bluuebunny/crossref_metadata_2025 huggingface dataset:
Peri-Urbanization and Land Use Fragmentation in Mexico City. Informality, Environmental Deterioration, and Ineffective Urban Policy
Authors: Aguilar Adrian Guillermo , Flores Miguel Angel , Lara Luis Fernando
Published: March 2022

There is a great deal of concern over the scattered, fragmented expansion of cities, particularly in developing countries. This expansion accelerates the peri-urbanization processes expressed in a range of land uses, often with a concentration of the poor in peripheries with an acute shortage of services coupled with profound land-use changes, with far-reaching environmental impacts. The urban periphery is a transition zone, where the urban gradually merges into the rural landscape. It has become heterogeneous from a social, environmental, commercial, and service point of view, reproducing a model of metropolitan inequity with marked socioeconomic inequalities between the center and the periphery. The way these territories are managed is quite far from the road to sustainability. This article seeks to provide an updated analysis of the dynamics of urban expansion and land-use changes on the southern periphery of Mexico City (CDMX) in the Conservation Area (CA), to determine the extent to which a socially segregated, environmentally unsustainable model of urban fragmentation has been reinforced. It also discusses the regulatory, normative framework established in the CA, finding that it has been deficient and implemented in piecemeal fashion. It concludes that local government has failed to provide solutions to reconcile the protection of ecological conservation areas with the needs of the poor in a peri-urban area, thereby reproducing social inequalities in the city. In addition, CDMX land use policy has been ineffective in controlling the expansion of informal human settlements in peri-urban areas with high ecological value.
Helping Nature in the San Francisco Estuary Cope With Climate Change
Authors: Keeley Annika T. H. , Bush Eva , Chapple Dylan E.
Published: March 2022

Estuaries are special places that form where freshwater from the land mixes with saltwater from the ocean, which is pushed inland by the tides. This mixing creates diverse habitats that support a variety of specially adapted species. In estuaries with Mediterranean climates (similar to that of the Mediterranean region in Europe), winters are wet and summers are dry. Some winters have lots of rain, others have almost none. The animals and plants of California’s San Francisco Estuary have adapted to these variable conditions. But humans have changed how and when the water flows through the Estuary, making it tough for some species to survive. Climate change is likely to bring hotter air and water temperatures, more extreme floods and droughts, and rising sea levels, further complicating species survival. In this article, we discuss how ecosystem restoration and water management can help species survive in a changing climate.
Identification of Flux Rope Orientation via Neural Networks
Authors: Narock Thomas , Narock Ayris , Dos Santos Luiz F. G. , Nieves-Chinchilla Teresa
Published: March 2022

Geomagnetic disturbance forecasting is based on the identification of solar wind structures and accurate determination of their magnetic field orientation. For nowcasting activities, this is currently a tedious and manual process. Focusing on the main driver of geomagnetic disturbances, the twisted internal magnetic field of interplanetary coronal mass ejections (ICMEs), we explore a convolutional neural network’s (CNN) ability to predict the embedded magnetic flux rope’s orientation once it has been identified from in situ solar wind observations. Our work uses CNNs trained with magnetic field vectors from analytical flux rope data. The simulated flux ropes span many possible spacecraft trajectories and flux rope orientations. We train CNNs first with full duration flux ropes and then again with partial duration flux ropes. The former provides us with a baseline of how well CNNs can predict flux rope orientation while the latter provides insights into real-time forecasting by exploring how accuracy is affected by percentage of flux rope observed. The process of casting the physics problem as a machine learning problem is discussed as well as the impacts of different factors on prediction accuracy such as flux rope fluctuations and different neural network topologies. Finally, results from evaluating the trained network against observed ICMEs from Wind during 1995–2015 are presented.
Diverging Discourses: Animal Health Challenges and Veterinary Care in Northern Uganda
Authors: Arvidsson Anna , Fischer Klara , Hansen Kjell , Sternberg-Lewerin Susanna , Chenais Erika
Published: March 2022

People in northern Uganda are currently rebuilding their lives after a lengthy period of conflict. To facilitate this, the Ugandan government and donors have promoted investment in pigs as an important strategy for generating income quickly and ensuring livelihood security. In this context, animal health issues are an acknowledged challenge, creating uncertainty for animal owners who risk losing both their animals and income. This paper draws on policy documents guiding the veterinary sector, interviews with faculty staff at Makerere University and with veterinarians and paraprofessionals in northern Uganda, and ethnographic fieldwork in smallholder communities. The aims of this study were to contribute to an understanding of the structure of veterinary support and its dominant development narratives in policy and veterinary education and of the way in which dominant discourses and practices affect smallholders' ability to treat sick animals. Particular attention was paid to the role of paraprofessionals, here referring to actors with varied levels of training who provide animal health services mainly in rural areas. The results suggest that veterinary researchers, field veterinarians and government officials in agricultural policy share a common discourse in which making smallholders more business-minded and commercializing smallholder production are important elements in reducing rural poverty in Uganda. This way of framing smallholder livestock production overlooks other important challenges faced by smallholders in their livestock production, as well as alternative views of agricultural development. The public veterinary sector is massively under-resourced; thus while inadequately trained paraprofessionals and insufficient veterinary support currently present a risks to animal health, paraprofessionals fulfill an important role for smallholders unable to access the public veterinary sector. The dominant discourse framing paraprofessionals as “quacks” tends to downplay how important they are to smallholders by mainly highlighting the negative outcomes for animal healthcare resulting from their lack of formalized training. The conclusions of this study are that both animal health and smallholders' livelihoods would benefit from closer collaboration between veterinarians and paraprofessionals and from a better understanding of smallholders' needs.
Mean Estimation on the Diagonal of Product Manifolds
Authors: Jensen Mathias Højgaard , Sommer Stefan
Published: March 2022

