bluuebunny/crossref_metadata_2025 huggingface dataset:
Banning Price Discrimination under Imperfect Competition: Evidence from Colombia's Broadband
Authors: Vélez-Velásquez Juan Sebastián
Published: December 2020

Economic theory is inconclusive regarding the effects of banning third-degree price discrimination under imperfect competition because they depend on how the competing firms rank their market segments. When, relative to uniform pricing, all competitors want higher prices in the same market segments, a ban on price discrimination will reduce profits and benefit some consumers at the expense of others. If, instead, some firms want to charge higher prices in segments where their competitors want to charge lower prices, price discrimination increases competition driving all prices down. In this case, forcing the firms to charge uniform prices can increase their profits and reduce consumer surplus. We use data on Colombian broadband subscriptions to estimate the demand for internet services. Estimated preferences and assumptions about competition are used to simulate a scenario in which firms lose their ability to price discriminate. Our results show large effects on consumer surplus and large effects on firms’ profits. Aggregate profits increase but the effects for individual firms are heterogeneous. The effects on consumer welfare vary by city. In most cities, a uniform price regime causes large welfare transfers from low-income households towards high-income households and in a few cities, prices in all segments rise. Poorer households respond to the increase in prices by subscribing to internet plans with slower download speed.
Una nueva mirada a los determinantes del peso infantil en la primera infancia
Authors: Salinas Viviana , Goldsmith Weil Jael
Published: December 2020

En las últimas décadas, Chile ha experimentado una triple transición demográfica, nutricional y económica.Objetivo: Explorar la relación entre peso infantil y dos aspectos del nivel socioeconómico, ingreso familiar y educación materna, estudiando el efecto de cada uno por si solo y la manera en que operan juntos para determinar el peso infantil y comparar su efecto en menores obesos y en otro estatus de peso.Sujetos y Método: Estudio de fuentes secundarias de datos obtenidos de la Encuesta Longitudinal de Primera Infancia de 2012, analizando niños y niñas entre 2 y 6 años de edad (n = 11.339). Se estimaron modelos multivariados de regresión cuantílica para el puntaje z del índice de masa corporal (zIMC).Resultados: En niños, entre 2 y 3 años, el ingreso y peso infantil tuvieron una asociación positiva, mientras que educación materna y peso infantil una negativa. Entre los 4 y 6 años, ingreso y peso infantil tuvieron una asociación negativa entre hijos de madres con estudios superiores, pero positiva entre hijos de madres con más baja educación.Conclusión: Ingreso familiar y educación materna tienen efectos opuestos en el peso infantil. El efecto positivo de ingreso sobre zIMC es mitigado en casos de madres con altos logros educativos. Recomendamos estudiar el efecto de ingreso y educación en el peso infantil por separado e investigar los mecanismos causales que explican la relación entre determinantes socioeconómicos y peso infantil.
Rimski kamenolomi i prijevoz kamena u antičkoj Istri
Authors: Šprem Katarina
Published: December 2020

Istra se u geomorfološkom smislu kolokvijalno dijeli na Crvenu, Sivu i Bijelu. Crvena Istra proteže se južnim i zapadnim dijelom poluotoka i bogata je, kako zemljom crvenicom, tako i kvalitetnim površinskim naslagama vapnenca. To su prepoznali svojedobno i Rimljani koji su ga vadili iz nekoliko pretpostavljenih antičkih kame-noloma koji se spominju u literaturi. Nove tehnologije omogućuju otkrivanje kame -noloma koji su zarasli u vegetaciju i tako su na prvi pogled teško uočljivi. Svi su kamenolomi ucrtani na kartu u prilogu.Za iskorištavanje kamena vrlo važno je imati i dobre ceste kojim bi se taj kamen dalje prevozio do mjesta na kojem je potreban, kao na primjer za gradnju rustičnih vila ili samih prometnica. Za nešto udaljeniju distribuciju bitne su pak morske luke u kojima su se blokovi kamena mogli ukrcati na brodove. Na kartu su ucrtana dva pretpostavljena pravca pružanja antičkih prometnica čiji točan položaj danas ne znamo. Ucrtane su i sve uvale u kojima su pronađeni ostaci rimskih lučkih uređaja, kao i uvale koje su zbog svojih karakteristika mogle predstavljati pristaništa bez potrebe izgradnje lučkih uređaja. Većina se kamenoloma nalazi u blizini luka, uvala ili pristaništa, ili pak u blizini pretpostavljenoga pružanja antičkih prometnica.
Casos confirmados de dengue no Brasil entre os anos de 2008 a 2012
Authors: Facco Lucas , Madeira Laura Wanessa , Fecury Amanda Alves , Araújo Maria Helena Mendonça de , Oliveira Euzébio de , Dendasck Carla Viana , Souza Keulle Oliveira da , Dias Claudio Alberto Gellis de Mattos
Published: December 2020

A Dengue é ocasionada por um vírus de RNA, que possui 4 variações identificadas presentes no meio humano. Suas principais manifestações sintomatológicas incluem febre, dor muscular (mialgia), dor retro ocular, dor articular (artralgia), dor de cabeça (cefaleia), náuseas, vômitos e outros, como a erupção cutânea. Este artigo objetiva mostrar o número de casos confirmados de dengue no Brasil entre os anos de 2008 a 2012. No Brasil, a dengue é caracterizada como um grande problema de saúde pública, sendo uma das doenças de caráter infeccioso deveras presente. Alguns fatores, como o clima (predominantemente tropical), infraestrutura deficitária do meio urbano, além da expansão demográfica, a qual ocorre de forma desordenada, podem provocar e possivelmente justificar esse cenário nacional. Representa um grande problema de saúde pública, uma vez que o controle da doença depende do combate ao seu vetor, o qual dissemina-se com muita facilidade no país, em decorrência dos fatores climáticos e antrópicos. Para que a doença seja enfrentada de forma eficiente no país, o método mais eficaz é o combate ao vetor. O lixo e materiais devem ser separados de forma eficiente e armazenados em locais adequados para posterior reciclagem, de forma que não acumulem água e se transformem em criadouros do mosquito.
Economía circular en Ecuador: perspectivas de cumplimiento de los ODS en la era Post COVID-19
Authors: Ridaura Gregorio
Published: December 2020

