gastric atrophy, gastric intestinal metaplasia and neoplasia. Our knowledge on He-licobacter pylori is still limited, and multiple questions in the context of its contribution to the pathogenesis of gastric neoplasia are yet to be answered. Awareness and recognition of gastric atrophy and intestinal metaplasia on high-definition white-light endoscopy, image-enhanced endoscopy and magnification endoscopy, in combination with histology from the biopsies taken accurately according to the protocol, are crucial to guiding the management. Standard indications for endoscopic resections (endoscopic mucosal resection and endoscopic submucosal dissection) of gastric dysplasia and intestinal type of gastric carcinoma have been recommended by multiple societies. Endoscopic evaluation and surveillance should be offered to individuals with an inherited predisposition to gastric carcinoma.
Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia
Authors: Susanti Susanti , Wibowo Satrio , Akbariani Gilang , Yoshuantari Naomi , Heriyanto Didik Setyo , Ridwanuloh Asep Muhamad , Hariyatun Hariyatun , Handaya Adeodatus Yuda , Kurnianda Johan , Hutajulu Susanna Hilda , Ilyas Mohammad
Published: December 2021

There is about three times higher incidence of young patients <50 years old with colorectal cancer, termed EOCRC, in Indonesia as compared to Europe, the UK and USA. The aim of this study was to investigate the frequency of Lynch Syndrome (LS) in Indonesian CRC patients. The previously described Nottingham Lynch Syndrome Test (N_LyST) was used in this project. N_LyST is a robust high-resolution melting (HRM)-based test that has shown 100% concordance with standard reference methods, including capillary electrophoresis and Sanger sequencing. The test consisted of five mononucleotide microsatellite markers (BAT25, BAT26, BCAT25, MYB, EWSR1), BRAF V600E mutation and MLH1 region C promoter for methylation (using bisulphite-modified DNA). A total of 231 archival (2016–2019) formalin-fixed, paraffin-embedded (FFPE) tumour tissues from CRC patients collected from Dr. Sardjito General Hospital Yogyakarta, Indonesia, were successfully tested and analysed. Among those, 44/231 (19.05%) were MSI, 25/231 (10.82%) were harbouring BRAF V600E mutation and 6/231 (2.60%) had MLH1 promoter methylation. Almost all—186/197 (99.45%)—MSS cases were MLH1 promoter unmethylated, while there were only 5/44 (11.36%) MSI cases with MLH1 promoter methylation. Similarly, only 9/44 (20.45%) of MSI cases were BRAF mutant. There were 50/231 (21.65%) EOCRC cases, with 15/50 (30%) regarded as MSI, as opposed to 29/181 (16.02%) within the older group. In total, 32/231 patients (13.85%) were classified as “Probable Lynch” (MSI, BRAF wildtype and MLH1 promoter unmethylated), which were enriched in EOCRC as compared to older patients (24% vs. 11.05%, p = 0.035). Nonetheless, 30/50 (76.00%) cases among the EOCRC cases were non-LS (sporadic) and were significantly associated with a left-sided tumour. The overall survival of both “Probable Lynch” and non-LS (sporadic) groups (n = 227) was comparable (p = 0.59), with follow up period of 0–1845 days/61.5 months. Stage, node status, histological grading and ECOG score were significantly associated with patient overall survival (p < 0.005), yet only ECOG was an independent factor for OS (HR: 4.38; 95% CI: 1.72–11.2; p = 0.002). In summary, this study is the first to reveal a potentially higher frequency of LS among CRC patients in Indonesia, which may partially contribute to the reported much higher number of EOCRC as compared to the incidence in the West.
Therapeutic Targets in Diffuse Midline Gliomas—An Emerging Landscape
Authors: Hayden Elisha , Holliday Holly , Lehmann Rebecca , Khan Aaminah , Tsoli Maria , Rayner Benjamin S. , Ziegler David S.
Published: December 2021