Computing sample means on Riemannian manifolds is typically computationally costly, as exemplified by computation of the Fréchet mean, which often requires finding minimizing geodesics to each data point for each step of an iterative optimization scheme. When closed-form expressions for geodesics are not available, this leads to a nested optimization problem that is costly to solve. The implied computational cost impacts applications in both geometric statistics and in geometric deep learning. The weighted diffusion mean offers an alternative to the weighted Fréchet mean. We show how the diffusion mean and the weighted diffusion mean can be estimated with a stochastic simulation scheme that does not require nested optimization. We achieve this by conditioning a Brownian motion in a product manifold to hit the diagonal at a predetermined time. We develop the theoretical foundation for the sampling-based mean estimation, we develop two simulation schemes, and we demonstrate the applicability of the method with examples of sampled means on two manifolds.
Ruminal Microbial Degradation of Individual Amino Acids from Heat-Treated Soyabean Meal and Corn Gluten Meal in Continuous Culture
Authors: Gargallo Silvia , Ferret Alfred , Calsamiglia Sergio
Published: March 2022

Eight dual-flow continuous culture fermenters were used in three periods to study the effects of diets containing heat-treated soyabean meal (HSBM) or corn gluten meal (CGM) on ruminal microbial fermentation and the degradation of individual amino acids (AA). Treatments were a mix of non-protein nitrogen (N; urea and tryptone) that were progressively substituted (0, 33, 67 and 100%) for HSBM or CGM. Ruminal escape of AA was calculated with the slope ratio technique. Total volatile fatty acids (95.0 mM) and molar proportions (mol/100 mol) of acetate (59.3), propionate (21.8) and butyrate (10.5) were not affected by the treatments. As the level of HSBM or CGM increased, the concentration of ammonia-N and the degradation of protein decreased (p < 0.01), and the flows of nonammonia and dietary N increased (p < 0.01) quadratically. Compared with HSBM, CGM provided the highest flow (g/d) of total (20.6 vs. 18.3, p < 0.01), essential (9.04 vs. 8.25, p < 0.04) and nonessential (11.5 vs. 10.0, p < 0.01) AA, and increased linearly (p < 0.01) as the level of supplemental protein increased. Ruminal degradation of essential AA was higher (p < 0.04) than nonessential AA in CGM, but not in HSBM. Degradation of lysine was higher (p < 0.01) in both proteins, and degradation of methionine was higher in CGM. Ruminal degradation of individual AAs differ within and between protein sources and needs to be considered in precision feeding models.
Evaluation of Genetic Parameters of Growth of Pelibuey and Blackbelly Sheep through Pedigree in Mexico
Authors: Hernandez Víctor Rodríguez , Vega Murillo Vicente , Costa Roberto Germano , Parraguirre Lezama Conrado , Valencia de Ita Maria De Los Angeles , Romero-Arenas Omar
Published: March 2022

Birth weight (BW) and weaning weight (WW) data from Pelibuey and Blackbelly lambs belonging to the Asociación Mexicana de Criadores de Ovinos (AMCO) were used with the objective of estimating genetic parameters (heritability and genetic correlations) and analyzing the growth characteristics of ewes born and weaned at different times of the same year from different herds with pedigree registration. In the case of Pelibuey lambs, the animal model included the weaning weight at 75 days of age, considering the direct additive genetic effect, maternal additive genetic effect, covariance between direct and maternal effects, as well as the permanent environmental effect of the mother. The direct estimators of heritability for Pelibuey were BW = 0.01 ± 0.021 and WW = 0.31 ± 0.074 and for Blackbelly they were BW = 0.05 ± 0.042 and WW = 0.41 ± 0.146. In the case of the maternal heritability estimators in Pelibuey they were BW = 0.02 ± 0.040 and WW = 0.21 ± 0.121 and for Blackbelly they were BW = 0.12 ± 0.054 and WW = 0.28 ± 0.121. The magnitude of the estimates of genetic correlations between direct and maternal effects for adjusted weaning weight at 75 days of age indicate that genetic progress may be slow in a breeding program. However, these selection results could be included in the short term in the breeding programs for the Pelibuey and Blackbelly breeds in Mexico, for livestock development in low-income rural areas.
Development of Next-Generation Probiotics by Investigating the Interrelationships between Gastrointestinal Microbiota and Diarrhea in Preruminant Holstein Calves
Authors: Chuang Shih-Te , Chen Chien-Ting , Hsieh Jui-Chun , Li Kuan-Yi , Ho Shang-Tse , Chen Ming-Ju
Published: March 2022