INTRODUCCIÓN. La Economía Circular como perspectiva de cumplimiento de los ODS por parte de Ecuador. OBJETIVO. Análisis de las iniciativas públicas relacionadas con la promoción de la implementación de la Economía Circular en Ecuador. MÉTODO. La investigación se desarrolla bajo un enfoque de una revisión bibliográfica. RESULTADOS. Ecuador apuesta a la implementación de 12 de 17 ODS para 2030, a través de la implementación de la Estrategia Nacional de Economía Circular. DISCUSIÓN Y CONCLUSIONES. Ecuador deberá continuar hacia la definición de su Estrategia Nacional para la Economía Circular como parte de sus perspectivas de cumplimiento de los ODS en 2030.
Integrated effects of vermicompost with chemical fertilizers on the yield of mustard
Authors: Haque MA , Ali MM
Published: December 2020

Field experiments were conducted in three Agroecological zones (AEZ) at Farmer’s field, Rangpur (AEZ-3), Farmer’s field, Ishurdi (AEZ-11) and BINA farm, Mymensingh (AEZ-9) to investigate the integrated effect of vermicompost and chemical fertilizers (CF) on Mustard (Brassica napus L.) during 2017-18 cropping season to reduce the usage of chemical fertilizer for mustard cultivation. The experiments were carried out with eight treatments and three replications in Randomized Complete Block Design. The treatments for the crops used in the experiments were T1: Native soil fertility, T2:100% chemical fertilizer (CF),T3: 75% CF, T4: 75% CF + Vermicompost (VC) @ 4 t ha-1, T5:85% CF ,T6: 85% CF + VC @ 4 t ha-1 T7: 75% CF +VC @ 2 t ha-1­­­­ and T8: 85% CF+VC @ 2 tha-1. Fertilizers applied on the basis of soil test (STB). Application of vermicompost with chemical fertilizer increased the yield attributes and yields of mustard. The treatment T6 (85% CF + VC @ 4 tha-1) gave the tallest plant height, greatest number of pods plant-1 and siliqua pod-1 and maximum seed (1.82, 1.26 and 1.49 t ha-1 at Rangpur, Ishurdi and Mymensingh, respectively) and straw yields of mustard at all the location with the few exception. But the treatment T6 gave the identical results with the treatments T8, T4 and T2. Application of vermicompost also increased the N, P and K uptakes of mustard at all the location. The treatments T6 T8 and T4 gave statistically identical nutrients uptakes to the treatment T2 (100%CF). The results revealed that 75% CF with 4 t ha-1 vermicompost or 85% CF with 2 t ha-1 vermicompost almost equally effective to produce seed yield of mustard which was also comparable with the full dose (100%) of chemical fertilizers (NPKS) in all the location. Therefore 15-25% chemical fertilizer (NPKS) could be reduced either with the application of 75% CF with 4 t ha-1 vermicompost or 85% CF with 2 t ha-1 vermicompost for mustard cultivation.

Progressive Agriculture 31 (2): 81-88, 2020
Arquitectura, fotografía y redes sociales
Authors: Vergara Muñoz Jaime , Monedero Miguel Martínez
Published: December 2020

Para un arquitecto la fotografía ha sido siempre un buen instrumento de trabajo. La cámara es el vehículo por el que se establece la relación entre el trabajo arquitectónico y el espectador. Si a esta relación se le incorpora las posibilidades que ofrecen las redes sociales, cara a difundir y colectivizar una obra, entonces nos preguntarnos ¿puede esta triple relación cambiar la forma en que entendemos la arquitectura? En este asociación encontramos aspectos muy positivos como por ejemplo la rápida difusión para presentar la arquitectura, frente a un público mucho más amplio y diverso de lo que las publicaciones tradicionales podían alcanzar. Y entre los aspectos negativos están entre otros, el peligro de que las imágenes reemplacen la experiencia directa del espacio construido.
Siberian singer
Authors: Tikhonova Elena
Published: December 2020

In this work, I want to talk about the little-known paintings of the Honored Artist of Russia Yuri Spiridonov, which were greatly influenced by his childhood and adolescence as an artist. These canvases were painted during the period of searches, in the manner of modern Art Nouveau and abstract art. He was born in Kosisty among the Dolgans, a family of reindeer breeders, which is obscure in the great outdoors of Siberia (Kozhevnikov Bay) and located on the shores of the Arctic Ocean in the territory of Anabarsky's district of the Yakut Autonomous Soviet Socialist Republic. Once he finished with school, he was admitted to the Herzen State Pedagogical University of Russia in Leningrad. Today, he lives in Yakutsk and is at the height of his creative urge. In his creative search, Yuri Spiridonov often turns to folklore and folk philosophy using a synthesis of the traditions of realism and abstraction in his works. These works show the commonality of worldview philosophy, poetics of folklore, not only of Siberian, but also of many Eurasian peoples. Using the "patchwork quilt" method in the abstract images of the "World Tree", understandable to the masses throughout almost all of Eurasia, he recreated the motives of ancient Siberia, whose inhabitants moved across the Bering Strait to North America.
Clinical performance of medical students in Korea in a whole-task emergency station in the objective structured clinical examination with a standardized patient complaining of palpitations
Authors: Park Song Yi , Kong Hyun-Hee , Kim Min-Jeong , Yoon Yoo Sang , Lee Sang-Hwa , Im Sunju , Seo Ji-Hyun
Published: December 2020