Diffuse midline gliomas (DMGs) are invariably fatal pediatric brain tumours that are inherently resistant to conventional therapy. In recent years our understanding of the underlying molecular mechanisms of DMG tumorigenicity has resulted in the identification of novel targets and the development of a range of potential therapies, with multiple agents now being progressed to clinical translation to test their therapeutic efficacy. Here, we provide an overview of the current therapies aimed at epigenetic and mutational drivers, cellular pathway aberrations and tumor microenvironment mechanisms in DMGs in order to aid therapy development and facilitate a holistic approach to patient treatment.
Urine-Based Metabolomics and Machine Learning Reveals Metabolites Associated with Renal Cell Carcinoma Stage
Authors: Bifarin Olatomiwa O. , Gaul David A. , Sah Samyukta , Arnold Rebecca S. , Ogan Kenneth , Master Viraj A. , Roberts David L. , Bergquist Sharon H. , Petros John A. , Edison Arthur S. , Fernández Facundo M.
Published: December 2021

Urine metabolomics profiling has potential for non-invasive RCC staging, in addition to providing metabolic insights into disease progression. In this study, we utilized liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR), and machine learning (ML) for the discovery of urine metabolites associated with RCC progression. Two machine learning questions were posed in the study: Binary classification into early RCC (stage I and II) and advanced RCC stages (stage III and IV), and RCC tumor size estimation through regression analysis. A total of 82 RCC patients with known tumor size and metabolomic measurements were used for the regression task, and 70 RCC patients with complete tumor-nodes-metastasis (TNM) staging information were used for the classification tasks under ten-fold cross-validation conditions. A voting ensemble regression model consisting of elastic net, ridge, and support vector regressor predicted RCC tumor size with a R2 value of 0.58. A voting classifier model consisting of random forest, support vector machines, logistic regression, and adaptive boosting yielded an AUC of 0.96 and an accuracy of 87%. Some identified metabolites associated with renal cell carcinoma progression included 4-guanidinobutanoic acid, 7-aminomethyl-7-carbaguanine, 3-hydroxyanthranilic acid, lysyl-glycine, glycine, citrate, and pyruvate. Overall, we identified a urine metabolic phenotype associated with renal cell carcinoma stage, exploring the promise of a urine-based metabolomic assay for staging this disease.
Radiolabeled PSMA Inhibitors
Authors: Neels Oliver C. , Kopka Klaus , Liolios Christos , Afshar-Oromieh Ali
Published: December 2021

PSMA has shown to be a promising target for diagnosis and therapy (theranostics) of prostate cancer. We have reviewed developments in the field of radio- and fluorescence-guided surgery and targeted photodynamic therapy as well as multitargeting PSMA inhibitors also addressing albumin, GRPr and integrin αvβ3. An overview of the regulatory status of PSMA-targeting radiopharmaceuticals in the USA and Europe is also provided. Technical and quality aspects of PSMA-targeting radiopharmaceuticals are described and new emerging radiolabeling strategies are discussed. Furthermore, insights are given into the production, application and potential of alternatives beyond the commonly used radionuclides for radiolabeling PSMA inhibitors. An additional refinement of radiopharmaceuticals is required in order to further improve dose-limiting factors, such as nephrotoxicity and salivary gland uptake during endoradiotherapy. The improvement of patient treatment achieved by the advantageous combination of radionuclide therapy with alternative therapies is also a special focus of this review.
miR-335 Restrains the Aggressive Phenotypes of Ovarian Cancer Cells by Inhibiting COL11A1
Authors: Wu Yi-Hui , Huang Yu-Fang , Chang Tzu-Hao , Wu Pei-Ying , Hsieh Tsung-Ying , Hsiao Sheng-Yen , Huang Soon-Cen , Chou Cheng-Yang
Published: December 2021