(1) Background: We aimed to isolate and identify potential next-generation probiotics (NGP) by investigating the interrelationships between gastrointestinal microbiota and diarrhea in preruminant Holstein calves. (2) Material and methods: Twenty preruminant Holstein calves were divided into healthy and diarrheic groups after the combination outcomes of veterinary diagnosis and fecal scores. The fecal microbiome, plasma cytokines, plasma immunoglobulin (Ig) G and haptoglobin were analyzed. The potential probiotic bacteria were identified by comparing the microbiota difference between healthy and diarrheic calves and correlation analysis with fecal scores and inflammatory markers. The identified bacteria were also isolated for further evaluation for antimicrobial activities and immunoregulatory effects. (3) Results: Microbiota analysis suggested that Ruminococcaceae_UCG_014, Bifidobacterium and Pseudoflavonifractor positively correlated with bovine IgG and negatively correlated with fecal score; inflammatory factors, bovine HP, and IL-8 were classified as beneficial bacteria contributing to the health of the calves. The alternation of gut microbial composition also induced changes in the functional gene enrichment of gut microbiota in calves. The gathering of microbiomic data strongly indicated the possible beneficial effects of Bifidobacterium longum subsp. longum, expected to develop as NGP. After isolation and evaluation of the potential functionality in vitro, two specific bifidobacterial strains demonstrated antimicrobial activities and immunoregulatory effects. (4) Conclusions: The results provide a new probiotic searching approach for preventing gastrointestinal disorders in preruminant calves. Further animal study is necessary to verify the results.
A New Disease Caused by an Unidentified Etiological Agent Affects European Salamanders
Authors: Manenti Raoul , Mercurio Silvia , Melotto Andrea , Barzaghi Benedetta , Epis Sara , Tecilla Marco , Pennati Roberta , Scarì Giorgio Ulisse , Ficetola Gentile Francesco
Published: March 2022

New pathologies are causing dramatic declines and extinctions of multiple amphibian species. In 2013, in one fire salamander population of Northern Italy, we found individuals with undescribed cysts at the throat level, a malady whose existence has not previously been reported in amphibians. With the aim of describing this novel disease, we performed repeated field surveys to assess the frequency of affected salamanders from 2014 to 2020, and integrated morphological, histological, and molecular analyses to identify the pathogen. The novel disease affected up to 22% of salamanders of the study population and started spreading to nearby populations. Cysts are formed by mucus surrounding protist-like cells about 30 µm long, characterized by numerous cilia/undulipodia. Morphological and genetic analyses did not yield a clear match with described organisms. The existence of this pathogen calls for the implementation of biosecurity protocols and more studies on the dynamics of transmission and the impact on wild populations.
Pain and Pain Management in Sea Turtle and Herpetological Medicine: State of the Art
Authors: Serinelli Ilenia , Soloperto Simona , Lai Olimpia R.
Published: March 2022

In sea turtle rescue and rehabilitative medicine, many of the casualties suffer from occurrences that would be considered painful in other species; therefore, the use of analgesic drugs should be ethically mandatory to manage the pain and avoid its deleterious systemic effects to guarantee a rapid recovery and release. Nonetheless, pain assessment and management are particularly challenging in reptilians and chelonians. The available scientific literature demonstrates that, anatomically, biochemically, and physiologically, the central nervous system of reptiles and chelonians is to be considered functionally comparable to that of mammals albeit less sophisticated; therefore, reptiles can experience not only nociception but also “pain” in its definition of an unpleasant sensory and emotional experience. Hence, despite the necessity of appropriate pain management plans, the available literature on pain assessment and clinical efficacy of analgesic drugs currently in use (prevalently opioids and NSAIDs) is fragmented and suffers from some basic gaps or methodological bias that prevent a correct interpretation of the results. At present, the general understanding of the physiology of reptiles’ pain and the possibility of its reasonable treatment is still in its infancy, considering the enormous amount of information still needed, and the use of analgesic drugs is still anecdotal or dangerously inferred from other species.
A Dynamic Procedure for Time and Space Domain Based on Differential Cubature Principle
Authors: Xu Qiang , Li Hongjing , Mei Yuchen
Published: March 2022

Based on the differential cubature (DC) principle, a dynamic procedure for simultaneous discretization of time and space is developed. A spatial–temporal differential cubature analysis method for dynamic problems is established with the Timoshenko shear beam; the reliability of analysis results obtained by which is verified, and the stability of the numerical scheme is studied. This method is extended to the two-dimensional structure, and the forced vibration analysis is carried out with the thin plate as an example. The research shows that the method can acquire highly accurate numerical results, and the calculated time-history numerical solution of beam displacement is extremely consistent with the analytical solution, which can adopt to the changes in beam properties and load parameters. With fewer nodes and longer time step than the finite element method (FEM), the method in this paper can still obtain stable and accurate results when solving displacement responses of plate under forced vibration. The numerical stability of this method is closely related to the grid form and the size of time step, and the increase in the number of nodes in the time domain is conducive to increasing the stability range.
Discriminating Technique of Typhoon Rapid Intensification Trend Based on Artificial Intelligence
Authors: Zhou Guanbo , Xu Jian , Qian Qifeng , Xu Yajing , Xu Yinglong
Published: March 2022