This study assessed the clinical performance of 150 third-year medicalstudents in Busan, Korea in a whole-task emergency objective structured clinical examination station that simulated a patient with palpitations visiting the emergency department. The examination was conducted from November 25 to 27, 2019. Clinical performance was assessed as the number and percentage of students who performed history-taking (HT), a physical examination (PE), an electrocardiography (ECG) study, patient education (Ed), and clinical reasoning (CR), which were items on the checklist. It was found that 18.0% of students checked the patient’s pulse, 51.3% completed an ECG study, and 57.9% explained the results to the patient. A sizable proportion (38.0%) of students did not even attempt an ECG study. In a whole-task emergency station, students showed good performance on HT and CR, but unsatisfactory results for PE, ECG study, and Ed. Clinical skills educational programs for subjected student should focus more on PE, timely diagnostic tests, and sufficient Ed.
Silicone oil: physical properties and clinical use (a literature review)
Authors: Tashmukhamedov A. A.
Published: December 2020

Introduction. In modern vitreoretinal surgery, silicone oil is used for replacing the vitreous body during vitrectomy. This surgery is performed to treat retinal detachment, proliferative retinopathy, giant retinal tears and severe eye injuries. In this regard, it seems especially relevant to provide a description of the physical characteristics of silicone oils that determine the choice of surgeons.

Purpose. To study indications for the use of silicone oil tamponade as well as possible complications associated with its use based on a literature review and own research.

Materials and methods. We analyzed literature on PubMed, eLibrary, and Medline over the past 30 years. Overall, 34 sources of literature were reviewed, including results of our own clinical studies.

Results. Literature review has shown that silicone oils are very useful as a permanent tamponade. Although gas tamponade can be used for giant retinal tear management, silicone oils are used for minimizing the risk of post-surgical bleeding and reattach detached retinas in case of severe eye injuries. One of the main issues related to the use of silicone oils is the post-surgical increase in IOP. To reduce the risk of such complication, we have proposed methods of infusion and optimal schedule of silicone oil removal.

Conclusion. Silicone oil is the optimal choice for treating most retinal diseases and improving their prognosis. An important criterion for choice of silicone oil is the time that is required for tamponade.
MEDICAL CARE FOR HEMORRHOIDS IN THE FEDERAL SUBJECTS OF RUSSIA IN 2018
Authors: Veselov A. V. , Omelyanovskiy V. V. , Moskalev A. I. , Shkurko T. V. , Serbina A. A. , Kots N. A. , Kulovskaya D. P. , Shelygin Yu. A.
Published: December 2020

AIM: to analyze basic medical care characteristics for hemorrhoidal disease (HD) in federal subjects of Russia in 2018.

MATERIALS AND METHODS: the study is based on the summary data of the annual statistical observation form «Report of the chief coloproctologist of the subject of the Russian Federation» for 2018, which includes the level of outpatient treatment for HD per 100,000 of the population, the number of outpatient coloproctologists, the number of hospitalized patients for HD, the rate of patients hospitalized for emergency indications and number of coloproctological beds.

RESULTS: in 2018 in Russia there were 304.9 outpatient visits per 100,000 thousand of the population for HD (Me=304.9; Q1=236.1; Q3=401.2). Number of coloproctologists was 0.23 per 100,000 (Me=0.23; Q1=0.13; Q3=0.32), and no correlation between these indicators was found (r=0.18; p=0.09). The hospitalization rate for HD was 36.8 (Me=36.8; Q1=30.5; Q3=44.7). There were 2.68 coloproctological beds per 100,000 (Me=2.68; Q1=1.95; Q3=3.35), and the percentage of patients with HD hospitalized in an emergency hospital was 34.0% (Me=34.0; Q1=24.0; Q3=45.0). There was no correlation between the number of patients treated in a hospital and the proportion of emergency hospitalizations in patients with hemorrhoids (r=0.1; p=0.38).

CONCLUSION: in 2018, at least half a million patients with HD have got an outpatient consultation of coloproctologist. A significant staff shortage in specialists remains, and unresolved organizational problems require further studies.
COMPARATIVE EVALUATION OF MULTIPARAMETRIC ENDORECTAL ULTRASOUND AND ENHANCED IMAGING COLONOSCOPY IN THE DIAGNOSIS OF EARLY COLORECTAL CANCER
Authors: Bogdanova E. M. , Trubacheva Yu. L. , Yugai O. M. , Chernyshov S. V. , Rybakov E. G. , Khomyakov E. A.
Published: December 2020

AIM: to compare multiparametric endorectal ultrasound (ERUS) and enhanced imaging colonoscopy in the diagnosis of early colorectal cancer.

PATIENTS AND METHODS: the study included 78 patients with epithelial rectal tumor. All the patients underwent multiparametric ERUS and colonoscopy with examination by narrow beam imaging (NBI) at optical magnification. All the patients were operated.

RESULTS: a morphological examination removed specimens revealed adenomas in 48 cases, in 19 specimens – adenocarcinomas in situ and T1, and in 11 specimens – adenocarcinomas with invasion of the muscle layer or deeper. When calculating the accuracy indicators of diagnostic methods for groups of patients with adenoma, Tis-T1 adenocarcinoma, and T2-T3 adenocarcinoma, the difference in the sensitivity and specificity of the methods in none of the presented groups did not reach the level of statistical significance (p>0.05).ROC analysis showed that ultrasound has a prognostic value comparable to colonoscopy. The area difference was 0.013 (p=0.85).