High collagen type XI alpha 1 (COL11A1) levels are associated with tumor progression, chemoresistance, and poor patient survival in several cancer types. MicroRNAs (miRNAs) are dysregulated in multiple cancers, including epithelial ovarian carcinoma (EOC); however, the regulation of COL11A1 by miRNAs in EOC remains unclear. We examined the role of miRNAs in regulating COL11A1 expression. We identified miR-509 and miR-335 as the candidate miRNAs through an online database search. EOC cell treatment with miR-335 mimics abrogated COL11A1 expression and suppressed cell proliferation and invasion, besides increasing the sensitivity of EOC cells to cisplatin. Conversely, treatment with miR-335 inhibitors prompted cell growth/invasiveness and chemoresistance of EOC cells. miR-335 inhibited COL11A1 transcription, thus reducing the invasiveness and chemoresistance of EOC cells via the Ets-1/MMP3 and Akt/c/EBPβ/PDK1 axes, respectively. Furthermore, it did not directly regulate PDK1 but increased PDK1 ubiquitination and degradation through COL11A1 inhibition. In vivo findings highlighted significantly decreased miR-335 mRNA expressions in EOC samples. Furthermore, patients with low miR335 levels were susceptible to advanced-stage cancer, poor response to chemotherapy, and early relapse. This study highlighted the importance of miR-335 in downregulating COL11A1-mediated ovarian tumor progression, chemoresistance, and poor survival and suggested its potential application as a therapeutic target.
Actual 10-Year Survival after Resection of Perihilar Cholangiocarcinoma: What Factors Preclude a Chance for Cure?
Authors: van Keulen Anne-Marleen , Olthof Pim , Cescon Matteo , Guglielmi Alfredo , Jarnagin William , Nadalin Silvio , Pratschke Johann , Ratti Francesca , Troisi Roberto , Groot Koerkamp Bas , Buettner Stefan , Erdmann Joris ,   on behalf of the ‘Perihilar Cholangiocarcinoma Collaboration Group’
Published: December 2021

Complete resection of perihilar cholangiocarcinoma (pCCA) is the only potentially curative treatment. Long-term survival data is rare and prognostic analyses are hindered by the rarity of the disease. This study aimed to determine the cure rate and to identify clinicopathological factors that may preclude cure. All consecutive resections for pathologically confirmed pCCA between 2000 and 2009 in 22 centers worldwide were included in a retrospective cohort study. Each center included its retrospective data series. A total of 460 patients were included with a median follow-up of 10 years for patients alive at last follow-up. Median overall survival (OS) was 29.9 months and 10-year OS was 12.8%. Twenty-nine (6%) patients reached 10-year OS. The observed cure rate was 5%. Factors that virtually precluded cure (i.e., below 1%) according to the mixture cure model included age above 70, Bismuth-Corlette type IV tumors, hepatic artery reconstruction, and positive resection margins. Cure was unlikely (i.e., below 3%) in patients with positive lymph nodes or poor tumor differentiation. These factors need to be considered in patient counseling and long-term follow-up after surgery.
Comparison of the Transcriptomic Signatures in Pediatric and Adult CML
Authors: Youn Minyoung , Smith Stephanie M. , Lee Alex Gia , Chae Hee-Don , Spiteri Elizabeth , Erdmann Jason , Galperin Ilana , Jones Lara Murphy , Donato Michele , Abidi Parveen , Bittencourt Henrique , Lacayo Norman , Dahl Gary , Aftandilian Catherine , Davis Kara L. , Matthews Jairo A. , Kornblau Steven M. , Huang Min , Sumarsono Nathan , Redell Michele S. , Fu Cecilia H. , Chen I-Ming , Alonzo Todd A. , Eklund Elizabeth , Gotlib Jason , Khatri Purvesh , Sweet-Cordero E. Alejandro , Hijiya Nobuko , Sakamoto Kathleen M.
Published: December 2021

Children with chronic myeloid leukemia (CML) tend to present with higher white blood counts and larger spleens than adults with CML, suggesting that the biology of pediatric and adult CML may differ. To investigate whether pediatric and adult CML have unique molecular characteristics, we studied the transcriptomic signature of pediatric and adult CML CD34+ cells and healthy pediatric and adult CD34+ control cells. Using high-throughput RNA sequencing, we found 567 genes (207 up- and 360 downregulated) differentially expressed in pediatric CML CD34+ cells compared to pediatric healthy CD34+ cells. Directly comparing pediatric and adult CML CD34+ cells, 398 genes (258 up- and 140 downregulated), including many in the Rho pathway, were differentially expressed in pediatric CML CD34+ cells. Using RT-qPCR to verify differentially expressed genes, VAV2 and ARHGAP27 were significantly upregulated in adult CML CD34+ cells compared to pediatric CML CD34+ cells. NCF1, CYBB, and S100A8 were upregulated in adult CML CD34+ cells but not in pediatric CML CD34+ cells, compared to healthy controls. In contrast, DLC1 was significantly upregulated in pediatric CML CD34+ cells but not in adult CML CD34+ cells, compared to healthy controls. These results demonstrate unique molecular characteristics of pediatric CML, such as dysregulation of the Rho pathway, which may contribute to clinical differences between pediatric and adult patients.
Plasma Proteome Signature to Predict the Outcome of Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
Authors: Gwark Sungchan , Ahn Hee-Sung , Yeom Jeonghun , Yu Jiyoung , Oh Yumi , Jeong Jae Ho , Ahn Jin-Hee , Jung Kyung Hae , Kim Sung-Bae , Lee Hee Jin , Gong Gyungyub , Lee Sae Byul , Chung Il Yong , Kim Hee Jeong , Ko Beom Seok , Lee Jong Won , Son Byung Ho , Ahn Sei Hyun , Kim Kyunggon , Kim Jisun
Published: December 2021

