bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Patients With Acute Cholecystitis After Percutaneous Cholecystostomy: From the Acute Stage to Definitive Surgical Treatment
Authors: Hung Yu-Liang , Sung Chang-Mu , Fu Chih-Yuan , Liao Chien-Hung , Wang Shang-Yu , Hsu Jun-Te , Yeh Ta-Sen , Yeh Chun-Nan , Jan Yi-Yin
Published: April 2021

Percutaneous cholecystostomy (PC) has become an important procedure for the treatment of acute cholecystitis (AC). PC is currently applied for patients who cannot undergo immediate laparoscopic cholecystectomy. However, the management following PC has not been well-reviewed. The efficacy of PC tubes has already been indicated, and compared to complications of other invasive biliary procedures, complications related to PC are rare. Following the resolution of AC, patients who can tolerate anesthesia and the surgical risk should undergo interval cholecystectomy to reduce the recurrence of biliary events. For patients unfit for surgery, whether owing to comorbidities, anesthesia risks, or surgical risks, expectant management may be applied; however, a high incidence of recurrence has been noted. In addition, several interesting issues, such as the indications for cholangiography via the PC tube, removal or maintenance of the PC catheter before definitive treatment, and timing of elective surgery, are all discussed in this review, and a relevant decision-making flowchart is proposed. PC is an effective and safe intervention, whether as expectant treatment or bridge therapy to definitive surgery. High-level evidence of post-PC care is still necessary to modify current practices.
Commensalism or Cross-Species Adoption? A Critical Review of Theories of Wolf Domestication
Authors: Serpell James A.
Published: April 2021

The work of archaeozoologists and molecular geneticists suggests that the domestication of the wolf (Canis lupus)—the ancestor of the domestic dog (C. familiaris)—probably occurred somewhere between 40,000 and 15,000 years ago somewhere on the Eurasian continent, perhaps in more than one location. Wolf domestication was therefore underway many millennia before the origins of agriculture and the domestication of food animals, such as sheep and goats. Currently, there are two predominant “origin stories” concerning the domestication of the wolf. The dominant narrative in recent literature is the commensal scavenger hypothesis which posits that wolves essentially domesticated themselves by invading ancient human settlements in search of animal remains and other edible waste discarded by hunter-gatherers. Over time, tolerance by humans gave a selective advantage to the bolder, less fearful wolves, which then diverged from the ancestral population as they adapted to the new scavenging niche. At some point in the process, humans also began to recognize the benefits of living with resident, semi-domestic wolves, either as guards or as hunting partners, thereby cementing the relationship. The alternative account of wolf domestication is very different. Sometimes known as the pet keeping or cross-species adoption hypothesis, this narrative draws heavily on anthropological observations of pet keeping among recent hunter-gatherers, and postulates that Paleolithic peoples were similarly inclined to capture, adopt and rear infant mammals, such as wolf pups, and that this habitual human nurturing behavior ultimately provided the basis for the evolution of a cooperative social system involving both species. This review critically examines and analyzes these two distinct domestication narratives and explores the underlying and sometimes erroneous assumptions they make about wolves, Pleistocene humans, and the original relationships that existed between the two species. The paper concludes that the commensal scavenger hypothesis is untenable based on what is known about recent and ancient hunter-gatherer societies, and that wolf domestication was predicated on the establishment of cooperative social relations between humans and wolves based on the early socialization of wolf pups.
Estrogen Aggravates Tumor Growth in a Diffuse Gastric Cancer Xenograft Model
Authors: Lee Sunyi , Kim Kyoung Mee , Lee Seung Yeon , Jung Joohee
Published: April 2021

Gastric cancer has the fifth-highest incidence rate and is the third leading cause of cancer-related deaths worldwide. The incidence of gastric cancer is higher in men than in women, but for the diffuse types of gastric cancer, the trend is opposite. Estrogen is considered the prime culprit behind these differences. Nevertheless, the action of estrogen in gastric cancers remains unclear. In this study, we investigated the effect of estrogen on diffuse-type gastric cancer. Human female diffuse gastric cancer SNU-16 cells were transplanted into male and female mice to analyze the effect of endogenous estrogen on tumor growth. Furthermore, the effect of exogenous estrogen was evaluated in ovariectomized mice. Expressed genes were compared between female and male xenograft models using RNA sequencing analysis. Furthermore, human gene expression omnibus databases were utilized to examine the effect of our target genes on overall survival. SNU-16-derived tumor growth was faster in female mice than in male mice. In total RNA sequencing, interferon gamma receptor 2 (IFNGR2), IQ motif containing E (IQCE), transient receptor potential cation channel subfamily M member 4 (TRPM4), and structure-specific endonuclease subunit SLX4 (SLX4) were found. These genes could be associated with the tumor growth in female diffuse-type gastric cancer which was affected by endogenous estrogen. In an ovariectomized gastric cancer xenograft model, exogenous estrogen promoted tumor growth. Especially, our results indicated that estrogen induced G protein-coupled estrogen receptor expression in these mice. These results suggest that estrogen aggravates tumor progression in female diffuse gastric cancer.
High Expression of Tomm34 and Its Correlations With Clinicopathology in Oral Squamous Cell Carcinoma
Authors: Cai Min , Tan Rukeng , Huang Yunyi , Chen Xuanyi , Kong Qingci , Guo Kaixin , Xu Meng
Published: April 2021