CONCLUSION: endoscopy and ultrasound have similar value in the diagnosis of malignant transformation of rectal adenomas.
EFFECTIVE BOWEL CLEANSING FOR SCREENING COLONOSCOPY
Authors: Vologzhanina L. G. , Igumnova O. A. , Petukhova I. V. , Sannikov P. K.
Published: December 2020

AIM: to assess the effectiveness and safety of sodium picosulfate for screening colonoscopy.

PATIENTS AND METHODS: the retrospective study included 299 patients at mean age of 54±14 years who had screening colonoscopy, . All patients received sodium pikosulfate for bowel cleansing. The quality of bowel cleansing was evaluated by the Boston international scale. Organoleptic and subjective sensations were also evaluated.

RESULTS: the quality of bowel cleansing was 8.5±1.0 point by Boston scale. As a result of screening colonoscopy in 96 (32.1%) patients, polyps of the rectum, sigmoid, colon and ileum were detected in 11%, 8%, 11% and 2% of cases respectively. Pathology showed that 78 (26%) patients had adenomatous polyps, 13 (4%) – adenocarcinoma. All patients reported comfortable use of the agent.

CONCLUSION: sodium picosulfate fully meets the requirements for the drug used for bowel cleansing for colonoscopy.
Sport-Specific Habitual Adaptations in Neck Kinesthetic Functions Are Related to Balance Controlling Mechanisms
Authors: Majcen Rosker Ziva , Vodicar Miha
Published: December 2020

Whilst the importance of trunk, lower and upper extremities for the efficiency of maintaining body sway is well documented, the effects of cervical spine function have been seldom investigated. Afferent information from high density proprioceptors located in the cervical spine can alter postural balance, however the effects of sport’s specific habitual adaptation on balance performance have not yet been investigated. Twenty-seven taekwondo fighters and thirty controls performed unilateral balance tasks while facing forward and during neck torsion balance test while standing on the force plate. Neck kinesthesia was measured with the Head-to-Neutral Relocation test and the Butterfly test with motion-inertial unit. Differences between balance tasks were analyzed using two-way ANOVA. Additionally, correlations between body sway parameters and neck kinesthesia were studied using Pearson correlation coefficient. No differences were found between forward facing and neck torsion balance tasks in taekwondo fighters. However, correlations were found between balance on the non-preferred leg and neck kinesthesia. On the contrary, healthy individuals presented with statistically significant differences between both balance tasks and correlations between balance and neck kinesthesia. Taekwondo fighters seem to present with habitual adaptations in balance control, that differ from non-trained individuals.
Evaluation of the Circularity of Recycled PLA Filaments for 3D Printers
Authors: Gil Muñoz Victor , Muneta Luisa M. , Carrasco-Gallego Ruth , de Juanes Marquez Juan , Hidalgo-Carvajal David
Published: December 2020

The circular economy model offers great opportunities to companies, as it not only allows them to capture additional value from their products and materials, but also reduce the fluctuations of price-related risks and material supply. These risks are present in all kind of businesses not based on the circular economy. The circular economy also enables economic growth without the need for more resources. This is because each unit has a higher value as a result of recycling and reuse of products and materials after use. Following this circular economics framework, the Polytechnic University of Madrid (Universidad Politécnica de Madrid, UPM) has adopted strategies aimed at improving the circularity of products. In particular, this article provides the result of obtaining recycled PLA filament from waste originating from university 3D FFF (fused filament fabrication) printers and waste generated by “Coronamakers” in the production of visors and parts for PPEs (Personal Protective Equipment) during the lockdown period of COVID-19 in Spain. This filament is used in the production of 3D printed parts that university students use in their classes, so the circular loop is closed. The obtained score of Material Circularity Indicator (MCI) of this material has been calculated, indicating its high level of circularity.
S-adenosyl-l-homocysteine Hydrolase: A Structural Perspective on the Enzyme with Two Rossmann-Fold Domains
Authors: Brzezinski Krzysztof
Published: December 2020

S-adenosyl-l-homocysteine hydrolase (SAHase) is a major regulator of cellular methylation reactions that occur in eukaryotic and prokaryotic organisms. SAHase activity is also a significant source of l-homocysteine and adenosine, two compounds involved in numerous vital, as well as pathological processes. Therefore, apart from cellular methylation, the enzyme may also influence other processes important for the physiology of particular organisms. Herein, presented is the structural characterization and comparison of SAHases of eukaryotic and prokaryotic origin, with an emphasis on the two principal domains of SAHase subunit based on the Rossmann motif. The first domain is involved in the binding of a substrate, e.g., S-adenosyl-l-homocysteine or adenosine and the second domain binds the NAD+ cofactor. Despite their structural similarity, the molecular interactions between an adenosine-based ligand molecule and macromolecular environment are different in each domain. As a consequence, significant differences in the conformation of d-ribofuranose rings of nucleoside and nucleotide ligands, especially those attached to adenosine moiety, are observed. On the other hand, the chemical nature of adenine ring recognition, as well as an orientation of the adenine ring around the N-glycosidic bond are of high similarity for the ligands bound in the substrate- and cofactor-binding domains.
School Failure in a Girl with Specific Learning Difficulties, Suffering from Childhood Depression: Interdisciplinary Therapeutic Approach
Authors: Tatsiopoulou Paraskevi , Porfyri Georgia-Nektaria , Bonti Eleni , Diakogiannis Ioannis
Published: December 2020