The plasma proteome of 51 non-metastatic breast cancer patients receiving neoadjuvant chemotherapy (NCT) was prospectively analyzed by high-resolution mass spectrometry coupled with nano-flow liquid chromatography using blood drawn at the time of diagnosis. Plasma proteins were identified as potential biomarkers, and their correlation with clinicopathological variables and survival outcomes was analyzed. Of 51 patients, 20 (39.2%) were HR+/HER2-, five (9.8%) were HR+/HER2+, five (9.8%) were HER2+, and 21 (41.2%) were triple-negative subtype. During a median follow-up of 52.0 months, there were 15 relapses (29.4%) and eight deaths (15.7%). Four potential biomarkers were identified among differentially expressed proteins: APOC3 had higher plasma concentrations in the pathological complete response (pCR) group, whereas MBL2, ENG, and P4HB were higher in the non-pCR group. Proteins statistically significantly associated with survival and capable of differentiating low- and high-risk groups were MBL2 and P4HB for disease-free survival, P4HB for overall survival, and MBL2 for distant metastasis-free survival (DMFS). In the multivariate analysis, only MBL2 was a consistent risk factor for DMFS (HR: 9.65, 95% CI 2.10–44.31). The results demonstrate that the proteomes from non-invasive sampling correlate with pCR and survival in breast cancer patients receiving NCT. Further investigation may clarify the role of these proteins in predicting prognosis and thus their therapeutic potential for the prevention of recurrence.
Potential to Improve Therapy of Chronic Myeloid Leukemia (CML), Especially for Patients with Older Age: Incidence, Mortality, and Survival Rates of Patients with CML in Switzerland from 1995 to 2017
Authors: Daskalakis Michael , Feller Anita , Noetzli Jasmine , Bonadies Nicolas , Arndt Volker , Baerlocher Gabriela Maria ,   The NICER Working Group
Published: December 2021

Background: Tyrosine kinase inhibitors (TKI) substantially improved chronic myeloid leukemia (CML) prognosis. We aimed to describe time period- and age-dependent outcomes by reporting real-world data of CML patients from Switzerland. Methods: Population-based incidence, mortality, and survival were assessed for four different study periods and age groups on the basis of aggregated data from Swiss Cantonal Cancer Registries. Results: A total of 1552 new CML cases were reported from 1995 to 2017. The age-standardized rate (ASR) for the incidence remained stable, while the ASR for mortality decreased by 50–80%, resulting in a five-year RS from 36% to 74% over all four age groups. Importantly, for patients <60 years (yrs), the five-year RS increased only in earlier time periods up to 92%, whereas for older patients (+80 yrs), the five-year RS continued to increase later, however, reaching only 53% until 2017. Conclusions: This is the first population-based study of CML patients in Switzerland confirming similar data compared to other population-based registries in Europe. The RS increased significantly in all age groups over the last decades after the establishment of TKI therapy. Interestingly, we found a more prominent increase in RS of patients with older age at later observation periods (45%) compared to patients at younger age (10%), implicating a greater benefit from TKI treatment for elderly occurring with delay since the establishment of TKI therapy. Our findings suggest more potential to improve CML therapy, especially for older patients.
The Costs of Complications and Unplanned Readmissions after Pancreatoduodenectomy for Pancreatic and Periampullary Tumors: Results from a Single Academic Center
Authors: Linnemann Ralph J. A. , Kooijman Bob J. L. , van der Hilst Christian S. , Sprakel Joost , Buis Carlijn I. , Kruijff Schelto , Klaase Joost M.
Published: December 2021