The trend detection of the sudden change of typhoon intensity has always been a difficult issue in typhoon forecast. Artificial intelligence (AI) can implicitly extract the complex features in the images through learning a large number of samples, and it has been widely applied in the meteorological field nowadays. In this study, based on the deep residual network (ResNet) model and the long short-term memory (LSTM) model, an automatic and objective method of identifying the trend of typhoon rapid intensification (RI) is presented through marking and learning the key information on the satellite images of the typhoons on the Northwest Pacific and South China Sea from 2005 to 2018. This method introduces the typhoon lifecycle indication and can effectively forecast and identify the trend of typhoon RI. By applying the detecting method in analyzing the operational typhoon satellite cloud images in 2019, we find that the method can well capture the sudden change tendency of typhoon intensity, and the threat score of independent sample estimation in 2019 reached 0.24. In addition, four typhoon cases with RI processes from 2019 to 2021 are tested, and the results show that the AI-based identification method of typhoon RI is superior to the traditional subjective intensity prediction method, and it has important application values.
Transplantation of Human Umbilical Cord Mesenchymal Stem Cells-Derived Neural Stem Cells Pretreated with Neuregulin1β Ameliorate Cerebral Ischemic Reperfusion Injury in Rats
Authors: Zhai Qiu-Yue , Ren Yu-Qian , Ni Qin-Shuai , Song Zhen-Hua , Ge Ke-Li , Guo Yun-Liang
Published: March 2022

Ischemic stroke is a common cerebrovascular disease and recovering blood flow as early as possible is essential to reduce ischemic damage and maintain neuronal viability, but the reperfusion process usually causes additional damage to the brain tissue in the ischemic area, namely ischemia reperfusion injury. The accumulated studies have revealed that transplantation of exogenous neural stem cells (NSCs) is an ideal choice for the treatment of ischemia reperfusion injury. At present, the source and efficacy of exogenous NSCs after transplantation is still one of the key issues that need to be resolved. In this study, human umbilical cord mesenchymal stem cells (hUC-MSCs) were obtained and induced into NSCs byadding growth factor and neuregulin1β (NRG1β) was introduced during the differentiation process of NSCs. Then, the rat middle cerebral artery occlusion/reperfusion (MCAO/R) models were established, and the therapeutic effects were evaluated among groups treated by NRG1β, NSCs and NSCs pretreated with 10 nM NRG1β (NSCs-10 nM NRG1β) achieved through intra-arterial injection. Our data show that the NSCs-10 nM NRG1β group significantly improves neurobehavioral function and infarct volume after MCAO/R, as well as cerebral cortical neuron injury, ferroptosis-related indexes and mitochondrial injury. Additionally, NSCs-10 nM NRG1β intervention may function through regulating the p53/GPX4/SLC7A11 pathway, and reducing the level of ferroptosis in cells, further enhance the neuroprotective effect on injured cells.
The Yin-Yang Concept of Pediatric Obesity and Gut Microbiota
Authors: Meliț Lorena Elena , Mărginean Cristina Oana , Săsăran Maria Oana
Published: March 2022

The era of pediatric obesity is no longer a myth. Unfortunately, pediatric obesity has reached alarming incidence levels worldwide and the factors that contribute to its development have been intensely studied in multiple recent and emerging studies. Gut microbiota was recently included in the wide spectrum of factors implicated in the determination of obesity, but its role in pediatric obese patients is far from being fully understood. In terms of the infant gut microbiome, multiple factors have been demonstrated to shape its content, including maternal diet and health, type of delivery, feeding patterns, weaning and dietary habits. Nevertheless, the role of the intrauterine environment, such as the placental microbial community, cannot be completely excluded. Most studies have identified Firmicutes and Bacteroidetes as the most important players related to obesity risk in gut microbiota reflecting an increase of Firmicutes and a decrease in Bacteroidetes in the context of obesity; however, multiple inconsistencies between studies were recently reported, especially in pediatric populations, and there is a scarcity of studies performed in this age group.
Reverse Electrochemical Sensing of FLT3-ITD Mutations in Acute Myeloid Leukemia Using Gold Sputtered ZnO-Nanorod Configured DNA Biosensors
Authors: Thevendran Ramesh , Foo Kai Loong , Hussin Mohd Hazwan , Moses Emmanuel Jairaj , Citartan Marimuthu , Prasad Haarindraprasad Rajintra , Maheswaran Solayappan
Published: March 2022

Detection of genetic mutations leading to hematological malignancies is a key factor in the early diagnosis of acute myeloid leukemia (AML). FLT3-ITD mutations are an alarming gene defect found commonly in AML patients associated with high cases of leukemia and low survival rates. Available diagnostic assessments for FLT3-ITD are incapable of combining cost-effective detection platforms with high analytical performances. To circumvent this, we developed an efficient DNA biosensor for the recognition of AML caused by FLT3-ITD mutation utilizing electrochemical impedance characterization. The system was designed by adhering gold-sputtered zinc oxide (ZnO) nanorods onto interdigitated electrode (IDE) sensor chips. The sensing surface was biointerfaced with capture probes designed to hybridize with unmutated FLT3 sequences instead of the mutated FLT3-ITD gene, establishing a reverse manner of target detection. The developed biosensor demonstrated specific detection of mutated FLT3 genes, with high levels of sensitivity in response to analyte concentrations as low as 1 nM. The sensor also exhibited a stable functional life span of more than five weeks with good reproducibility and high discriminatory properties against FLT3 gene targets. Hence, the developed sensor is a promising tool for rapid and low-cost diagnostic applications relevant to the clinical prognosis of AML stemming from FLT3-ITD mutations.
Acute Cerebellar Inflammation and Related Ataxia: Mechanisms and Pathophysiology
Authors: Parvez Md. Sorwer Alam , Ohtsuki Gen
Published: March 2022