Introduction: Recent studies confirm the association of literacy difficulties with higher risk of both childhood behavioral and mental disorders. When co-morbid problems occur, it is likely that each will require separate treatment. The management of major depressive disorder (MDD) for a 9.5 years old girl with specific learning difficulties (SLD), a protracted clinical course, and a family history of affective disorders, was challenging for the interdisciplinary team of our clinic, dealing with learning disabilities. Aim: The research and examination of the first-onset major depressive disorder (MDD) in a child with specific learning disabilities and its impact on school performance. This case report examines the potential contributory factors, but also the recent evidence on the co-morbidity between literacy difficulties and mental illnesses in children. Method: Reporting a two years follow-up of a 9.5 years old child with SLD suffering from childhood depression. Results: A 9.5 years old child with no history of affective disorders, but with a family history of first-degree and second-degree relative suffering from childhood-onset, recurrent, bipolar or psychotic depression. The child was assessed by a child psychiatrist during a period of 2 years, with an average of follow-ups between 1 or 2 weeks. The discussion highlights diagnostic and treatment pitfalls, as well as developmental issues. Practical interventions are suggested. Conclusion: A psychiatrically charged familial environment, including a mother suffering from anxiety disorder and behavioral disorder, contribute significantly to the development of depression in early age. An early medical intervention would be the key for successful treatment. The combination of psychotherapy and antidepressants (mostly selective serotonin reuptake inhibitors (SSRIs)) is the suggested therapy for childhood MDD.
Nanostructured Graphene Oxide-Based Hybrids as Anodes for Lithium-Ion Batteries
Authors: Sehrawat Poonam , Abid Abid , Islam Saikh S. , Mauger Alain , Julien Christian M.
Published: December 2020

Presently, the negative electrodes of lithium-ion batteries (LIBs) are constituted by carbon-based materials, which exhibit a limited specific capacity 372 mAh g−1 associated with the cycle in the composition between C and LiC6. Therefore, many efforts are currently made towards the technological development of nanostructured graphene materials because of their extraordinary mechanical, electrical, and electrochemical properties. Recent progress on advanced hybrids based on graphene oxide (GO) and reduced graphene oxide (rGO) has demonstrated the synergistic effects between graphene and an electroactive material (silicon, germanium, metal oxides (MOx)) as electrode for electrochemical devices. In this review, attention is focused on advanced materials based on GO and rGO and their composites used as anode materials for lithium-ion batteries.
Position of Circulating Tumor Cells in the Clinical Routine in Prostate Cancer and Breast Cancer Patients
Authors: Theil Gerit , Fornara Paolo , Bialek Joanna
Published: December 2020

Prostate cancer and breast cancer are the most common cancers worldwide. Anti-tumor therapies are long and exhaustive for the patients. The real-time monitoring of the healing progression could be a useful tool to evaluate therapeutic response. Blood-based biosources like circulating tumor cells (CTCs) may offer this opportunity. Application of CTCs for the clinical diagnostics could improve the sequenced screening, provide additional valuable information of tumor dynamics, and help personalized management for the patients. In the past decade, CTCs as liquid biopsy (LB) has received tremendous attention. Many different isolation and characterization platforms are developed but the clinical validation is still missing. In this review, we focus on the clinical trials of circulating tumor cells that have the potential to monitor and stratify patients and lead to implementation into clinical practice.
Stroma Transcriptomic and Proteomic Profile of Prostate Cancer Metastasis Xenograft Models Reveals Prognostic Value of Stroma Signatures
Authors: Karkampouna Sofia , De Filippo Maria , Ng Charlotte , Klima Irena , Zoni Eugenio , Spahn Martin , Stein Frank , Haberkant Per , Thalmann George , Kruithof-de Julio Marianna
Published: December 2020

Resistance acquisition to androgen deprivation treatment and metastasis progression are a major clinical issue associated with prostate cancer (PCa). The role of stroma during disease progression is insufficiently defined. Using transcriptomic and proteomic analyses on differentially aggressive patient-derived xenografts (PDXs), we investigated whether PCa tumors predispose their microenvironment (stroma) to a metastatic gene expression pattern. RNA sequencing was performed on the PCa PDXs BM18 (castration-sensitive) and LAPC9 (castration-resistant), representing different disease stages. Using organism-specific reference databases, the human-specific transcriptome (tumor) was identified and separated from the mouse-specific transcriptome (stroma). To identify proteomic changes in the tumor (human) versus the stroma (mouse), we performed human/mouse cell separation and subjected protein lysates to quantitative Tandem Mass Tag labeling and mass spectrometry. Tenascin C (TNC) was among the most abundant stromal genes, modulated by androgen levels in vivo and highly expressed in castration-resistant LAPC9 PDX. The tissue microarray of primary PCa samples (n = 210) showed that TNC is a negative prognostic marker of the clinical progression to recurrence or metastasis. Stroma markers of osteoblastic PCa bone metastases seven-up signature were induced in the stroma by the host organism in metastatic xenografts, indicating conserved mechanisms of tumor cells to induce a stromal premetastatic signature. A 50-gene list stroma signature was identified based on androgen-dependent responses, which shows a linear association with the Gleason score, metastasis progression and progression-free survival. Our data show that metastatic PCa PDXs, which differ in androgen sensitivity, trigger differential stroma responses, which show the metastasis risk stratification and prognostic biomarker potential.
Identification of Potential Serum Protein Biomarkers and Pathways for Pancreatic Cancer Cachexia Using an Aptamer-Based Discovery Platform
Authors: Narasimhan Ashok , Shahda Safi , Kays Joshua K. , Perkins Susan M. , Cheng Lijun , Schloss Katheryn N. H. , Schloss Daniel E. I. , Koniaris Leonidas G. , Zimmers Teresa A.
Published: December 2020