Tomm34, as a member of the outer mitochondrial membrane proteins, is evenly distributed between the cytoplasm and the outer mitochondrial membrane. It is up-regulated in a variety of tumors and correlates with poor prognosis. This study aimed to investigate expression of Tomm34 and its correlations with clinicopathology in oral squamous cell carcinoma (OSCC). Oncomine database and UALCAN database were utilized to predict the expression and prognosis values of Tomm34 in head and neck squamous cell carcinoma (HNSCC). By immunohistochemistry, a retrospective study was performed to verify the bioinformatics results to evaluate the Tomm34 expression and clinicopathological variables in both HPV-positive OSCC and HPV-negative OSCC. Immunohistochemistry of our cohort revealed that 48 cases fulfilled the Tomm34 high expression judgment criteria, and the overall positive rate was 60% (48/80), and 27 cases fulfilled the p16 expression judgment criteria (33.75%, 27/80). The high expression of Tomm34 was closely related with the TNM classification of OSCC (p < 0.01) and tumor size (p < 0.01) both in HPV-negative OSCC and HPV-positive OSCC, while related with lymph node metastasis (p = 0.001) in HPV-negative OSCC and drinking history (p = 0.044) in HPV-positive OSCC. In addition, the Kaplan-Meier curves indicated that higher level of Tomm34 was correlated with poorer overall survival (OS) and disease-free survival (DFS) in HPV-negative OSCC (OS, p = 0.046; DFS, p = 0.020) but not in HPV-positive OSCC (OS, p = 0.824; DFS, p = 0.782). In conclusion, Tomm34 is highly expressed in OSCC and may be a useful factor to provide prognostic information, especially in HPV-negative OSCC group.
A Two-Dimensional mKdV Linear Map and Its Application in Digital Image Cryptography
Authors: Zakaria La , Yuliani Endah , Asmiati Asmiati
Published: April 2021

Cryptography is the science and study of protecting data in computer and communication systems from unauthorized disclosure and modification. An ordinary difference equation (a map) can be used in encryption–decryption algorithms. In particular, the Arnold’s cat and the sine-Gordon linear maps can be used in cryptographic algorithms for encoding digital images. In this article, a two-dimensional linear mKdV map derived from an ordinary difference mKdV equation will be used in a cryptographic encoding algorithm. The proposed encoding algorithm will be compared with those generated using sine-Gordon and Arnold’s cat maps via the correlations between adjacent pixels in the encrypted image and the uniformity of the pixel distribution. Note that the mKdV map is derived from the partial discrete mKdV equation with Consistency Around the Cube (CAC) properties, whereas the sine-Gordon map is derived from the partial discrete sine-Gordon equation, which does not have CAC properties.
Research on the Physical Characteristic Parameters of Banana Bunches for the Design and Development of Postharvesting Machinery and Equipment
Authors: Guo Jie , Fu Han , Yang Zhou , Li Jun , Jiang Yinlong , Jiang Tingting , Liu Enxiu , Duan Jieli
Published: April 2021

In the operations of the banana postharvesting process, the design and development related to the dehanding machine, the cutting and crushing machine of bunch stalks, and the fiber extraction machine of bunch stalks are in the initial stages. In addition, with the development of society and urbanization, the aging populations in hilly and mountainous areas, where bananas are planted, are becoming a more and more serious problem. The basic physical characteristic parameters of banana bunches, banana hands, and bunch stalks are the basis for studying their biomechanical properties and designing and developing the corresponding mechanical equipment. We measured the diameter, thickness of rind, curvature, density, moisture content, diameter of vascular bundle, weight of bunch stalk, and axial distance and circumferential angle of Brazilian and plantain banana hands using experiments and statistical analysis. Through the combination of physical experiments and numerical statistics, we obtained the value range and changing law of the physical characteristic parameters of banana bunches.
Genetic Diversity and Population Structures in Chinese Miniature Pigs Revealed by SINE Retrotransposon Insertion Polymorphisms, a New Type of Genetic Markers
Authors: Chen Cai , Wang Xiaoyan , Zong Wencheng , D’Alessandro Enrico , Giosa Domenico , Guo Yafen , Mao Jiude , Song Chengyi
Published: April 2021