The cerebellum governs motor coordination and motor learning. Infection with external microorganisms, such as viruses, bacteria, and fungi, induces the release and production of inflammatory mediators, which drive acute cerebellar inflammation. The clinical observation of acute cerebellitis is associated with the emergence of cerebellar ataxia. In our animal model of the acute inflammation of the cerebellar cortex, animals did not show any ataxia but hyperexcitability in the cerebellar cortex and depression-like behaviors. In contrast, animal models with neurodegeneration of the cerebellar Purkinje cells and hypoexcitability of the neurons show cerebellar ataxia. The suppression of the Ca2+-activated K+ channels in vivo is associated with a type of ataxia. Therefore, there is a gap in our interpretation between the very early phase of cerebellar inflammation and the emergence of cerebellar ataxia. In this review, we discuss the hypothesized scenario concerning the emergence of cerebellar ataxia. First, compared with genetically induced cerebellar ataxias, we introduce infection and inflammation in the cerebellum via aberrant immunity and glial responses. Especially, we focus on infections with cytomegalovirus, influenza virus, dengue virus, and SARS-CoV-2, potential relevance to mitochondrial DNA, and autoimmunity in infection. Second, we review neurophysiological modulation (intrinsic excitability, excitatory, and inhibitory synaptic transmission) by inflammatory mediators and aberrant immunity. Next, we discuss the cerebellar circuit dysfunction (presumably, via maintaining the homeostatic property). Lastly, we propose the mechanism of the cerebellar ataxia and possible treatments for the ataxia in the cerebellar inflammation.
Angiogenesis Inhibitors and Immunomodulation in Renal Cell Cancers: The Past, Present, and Future
Authors: Kasherman Lawrence , Siu Derrick Ho Wai , Woodford Rachel , Harris Carole A.
Published: March 2022

Angiogenesis inhibitors have been adopted into the standard armamentarium of therapies for advanced-stage renal cell carcinomas (RCC), but more recently, combination regimens with immune checkpoint inhibitors have demonstrated better outcomes. Despite this, the majority of affected patients still eventually experience progressive disease due to therapeutic resistance mechanisms, and there remains a need to develop novel therapeutic strategies. This article will review the synergistic mechanisms behind angiogenesis and immunomodulation in the tumor microenvironment and discuss the pre-clinical and clinical evidence for both clear-cell and non-clear-cell RCC, exploring opportunities for future growth in this exciting area of drug development.
Sequestration of Intestinal Acidic Toxins by Cationic Resin Attenuates Pancreatic Cancer Progression through Promoting Autophagic Flux for YAP Degradation
Authors: Zhao Guangfu , Zhang Tianci , Liu Wei , Edderkaoui Mouad , Hu Richard , Li Jun , Pandol Stephen J. , Fu Xiangsheng , Han Yuan-Ping
Published: March 2022

Pancreatic cancer is driven by risk factors such as diabetes and chronic pancreatic injury, which are further associated with gut dysbiosis. Intestinal toxins such as bile acids and bacterial endotoxin (LPS), in excess and persistence, can provoke chronic inflammation and tumorigenesis. Of interest is that many intestinal toxins are negatively charged acidic components in essence, which prompted us to test whether oral administration of cationic resin can deplete intestinal toxins and ameliorate pancreatic cancer. Here, we found that increased plasma levels of endotoxin and bile acids in Pdx1-Cre: LSL-KrasG12D/+ mice were associated with the transformation of the pancreatic ductal carcinoma (PDAC) state. Common bile-duct-ligation or LPS injection impeded autolysosomal flux, leading to Yap accumulation and malignant transformation. Conversely, oral administration of cholestyramine to sequestrate intestinal endotoxin and bile acids resumed autolysosomal flux for Yap degradation and attenuated metastatic incidence. Conversely, chloroquine treatment impaired autolysosomal flux and exacerbated malignance, showing jeopardization of p62/ Sqxtm1 turnover, leading to Yap accumulation, which is also consistent with overexpression of cystatin A (CSTA) in situ with pancreatic cancer cells and metastatic tumor. At cellular levels, chenodeoxycholic acid or LPS treatment activated the ligand–receptor-mediated AKT-mTOR pathway, resulting in autophagy-lysosomal stress for YAP accumulation and cellular dissemination. Thus, this work indicates a potential new strategy for intervention of pancreatic metastasis through sequestration of intestinal acidic toxins by oral administration of cationic resins.
Oral Health Status in Patients with Head and Neck Cancer before Radiotherapy: Baseline Description of an Observational Prospective Study
Authors: Rupe Cosimo , Basco Alessia , Schiavelli Anna , Cassano Alessandra , Micciche’ Francesco , Galli Jacopo , Cordaro Massimo , Lajolo Carlo
Published: March 2022