Patients with pancreatic ductal adenocarcinoma (PDAC) suffer debilitating and deadly weight loss, known as cachexia. Development of therapies requires biomarkers to diagnose, and monitor cachexia; however, no such markers are in use. Via Somascan, we measured ~1300 plasma proteins in 30 patients with PDAC vs. 11 controls. We found 60 proteins specific to local PDAC, 46 to metastatic, and 67 to presence of >5% cancer weight loss (FC ≥ |1.5|, p ≤ 0.05). Six were common for cancer stage (Up: GDF15, TIMP1, IL1RL1; Down: CCL22, APP, CLEC1B). Four were common for local/cachexia (C1R, PRKCG, ELANE, SOST: all oppositely regulated) and four for metastatic/cachexia (SERPINA6, PDGFRA, PRSS2, PRSS1: all consistently changed), suggesting that stage and cachexia status might be molecularly separable. We found 71 proteins that correlated with cachexia severity via weight loss grade, weight loss, skeletal muscle index and radiodensity (r ≥ |0.50|, p ≤ 0.05), including some known cachexia mediators/markers (LEP, MSTN, ALB) as well as novel proteins (e.g., LYVE1, C7, F2). Pathway, correlation, and upstream regulator analyses identified known (e.g., IL6, proteosome, mitochondrial dysfunction) and novel (e.g., Wnt signaling, NK cells) mechanisms. Overall, this study affords a basis for validation and provides insights into the processes underpinning cancer cachexia.
Neuroendocrine and Aggressive-Variant Prostate Cancer
Authors: Spetsieris Nicholas , Boukovala Myrto , Patsakis Georgios , Alafis Ioannis , Efstathiou Eleni
Published: December 2020

In prostate cancer, neuroendocrine (NE) differentiation may rarely present de novo or more frequently arises following hormonal therapy in patients with castration-resistant prostate cancer (CRPC). Its distinct phenotype is characterized by an aggressive clinical course, lack of responsiveness to hormonal therapies and poor prognosis. Importantly, a subset of CRPC patients exhibits an aggressive-variant disease with very similar clinical and molecular characteristics to small-cell prostate cancer (SCPC) even though tumors do not have NE differentiation. This aggressive-variant prostate cancer (AVPC) also shares the sensitivity of SCPC to platinum-based chemotherapy albeit with short-lived clinical benefit. As optimal treatment strategies for AVPC remain elusive, currently ongoing research efforts aim to enhance our understanding of the biology of this disease entity and improve treatment outcomes for our patients. This review is an overview of our current knowledge on prostate cancer with NE differentiation and AVPC, with a focus on their clinical characteristics and management, including available as well as experimental therapeutic strategies.
The Prognostic Impact of Circulating Tumour DNA in Melanoma Patients Treated with Systemic Therapies—Beyond BRAF Mutant Detection
Authors: Marsavela Gabriela , Johansson Peter A. , Pereira Michelle R. , McEvoy Ashleigh C. , Reid Anna L. , Robinson Cleo , Warburton Lydia , Khattak Muhammad A. , Meniawy Tarek M. , Amanuel Benhur , Millward Michael , Hayward Nicholas K. , Ziman Melanie R. , Gray Elin S. , Calapre Leslie
Published: December 2020

In this study, we evaluated the predictive value of circulating tumour DNA (ctDNA) to inform therapeutic outcomes in metastatic melanoma patients receiving systemic therapies. We analysed 142 plasma samples from metastatic melanoma patients prior to commencement of systemic therapy: 70 were treated with BRAF/MEK inhibitors and 72 with immunotherapies. Patient-specific droplet digital polymerase chain reaction assays were designed for ctDNA detection. Plasma ctDNA was detected in 56% of patients prior to first-line anti-PD1 and/or anti-CTLA-4 treatment. The detection rate in the immunotherapy cohort was comparably lower than those with BRAF inhibitors (76%, p = 0.0149). Decreasing ctDNA levels within 12 weeks of treatment was strongly concordant with treatment response (Cohen’s k = 0.798, p < 0.001) and predictive of longer progression free survival. Notably, a slower kinetic of ctDNA decline was observed in patients treated with immunotherapy compared to those on BRAF/MEK inhibitors. Whole exome sequencing of ctDNA was also conducted in 9 patients commencing anti-PD-1 therapy to derive tumour mutational burden (TMB) and neoepitope load measurements. The results showed a trend of high TMB and neoepitope load in responders compared to non-responders. Overall, our data suggest that changes in ctDNA can serve as an early indicator of outcomes in metastatic melanoma patients treated with systemic therapies and therefore may serve as a tool to guide treatment decisions.
Microwave Ablation Versus Radiofrequency Ablation for Treatment of Hepatocellular Carcinoma: A Meta-Analysis of Randomized Controlled Trials
Authors: Facciorusso Antonio , Abd El Aziz Mohamed A. , Tartaglia Nicola , Ramai Daryl , Mohan Babu P. , Cotsoglou Christian , Pusceddu Sara , Giacomelli Luca , Ambrosi Antonio , Sacco Rodolfo
Published: December 2020