RIPs have been developed as effective genetic markers and popularly applied for genetic analysis in plants, but few reports are available for domestic animals. Here, we established 30 new molecular markers based on the SINE RIPs, and applied them for population genetic analysis in seven Chinese miniature pigs. The data revealed that the closed herd (BM-clo), inbreeding herd (BM-inb) of Bama miniature pigs were distinctly different from the BM-cov herds in the conservation farm, and other miniature pigs (Wuzhishan, Congjiang Xiang, Tibetan, and Mingguang small ear). These later five miniature pig breeds can further be classified into two clades based on a phylogenetic tree: one included BM-cov and Wuzhishan, the other included Congjiang Xiang, Tibetan, and Mingguang small ear, which was well-supported by structure analysis. The polymorphic information contents estimated by using SINE RIPs are lower than the predictions based on microsatellites. Overall, the genetic distances and breed-relationships between these populations revealed by 30 SINE RIPs generally agree with their evolutions and geographic distributions. We demonstrated the potential of SINE RIPs as new genetic markers for genetic monitoring and population structure analysis in pigs, which can even be extended to other livestock animals.
Effect of Scrapie Prion Infection in Ovine Bone Marrow-Derived Mesenchymal Stem Cells and Ovine Mesenchymal Stem Cell-Derived Neurons
Authors: García-Mendívil Laura , Mediano Diego R. , Hernaiz Adelaida , Sanz-Rubio David , Vázquez Francisco J. , Marín Belén , López-Pérez Óscar , Otero Alicia , Badiola Juan J. , Zaragoza Pilar , Ordovás Laura , Bolea Rosa , Martín-Burriel Inmaculada
Published: April 2021

Scrapie is a prion disease affecting sheep and goats and it is considered a prototype of transmissible spongiform encephalopathies (TSEs). Mesenchymal stem cells (MSCs) have been proposed as candidates for developing in vitro models of prion diseases. Murine MSCs are able to propagate prions after previous mouse-adaptation of prion strains and, although ovine MSCs express the cellular prion protein (PrPC), their susceptibility to prion infection has never been investigated. Here, we analyze the potential of ovine bone marrow-derived MSCs (oBM-MSCs), in growth and neurogenic conditions, to be infected by natural scrapie and propagate prion particles (PrPSc) in vitro, as well as the effect of this infection on cell viability and proliferation. Cultures were kept for 48–72 h in contact with homogenates of central nervous system (CNS) samples from scrapie or control sheep. In growth conditions, oBM-MSCs initially maintained detectable levels of PrPSc post-inoculation, as determined by Western blotting and ELISA. However, the PrPSc signal weakened and was lost over time. oBM-MSCs infected with scrapie displayed lower cell doubling and higher doubling times than those infected with control inocula. On the other hand, in neurogenic conditions, oBM-MSCs not only maintained detectable levels of PrPSc post-inoculation, as determined by ELISA, but this PrPSc signal also increased progressively over time. Finally, inoculation with CNS extracts seems to induce the proliferation of oBM-MSCs in both growth and neurogenic conditions. Our results suggest that oBM-MSCs respond to prion infection by decreasing their proliferation capacity and thus might not be permissive to prion replication, whereas ovine MSC-derived neuron-like cells seem to maintain and replicate PrPSc.
Assessment of Response to Moderate and High Dose Supplementation of Astaxanthin in Laying Hens
Authors: Dansou Dieudonné M. , Wang Hao , Nugroho Ramdhan D. , He Weizhao , Zhao Qingyu , Zhang Junmin
Published: April 2021