(1) Background: The general hypothesis that HNC patients show compromised oral health (OH) is generally accepted, but it is not evidence-based. The objective of this baseline report of a prospective observational study was to describe the oral health of a cohort of patients with HNC at the time of dental evaluation prior to radiotherapy (RT). (2) Materials and Methods: Two hundred and thirteen patients affected by HNC who had received an indication for RT were examined with the support of orthopantomography (OPT). The DMFt of all included subjects, their periodontal status and the grade of mouth opening were recorded. (3) Results: A total of 195 patients were ultimately included: 146/195 patients (74.9%) showed poor OH (defined as having a DMFt score ≥ 13 and severe periodontitis). The following clinical characteristics were correlated with poor oral health in the univariate analysis: tumor site, smoking habit and age of the patients (in decades); χ2 test, p < 0.05. (4) Conclusions: This study confirms that the OH of HNC patients is often compromised even before the beginning of cancer treatment and, consequently, highlights how important it is to promptly schedule a dental evaluation at the moment of diagnosis of the cancer.
A Systematic Review to Define the Multi-Faceted Role of Lysine Methyltransferase SETD7 in Cancer
Authors: Monteiro Fátima Liliana , Williams Cecilia , Helguero Luisa A.
Published: March 2022

Histone–lysine N-methyltransferase SETD7 regulates a variety of cancer-related processes, in a tissue-type and signalling context-dependent manner. To date, there is no consensus regarding SETD7´s biological functions, or potential for cancer diagnostics and therapeutics. In this work, we summarised the literature on SETD7 expression and function in cancer, to identify the contexts where SETD7 expression and targeting can lead to improvements in cancer diagnosis and therapy. The most studied cancers were found to be lung and osteosarcoma followed by colorectal and breast cancers. SETD7 mRNA and/or protein expression in human cancer tissue was evaluated using public databases and/or in-house cohorts, but its prognostic significance remains inconclusive. The most studied cancer-related processes regulated by SETD7 were cell proliferation, apoptosis, epithelial-mesenchymal transition, migration and invasion with special relevance to the pRb/E2F-1 pathway. SETD7 consistently prevented epithelial to mesenchymal transition in different cancer types, and inhibition of its function appears to be associated with improved response to DNA-damaging agents in most of the analysed studies. Stabilising mutations in SETD7 target proteins prevent their methylation or promote other competing post-translational modifications that can override the SETD7 effect. This indicates that a clear discrimination of these mutations and competing signalling pathways must be considered in future functional studies.
New Directions and Challenges in Targeted Therapies of Advanced Bladder Cancer: The Role of FGFR Inhibitors
Authors: Szklener Katarzyna , Chmiel Paulina , Michalski Adam , Mańdziuk Sławomir
Published: March 2022

Bladder neoplasms, including the most common urothelial carcinoma, have been an escalating problem for years, especially in highly developed countries. Recent decades have brought us a steadily growing share of this cancer in terms of both morbidity and mortality statistics. Bladder neoplasms are not only a therapeutic challenge but also an economical one due to the demanding, costly diagnostics and treatment. The treatment of urothelial cancer can be divided depending on the stage and advancement; thus, we can distinguish three main categories: non-muscle invasive bladder cancer, conventionally treated by surgical interventions; muscle invasive bladder cancer, conventionally treated with chemotherapeutics; and advanced bladder cancer with distant metastases, conventionally treated with the intensive chemotherapy in the MVAC scheme (methotrexate, vinblastine, doxorubicin, and cisplatin). Recent years have brought a breakthrough: immunotherapy and targeted therapy were discovered to be beneficial for patients disqualified from chemotherapy or patients who progressed despite treatment. This literature review summarizes the latest research into the use of targeted therapy in the treatment of advanced bladder cancer, its benefits, and its limitations.
Comparing the Secretomes of Chemorefractory and Chemoresistant Ovarian Cancer Cell Populations
Authors: Lee Amy H. , Mejia Peña Carolina , Dawson Michelle R.
Published: March 2022

High-grade serous ovarian cancer (HGSOC) constitutes the majority of all ovarian cancer cases and has staggering rates of both refractory and recurrent disease. While most patients respond to the initial treatment with paclitaxel and platinum-based drugs, up to 25% do not, and of the remaining that do, 75% experience disease recurrence within the subsequent two years. Intrinsic resistance in refractory cases is driven by environmental stressors like tumor hypoxia which alter the tumor microenvironment to promote cancer progression and resistance to anticancer drugs. Recurrent disease describes the acquisition of chemoresistance whereby cancer cells survive the initial exposure to chemotherapy and develop adaptations to enhance their chances of surviving subsequent treatments. Of the environmental stressors cancer cells endure, exposure to hypoxia has been identified as a potent trigger and priming agent for the development of chemoresistance. Both in the presence of the stress of hypoxia or the therapeutic stress of chemotherapy, cancer cells manage to cope and develop adaptations which prime populations to survive in future stress. One adaptation is the modification in the secretome. Chemoresistance is associated with translational reprogramming for increased protein synthesis, ribosome biogenesis, and vesicle trafficking. This leads to increased production of soluble proteins and extracellular vesicles (EVs) involved in autocrine and paracrine signaling processes. Numerous studies have demonstrated that these factors are largely altered between the secretomes of chemosensitive and chemoresistant patients. Such factors include cytokines, growth factors, EVs, and EV-encapsulated microRNAs (miRNAs), which serve to induce invasive molecular, biophysical, and chemoresistant phenotypes in neighboring normal and cancer cells. This review examines the modifications in the secretome of distinct chemoresistant ovarian cancer cell populations and specific secreted factors, which may serve as candidate biomarkers for aggressive and chemoresistant cancers.
PARP Inhibitors Resistance: Mechanisms and Perspectives
Authors: Giudice Elena , Gentile Marica , Salutari Vanda , Ricci Caterina , Musacchio Lucia , Carbone Maria Vittoria , Ghizzoni Viola , Camarda Floriana , Tronconi Francesca , Nero Camilla , Ciccarone Francesca , Scambia Giovanni , Lorusso Domenica
Published: March 2022