There are limited and discordant results on the comparison between microwave ablation (MWA) and radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). This meta-analysis aims to compare the two treatments in terms of efficacy and safety, based on a meta-analysis of randomized-controlled trials (RCTs). A computerized bibliographic search was performed on the main databases throughout August 2020. The primary outcome was the complete response rate, while survival rate (at 1-, 2-, 3-, and 5-year), disease-free survival rate (at 1-, 2-, 3-, and 5-year), local and distant recurrence rate, adverse event rate, and number of treatment sessions were the secondary outcomes. Seven RCTs enrolling 921 patients were included. No difference in terms of complete response between the two treatments was observed (risk ratio (RR) 1.01, 95% CI 0.99–1.02). Survival rates were constantly similar, with RRs ranging from 1.05 (0.96–1.15) at 1 year to 0.91 (0.81–1.03) at 5 years. While local recurrence rate was similar between MWA and RFA (RR 0.70, 0.43–1.14), distant recurrence rate was significantly lower with MWA (RR 0.60, 0.39–0.92). Disease-free survival at 1, 2, and 3 years was similar between the two groups with RR 1.00 (0.96–1.04), 0.94 (0.84–1.06), and 1.06 (0.93–1.21), respectively. On the other hand, RR for disease-free survival at 5 years was significantly in favor of MWA (3.66, 1.32–42.27). Adverse event rate was similar between the two treatments (RR 1.06, 0.48–2.34), with bleeding and hematoma representing the most frequent complications. Our results indicate a similar efficacy and safety profile between the two techniques. MWA seems to decrease the rate of long-term recurrences, but this finding needs to be confirmed in further trials.
Continuing Effect of Cytokines and Toll-Like Receptor Agonists on Indoleamine-2,3-Dioxygenase-1 in Human Periodontal Ligament Stem/Stromal Cells
Authors: Behm Christian , Blufstein Alice , Gahn Johannes , Kubin Barbara , Moritz Andreas , Rausch-Fan Xiaohui , Andrukhov Oleh
Published: December 2020

Transplanted mesenchymal stem/stromal cells (MSCs) are a promising and innovative approach in regenerative medicine. Their regenerative potential is partly based upon their immunomodulatory activities. One of the most investigated immunomediators in MSCs, such as in periodontal ligament-derived MSCs (hPDLSCs), is indoleamine-2,3-dioxygenase-1 (IDO-1) which is upregulated by inflammatory stimuli, like cytokines. However, there are no data concerning continuing IDO-1 expression in hPDLSCs after the removal of inflammatory stimuli, such as cytokines and toll-like receptor (TLR) agonist-2 and TLR-3. Hence, primary hPDLSCs were stimulated with interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, TLR-2 agonist Pam3CSK4 or TLR-3 agonist Poly I/C. IDO-1 gene and protein expression and its enzymatic activity were measured up to five days after removing any stimuli. IL-1β- and TNF-α-induced IDO-1 expression and enzymatic activity decreased in a time-dependent manner after cessation of stimulation. IFN-γ caused a long-lasting effect on IDO-1 up to five days after removing IFN-γ. Both, TLR-2 and TLR-3 agonists induced a significant increase in IDO-1 gene expression, but only TLR-3 agonist induced significantly higher IDO-1 protein expression and enzymatic activity in conditioned media (CM). IDO-1 activity of Poly I/C- and Pam3CSK4-treated hPDLSCs was higher at one day after removal of stimuli than immediately after stimulation and declined to basal levels after five days. Among all tested stimuli, only IFN-γ was able to induce long-lasting IDO-1 expression and activity in hPDLSCs. The high plasticity of IDO-1 expression and its enzymatic activity in hPDLSCs due to the variable cytokine and virulence factor milieu and the temporal-dependent responsiveness of hPDLSCs may cause a highly dynamic potential of hPDLSCs to modulate immune responses in periodontal tissues.
Hydrogen Is Promising for Medical Applications
Authors: Hirano Shin-ichi , Ichikawa Yusuke , Sato Bunpei , Satoh Fumitake , Takefuji Yoshiyasu
Published: December 2020

Hydrogen (H2) is promising as an energy source for the next generation. Medical applications using H2 gas can be also considered as a clean and economical technology. Since the H2 gas based on electrolysis of water production has potential to expand the medical applications, the technology has been developed in order to safely dilute it and to supply it to the living body by inhalation, respectively. H2 is an inert molecule which can scavenge the highly active oxidants including hydroxyl radical (·OH) and peroxynitrite (ONOO−), and which can convert them into water. H2 is clean and causes no adverse effects in the body. The mechanism of H2 is different from that of traditional drugs because it works on the root of many diseases. Since H2 has extensive and various effects, it may be called a “wide spectrum molecule” on diseases. In this paper, we reviewed the current medical applications of H2 including its initiation and development, and we also proposed its prospective medical applications. Due to its marked efficacy and no adverse effects, H2 will be a next generation therapy candidate for medical applications.
Characterization and Wear Response of Magnetron Sputtered W–B and W–Ti–B Coatings on WC–Co Tools
Authors: Radziejewska Joanna , Psiuk Rafał , Mościcki Tomasz
Published: December 2020

In this work, α-WB2 and (W,Ti)B2 borides were applied as wear-resistant coatings to commercial WC–Co cutting inserts. Properties of coatings deposited by magnetron sputtering on WC–Co tools were studied. The crystal structure and chemical composition were analyzed. Vickers hardness and surface roughness were determined and wear test in semi-dry conditions was performed. The W–B and W–Ti–B coatings deposited on WC–Co substrate were smooth and very hard. However, titanium alloy W-B films with Vickers hardness of 3630 ± 260 HV0.02 were characterized by lower adhesion to the substrate, influencing the wear mechanism. Turning tests carried out on 304 stainless steel showed that the W–B film caused less wear compared to uncoated insert. Moreover, when W–B coating was applied, flank wear was reduced by 30% compared to uncoated WC–Co insert. Additionally, coating prevented chipping of the edge during cutting under test conditions. The research shows that W–B film deposited by magnetron sputtering has great potential as a coating for cutting tools for difficult-to-cut materials.
Controllable Synthesis of Nanostructured Ca-P Coating on Magnesium Alloys via Sodium Citrate Template-Assisted Hydrothermal Method and Its Corrosion Resistance
Authors: Wei Jieling , Cai Shu , Li Qianqian , Xie Yao , Bao Xiaogang , Xu Guohua
Published: December 2020