In this study, we evaluated the impact of moderate and high dose dietary supplementation of astaxanthin on production performance, quality of eggs, and health status of laying hens. The experiment involved 480 laying hens, divided into four groups of eight replicates. The different groups named A1, A2, A3, and A4 were allocated the same diet supplemented with Haematococcus pluvialis powder to provide 0, 21.3, 42.6, and 213.4 mg of astaxanthin per kilogram of feed, respectively. One-way ANOVA and linear and quadratic regression analysis were used to assess the differences between the groups. The results showed that the production performance of laying hens and the physical quality of eggs did not significantly differ between the groups (p > 0.05). Astaxanthin distribution in tissues was typical per bird, whereas the egg yolk coloration and astaxanthin concentration increased with the supplementation dose (p < 0.001). However, there was a decrease in concentration and coloration efficacy of astaxanthin at high dose supplementation (213.4 mg/kg) compared to moderate doses (21.3 and 42.6 mg/kg). Blood biochemical tests showed some discrepancies that were not ascribed to the effect of diets, and the increase in liver weight in the A4 group compared to others was equated with an adaptation of laying hens to the high dose supplementation. Astaxanthin improved superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and diminished malondialdehyde (MDA) content in both liver and serum; meanwhile, the activities of SOD and GSH-Px in serum were similar between the moderate doses and high dose supplementation. Additionally, astaxanthin alleviated interleukin 2, 4, and 6 (IL-2, IL-4, and IL-6, respectively) in serum, showing the best effect in A3 and A4 groups. Besides, immunoglobulin G and M (IgG and IgM), as well as tumor necrosis factor-alpha and beta (TNF-α and TNF-β), were not much affected. It was concluded that although astaxanthin has no obvious adverse effect on the performance and health status of laying hens, it may not be valuable for egg fortification and health status improvement of laying hens at high dose supplementation. The high dose astaxanthin supplementation up to 213.4 mg/kg in the diet might be avoided.
Effects of Sources and Forms of Vitamin K3 on Its Storage Stability in Vitamin Premixes or Vitamin Trace Mineral Premixes
Authors: Wang Huakai , Yang Pan , Li Longxian , Zhang Nan , Ma Yongxi , Xu Xuexin
Published: April 2021

Six types of vitamin K3 (VK3); two sources (menadione sodium bisulfite, MSB; menadione nicotinamide bisulfite, MNB), and three different forms (crystal, micro-capsule, and micro-sphere) were used to determine the retention of VK3 in vitamin premixes (Experiment 1) or vitamin trace mineral (VTM) premixes (Experiment 2) after 1, 2, 3, and 6 months of storage. The retention of VK3 in vitamin premixes was evaluated at 25 °C/60% relative humidity or 40 °C/75% relative humidity in an incubator in Experiment 1 and in VTM premixes (choline chloride: 0 vs. 16,000 mg/kg) stored at room temperature in Experiment 2. The VK3 retention in vitamin premix or VTM premix decreased significantly with the extension of storage time (p < 0.05). In Experiment 1, the VK3 retention was higher in the 25 °C/60% incubator (56%) than in the 40 °C/75% incubator (28%). The MNB retention (52%) was higher than MSB retention (32%). The retention of VK3 in micro-capsules (43%) or micro-spheres (48%) was higher than the crystal form (35%) after six months of storage. In Experiment 2, there was no difference between the retention of MSB (49%) or MNB (47%). The retention of VK3 of micro-capsule (51%) or micro-sphere (54%) was higher than that of crystal form (40%). The VK3 retention was higher in the choline-free group (51%) than in the choline group (47%) after six months of storage. Finally, the predicted equations of VK3 retention with storage time in vitamin premixes or VTM premixes were established. The R2 of the prediction equations was ≥0.9005, indicating that time is an important factor in predicting VK3 retention. In conclusion, the higher temperature-relative humidity, choline had negative effects on VK3 retention during premix storage. MNB retention was higher than MSB during storage of vitamin premix. The encapsulated forms of VK3, micro-capsules and micro-spheres, could improve VK3 storage stability in vitamin premix and VTM premix.
Molecular, Immunomodulatory, and Histopathological Role of Mesenchymal Stem Cells and Beetroot Extract on Cisplatin Induced Testicular Damage in Albino Rats
Authors: Hassen Marwa T. , Mohamed Hanaa K. , Montaser Metwally M. , El-Sharnouby Mohamed E. , Awad Nabil , Ebiya Rasha A.
Published: April 2021