PolyADP-ribose polymerase (PARP) inhibitors (PARPis) represent the first clinically approved drugs able to provoke “synthetic lethality” in patients with homologous recombination-deficient (HRD) tumors. Four PARPis have just received approval for the treatment of several types of cancer. Besides, another three additional PARPis underlying the same mechanism of action are currently under investigation. Despite the success of these targeted agents, the increasing use of PARPis in clinical practice for the treatment of different tumors raised the issue of PARPis resistance, and the consequent disease relapse and dismal prognosis for patients. Several mechanisms of resistance have been investigated, and ongoing studies are currently focusing on strategies to address this challenge and overcome PARPis resistance. This review aims to analyze the mechanisms underlying PARPis resistance known today and discuss potential therapeutic strategies to overcome these processes of resistance in the future.
Distinct and Common Features of Numerical and Structural Chromosomal Instability across Different Cancer Types
Authors: Zhang Xiaoxiao , Kschischo Maik
Published: March 2022

A large proportion of tumours is characterised by numerical or structural chromosomal instability (CIN), defined as an increased rate of gaining or losing whole chromosomes (W-CIN) or of accumulating structural aberrations (S-CIN). Both W-CIN and S-CIN are associated with tumourigenesis, cancer progression, treatment resistance and clinical outcome. Although W-CIN and S-CIN can co-occur, they are initiated by different molecular events. By analysing tumour genomic data from 33 cancer types, we show that the majority of tumours with high levels of W-CIN underwent whole genome doubling, whereas S-CIN levels are strongly associated with homologous recombination deficiency. Both CIN phenotypes are prognostic in several cancer types. Most drugs are less efficient in high-CIN cell lines, but we also report compounds and drugs which should be investigated as targets for W-CIN or S-CIN. By analysing associations between CIN and bio-molecular entities with pathway and gene expression levels, we complement gene signatures of CIN and report that the drug resistance gene CKS1B is strongly associated with S-CIN. Finally, we propose a potential copy number-dependent mechanism to activate the PI3K pathway in high-S-CIN tumours.
A Novel Framework for the Optimization of Simultaneous ThermoBrachyTherapy
Authors: Androulakis Ioannis , Mestrom Rob M. C. , Christianen Miranda E. M. C. , Kolkman-Deurloo Inger-Karine K. , van Rhoon Gerard C.
Published: March 2022

In high-dose-rate brachytherapy (HDR-BT) for prostate cancer treatment, interstitial hyperthermia (IHT) is applied to sensitize the tumor to the radiation (RT) dose, aiming at a more efficient treatment. Simultaneous application of HDR-BT and IHT is anticipated to provide maximum radiosensitization of the tumor. With this rationale, the ThermoBrachyTherapy applicators have been designed and developed, enabling simultaneous irradiation and heating. In this research, we present a method to optimize the three-dimensional temperature distribution for simultaneous HDR-BT and IHT based on the resulting equivalent physical dose (EQDphys) of the combined treatment. First, the temperature resulting from each electrode is precomputed. Then, for a given set of electrode settings and a precomputed radiation dose, the EQDphys is calculated based on the temperature-dependent linear-quadratic model. Finally, the optimum set of electrode settings is found through an optimization algorithm. The method is applied on implant geometries and anatomical data of 10 previously irradiated patients, using reported thermoradiobiological parameters and physical doses. We found that an equal equivalent dose coverage of the target can be achieved with a physical RT dose reduction of 20% together with a significantly lower EQDphys to the organs at risk (p-value < 0.001), even in the least favorable scenarios. As a result, simultaneous ThermoBrachyTherapy could lead to a relevant therapeutic benefit for patients with prostate cancer.
Imaging of Oligometastatic Disease
Authors: Vietti Violi Naik , Hajri Rami , Haefliger Laura , Nicod-Lalonde Marie , Villard Nicolas , Dromain Clarisse
Published: March 2022

Oligometastatic disease (OMD) is an emerging state of disease with limited metastatic tumor burden. It should be distinguished from polymetastatic disease due the potential curative therapeutic options of OMD. Imaging plays a pivotal role in the diagnosis and follow-up of patients with OMD. The imaging tools needed in the case of OMD will differ according to different parameters, which include primary tumor type, timing between measurement and treatment, potential metastatic location and the patient’s individual risk for metastasis. In this article, OMD is defined and the use of different imaging modalities in several oncologic situations are described in order to better understand OMD and its specific implication for radiologists.
Successful Pregnancies, Births, and Children Development Following Oocyte Cryostorage in Female Cancer Patients During 25 Years of Fertility Preservation
Authors: Porcu Eleonora , Cipriani Linda , Dirodi Maria , De Iaco Pierandrea , Perrone Anna Myriam , Zinzani Pier Luigi , Taffurelli Mario , Zamagni Claudio , Ciotti Patrizia Maria , Notarangelo Leonardo , Calza Nilla , Damiano Giuseppe
Published: March 2022