Background/Objectives: Complications after pancreatoduodenectomy (PD) lead to unplanned readmissions (UR), with a two- to threefold increase in admission costs. In this study, we aimed to create an understanding of the costs of complications and UR in this patient group. Furthermore, we aimed to generate a detailed cost overview that can be used to build a theoretical model to calculate the cost efficacy for prehabilitation. Methods: A retrospective cohort analysis was performed using the Dutch Pancreatic Cancer Audit (DPCA) database of patients who underwent a PD at our institute between 2013 and 2017. The total costs of the index hospital admission and UR related to the PD were collected. Results: Of the 160 patients; 35 patients (22%) had an uncomplicated course; 87 patients (54%) had minor complications, and 38 patients (24%) had severe complications. Median costs for an uncomplicated course were EUR 25.682, and for a complicated course, EUR 32.958 (p = 0.001). The median costs for minor complications were EUR 30.316, and for major complications, EUR 42.664 (p = 0.001). Costs were related to the Comprehensive Complication Index (CCI). The median costs of patients with one or more UR were EUR 41.199. Conclusions: Complications after PD led to a EUR 4.634–EUR 16.982 (18–66%) increase in hospital costs. A UR led to a cost increase of EUR 12.567 (44%). Since hospital costs are directly related to the CCI, reduction in complications will lead to cost-effectiveness.
The Transmembrane Receptor TIRC7 Identifies a Distinct Subset of Immune Cells with Prognostic Implications in Cholangiocarcinoma
Authors: Albrecht Thomas , Goeppert Benjamin , Brinkmann Fritz , Charbel Alphonse , Zhang Qiangnu , Schreck Johannes , Wilhelm Nina , Singer Stephan , Köhler Bruno C. , Springfeld Christoph , Mehrabi Arianeb , Schirmacher Peter , Kühl Anja A. , Vogel Monika N. , Jansen Holger , Utku Nalân , Roessler Stephanie
Published: December 2021

Cholangiocarcinoma (CCA) is a heterogeneous malignancy with a dismal prognosis. Therapeutic options are largely limited to surgery and conventional chemotherapy offers limited benefit. As immunotherapy has proven highly effective in various cancer types, we have undertaken a quantitative immunohistopathological assessment of immune cells expressing the immunoinhibitory T cell immune response cDNA 7 receptor (TIRC7), an emerging immunoinhibitory receptor, in a cohort of 135 CCA patients. TIRC7+ immune cells were present in both the tumor epithelia and stroma in the majority of CCA cases with the highest levels found in intrahepatic CCA. While intraepithelial density of TIRC7+ immune cells was decreased compared to matched non-neoplastic bile ducts, stromal quantity was higher in the tumor samples. Tumors exhibiting signet ring cell or adenosquamous morphology were exclusively associated with an intraepithelial TIRC7+ phenotype. Survival analysis showed intraepithelial TIRC7+ immune cell density to be a highly significant favorable prognosticator in intrahepatic but not proximal or distal CCA. Furthermore, intraepithelial TIRC7+ immune cell density correlated with the number of intraepithelial CD8+ immune cells and with the total number of CD4+ immune cells. Our results suggest the presence and prognostic relevance of TIRC7+ immune cells in CCA and warrant further functional studies on its pharmacological modulation.
Arginine Depletion in Human Cancers
Authors: Nelakurti Devi D. , Rossetti Tiffany , Husbands Aman Y. , Petreaca Ruben C.
Published: December 2021

Arginine is encoded by six different codons. Base pair changes in any of these codons can have a broad spectrum of effects including substitutions to twelve different amino acids, eighteen synonymous changes, and two stop codons. Four amino acids (histidine, cysteine, glutamine, and tryptophan) account for over 75% of amino acid substitutions of arginine. This suggests that a mutational bias, or “purifying selection”, mechanism is at work. This bias appears to be driven by C > T and G > A transitions in four of the six arginine codons, a signature that is universal and independent of cancer tissue of origin or histology. Here, we provide a review of the available literature and reanalyze publicly available data from the Catalogue of Somatic Mutations in Cancer (COSMIC). Our analysis identifies several genes with an arginine substitution bias. These include known factors such as IDH1, as well as previously unreported genes, including four cancer driver genes (FGFR3, PPP6C, MAX, GNAQ). We propose that base pair substitution bias and amino acid physiology both play a role in purifying selection. This model may explain the documented arginine substitution bias in cancers.