In this study, a nanostructured needle-like hydroxyapatite (HA) coating was prepared by the sodium citrate template-assisted hydrothermal method on magnesium alloy (AZ31). The influence of sodium citrate on the composition, microstructure and corrosion behavior of the coatings was studied. The results showed that with the increase in the mole ratio of Ca/sodium citrate from 1 to 13, the coating gradually changed from the needle-like morphology of HA to the flake morphology of β-tricalcium phosphate (β-TCP), which was related to the existing form of citrate in the solution and the trend of complexation reaction. When the mole ratio of Ca/sodium citrate was 1, the HA coating sample with the nano needle-like morphology had a high corrosion resistance (Rt = 235.300 ± 3.584 kΩ·cm2), which was almost 200 times that of the naked AZ31 alloy. Moreover, the corrosion rates of the Ca-P coated AZ31 alloy stabilized at about 0.55 mm/year and could provide more than 56 days of corrosion protection to the samples, which approximated the degradation rate requirement for biomaterials used as bone fixture.
Restoration Mechanisms at Moderate Temperatures for As-Cast ZK40 Magnesium Alloys Modified with Individual Ca and Gd Additions
Authors: Buzolin Ricardo Henrique , Moreno Guimaraes Leandro Henrique , Ávila Díaz Julián Arnaldo , Pereira da Silva Erenilton , Tolnai Domonkos , L. Mendis Chamini , Hort Norbert , Cavalcanti Pinto Haroldo
Published: December 2020

The deformation behaviour of as-cast ZK40 alloys modified with individual additions of Ca and Gd is investigated at 250 °C and 300 °C. Compression tests were carried out at 0.0001 s−1 and 0.001 s−1 using a modified Gleeble system during in-situ synchrotron radiation diffraction experiments. The deformation mechanisms are corroborated by post-mortem investigations using scanning electron microscopy combined with electron backscattered diffraction measurements. The restoration mechanisms in α-Mg are listed as follows: the formation of misorientation spread within α-Mg, the formation of low angle grain boundaries via dynamic recovery, twinning, as well as dynamic recrystallisation. The Gd and Ca additions increase the flow stress of the ZK40, which is more evident at 0.001 s−1 and 300 °C. Dynamic recovery is the predominant restoration mechanism in all alloys. Continuous dynamic recrystallisation only occurs in the ZK40 at 250 °C, competing with discontinuous dynamic recrystallisation. Discontinuous dynamic recrystallisation occurs for the ZK40 and ZK40-Gd. The Ca addition hinders discontinuous dynamic recrystallisation for the investigated temperatures and up to the local achieved strain. Gd addition forms a semi-continuous network of intermetallic compounds along the grain boundaries that withstand the load until their fragmentation, retarding discontinuous dynamic recrystallisation.
Reconfigurable Single-/Dual-Wideband Bandpass Filters Based on a Novel Topology
Authors: Bi Xiaokun , Guo Shaohua , Zhong Zengpei , Hong Kaidong , He Wei , Yuan Tao
Published: December 2020

Based on a new topology, a series of single-/dual-wideband bandpass filters (SWB/DWB BPFs) with reconfigurable masses of properties are presented. The proposed design starts from a dual-wideband passive filtering structure, which owns five transmission zeros in the stopbands and three transmission poles in each passband. Then, three capacitors are employed as the tuning elements. By controlling these three capacitors, DWB BPFs with different reconfigurable properties, including three independently tunable passband edges, tunable center frequency of lower passband with fixed absolute bandwidth, tunable bandwidth of lower passband with fixed center frequency, and switchable lower passband, can be realized. In addition, SWB BPF with tunable bandwidth also can be achieved by varying the inserted capacitors. For verification, a prototype with different capacitors is designed and fabricated. As the measured and simulated results agree well with each other, a simple design approach of reconfigurable SWB/DWB BPFs can be verified.
Molecular-Scale Considerations of Enhanced Oil Recovery in Shale
Authors: Mehana Mohamed , Kang Qinjun , Viswanathan Hari
Published: December 2020

With only less than 10% recovery, the primary production of hydrocarbon from shale reservoirs has redefined the energy equation in the world. Similar to conventional reservoirs, Enhanced Oil Recovery (EOR) techniques could be devised to enhance the current recovery factors. However, shale reservoirs possess unique characteristics that significantly affect the fluid properties. Therefore, we are adopting a molecular simulation approach that is well-suited to account for these effects to evaluate the performance of three different gases, methane, carbon dioxide and nitrogen, to recover the hydrocarbons from rough pore surfaces. Our hydrocarbon systems consists of either a single component (decane) or more than one component (decane and pentane). We simulated cases where concurrent and countercurrent displacement is studied. For concurrent displacement (injected fluids displace hydrocarbons towards the production region), we found that nitrogen and methane yielded similar recovery; however nitrogen exhibited a faster breakthrough. On the other hand, carbon dioxide was more effective in extracting the hydrocarbons when sufficient pressure was maintained. For countercurrent displacement (gases are injected and hydrocarbons are produced from the same direction), methane was found to be more effective, followed by carbon dioxide and nitrogen. In all cases, confinement reduced the recovery factor of all gases. This work provides insights to devise strategies to improve the current recovery factors observed in shale reservoirs.