The preservation of fertility in cancer patients is a crucial aspect of modern reproductive medicine. Amenorrhea and infertility often occur after cancer therapy, worsening the quality of life. Cryopreservation of oocytes in young cancer patients is a therapeutic option for preserving fertility. A prospective study was conducted on 508 cancer patients who underwent oocyte cryopreservation to preserve fertility between 1996 and 2021 including the COVID-19 pandemic period. Patients underwent ovarian stimulation, followed by egg retrieval, and oocytes were cryopreserved by slow freezing or vitrification. Sixty-four thawing/warming cycles were performed. Survival, fertilization, pregnancy, and birth rate over the thawing/warming cycles were obtained. The data were compared with those from a group of 1042 nononcological patients who cryopreserved supernumerary oocytes. An average of 8.8 ± 6.9 oocytes were retrieved per cycle, and 6.1 ± 4.2 oocytes were cryopreserved. With their own stored oocytes, 44 patients returned to attempt pregnancy. From a total of 194 thawed/warmed oocytes, 157 survived (80%). In total, 100 embryos were transferred in 57 transfer/cycles, and 18 pregnancies were achieved. The pregnancy rate per transfer and pregnancy rate per patient were 31% and 41%, respectively. No statistically significant differences were observed between oncological patients and nononcological patients. A total of 15 babies were born from oncological patients. Children born showed normal growth and development. One minor malformation was detected.
Biological Characterization and Clinical Relevance of Circulating Tumor Cells: Opening the Pandora’s Box of Multiple Myeloma
Authors: Garcés Juan-José , San-Miguel Jesús , Paiva Bruno
Published: March 2022

Bone marrow (BM) aspirates are the gold standard for patient prognostication and genetic characterization in multiple myeloma (MM). However, they represent an important limitation for periodic disease monitoring because they entail an aggressive procedure. Moreover, recent findings show that a single BM aspirate is unable to reflect the complex MM heterogeneity. Recent advances in flow cytometry, microfluidics, and “omics” technologies have opened Pandora’s box of MM: The detection and isolation of circulating tumor cells (CTCs) offer a promising and minimally invasive alternative for tumor assessment and metastasis study. CTCs are detectable in premalignant and active MM states, and their enumeration has strong prognostic value, to the extent that it is challenging current stratification systems. In addition, CTCs reflect with high precision both intra- and extra-medullary disease at the phenotypic, genomic, and transcriptomic levels. Despite this high resemblance between tumor clones in distinct locations, some subtle (not random) differences might shed some light on the metastatic process. Thus, it has been suggested that a hypoxic and pro-inflammatory microenvironment could induce an arrest in proliferation forcing tumor cells to recirculate. Herein, we summarize data on the characterization of MM CTCs as well as their clinical and research potential.
Failure Analysis of TEVG’s II: Late Failure and Entering the Regeneration Pathway
Authors: Rodriguez-Soto Maria A. , Riveros Alejandra , Suarez Vargas Natalia , Garcia-Brand Andres J. , Camargo Carolina Muñoz , Cruz Juan C. , Sandoval Nestor , Briceño Juan C.
Published: March 2022

Tissue-engineered vascular grafts (TEVGs) are a promising alternative to treat vascular disease under complex hemodynamic conditions. However, despite efforts from the tissue engineering and regenerative medicine fields, the interactions between the material and the biological and hemodynamic environment are still to be understood, and optimization of the rational design of vascular grafts is an open challenge. This is of special importance as TEVGs not only have to overcome the surgical requirements upon implantation, they also need to withhold the inflammatory response and sustain remodeling of the tissue. This work aims to analyze and evaluate the bio-molecular interactions and hemodynamic phenomena between blood components, cells and materials that have been reported to be related to the failure of the TEVGs during the regeneration process once the initial stages of preimplantation have been resolved, in order to tailor and refine the needed criteria for the optimal design of TEVGs.
MicroRNA Roles in Cell Reprogramming Mechanisms
Authors: Pascale Emilia , Caiazza Carmen , Paladino Martina , Parisi Silvia , Passaro Fabiana , Caiazzo Massimiliano
Published: March 2022

Cell reprogramming is a groundbreaking technology that, in few decades, generated a new paradigm in biomedical science. To date we can use cell reprogramming to potentially generate every cell type by converting somatic cells and suitably modulating the expression of key transcription factors. This approach can be used to convert skin fibroblasts into pluripotent stem cells as well as into a variety of differentiated and medically relevant cell types, including cardiomyocytes and neural cells. The molecular mechanisms underlying such striking cell phenotypes are still largely unknown, but in the last decade it has been proven that cell reprogramming approaches are significantly influenced by non-coding RNAs. Specifically, this review will focus on the role of microRNAs in the reprogramming processes that lead to the generation of pluripotent stem cells, neurons, and cardiomyocytes. As highlighted here, non-coding RNA-forced expression can be sufficient to support some cell reprogramming processes, and, therefore, we will also discuss how these molecular determinants could be used in the future for biomedical purposes.