Cisplatin (Cis) a drug commonly used as a chemotherapeutic agent to treat various types of cancer, inducing testicular damage. The present study aimed to investigate the inhibitory potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) and beetroot extract (BRE) in albino rats after testicular toxicity induced by cisplatin. Thirty adult male albino rats were grouped into: the control group, Cis group receiving a single dose of 7 mg/kg i.p. (intraperitoneal) to induce testicular toxicity, Cis plus BM-MSCs injected Cis followed by 2 × 106 of BM-MSCs; Cis plus BRE group receiving Cis followed by 300 mg/kg body weight/day of BRE, and Cis plus BM-MSCs and BRE group. In the current study, Cis reduced sperm count, serum testosterone level, and testicular activity of alkaline phosphatase (AKP), besides a marked inhibition of succinate dehydrogenase (SDH) activity. In addition, it significantly increased malondialdehyde (MDA) and along with a marked decrease in testis reduced glutathione content and total antioxidant capacity (TAC). At the same time, Cis administration resulted in a marked elevation in interleukine-6 and the iNOS and caspase-3 genes; however, it decreased the expression of steroidogenic acute regulatory protein (StAR). Combined treatment with BM-MSCs and BRE resulted in great improvement of all previous parameters. These results were also confirmed by histopathological and immunohistochemical examination. In conclusion, both MSCs and BRE were found to have potent potentials to inhibit testicular damage induced by cisplatin.
Antioxidants of Natural Products
Authors: Kim Mee Ree
Published: April 2021

Antioxidant ingredients are known to contribute to the beneficial effects of natural products in health promotion as well as disease prevention by reducing oxidative stress, caused by reactive oxygen or nitrogen species, in biological systems [...]
Six-Gear Roadmap towards the Smart Factory
Authors: Sufian Amr T. , Abdullah Badr M. , Ateeq Muhammad , Wah Roderick , Clements David
Published: April 2021

The fourth industrial revolution is the transformation of industrial manufacturing into smart manufacturing. The advancement of digital technologies that make the trend Industry 4.0 are considered as the transforming force that will enable this transformation. However, Industry 4.0 digital technologies need to be connected, integrated and used effectively to create value and to provide insightful information for data driven manufacturing. Smart manufacturing is a journey and requires a roadmap to guide manufacturing organizations for its adoption. The objective of this paper is to review different methodologies and strategies for smart manufacturing implementation to propose a simple and a holistic roadmap that will support the transition into smart factories and achieve resilience, flexibility and sustainability. A comprehensive review of academic and industrial literature was preformed based on multiple stage approach and chosen criteria to establish existing knowledge in the field and to evaluate latest trends and ideas of Industry 4.0 and smart manufacturing technologies, techniques and applications in the manufacturing industry. These criteria are sub-grouped to fit within various stages of the proposed roadmap and attempts to bridge the gap between academia and industry and contributes to a new knowledge in the literature. This paper presents a conceptual approach based on six stages. In each stage, key enabling technologies and strategies are introduced, the common challenges, implementation tips and case studies of industrial applications are discussed to potentially assist in a successful adoption. The significance of the proposed roadmap serve as a strategic practical tool for rapid adoption of Industry 4.0 technologies for smart manufacturing and to bridge the gap between the advanced technologies and their application in manufacturing industry, especially for SMEs.
Quasi-Passive Resistive Exosuit for Space Activities: Proof of Concept
Authors: Di Natali Christian , Chini Giorgia , Totaro Massimo , Lora-Millán Julio S. , Rocon Eduardo , Beccai Lucia , Caldwell Darwin G. , Visentin Gianfranco , Ortiz Jesús
Published: April 2021

The limits of space travel are continuously evolving, and this creates increasingly extreme challenges for the crew’s health that must be addressed by the scientific community. Long-term exposure to micro-gravity, during orbital flights, contributes to muscle strength degradation and increases bone density loss. In recent years, several exercise devices have been developed to counteract the negative health effects of zero-gravity on astronauts. However, the relatively large size of these devices, the need for a dedicated space and the exercise time-frame for each astronaut, does not make these devices the best choice for future long range exploration missions. This paper presents a quasi-passive exosuit to provide muscle training using a small, portable, proprioceptive device. The exosuit promotes continuous exercise, by resisting the user’s motion, during routine all-day activity. This study assesses the effectiveness of the resistive exosuit by evaluating its effects on muscular endurance during a terrestrial walking task. The experimental assessment on biceps femoris and vastus lateralis, shows a mean increase in muscular activation of about 97.8% during five repetitions of 3 min walking task at 3 km/h. The power frequency analysis shows an increase in muscular fatigue with a reduction of EMG median frequency of about 15.4% for the studied muscles.
The Influence of Large-Scale Environment on the Extremely Active Tropical Cyclone Activity in November 2019 over the Western North Pacific
Authors: Shi Mengying , Wang Sulei , Qi Xiaoxu , Zhao Haikun , Shu Yu
Published: April 2021

In November 2019, tropical cyclone (TC) frequency over the western North Pacific reached its record high. In this study, the possible causes and formation mechanisms of that record high TC frequency are investigated by analyzing the effect of large-scale environmental factors. A comparison between the extremely active TC years and extremely inactive TC years is performed to show the importance of the large-scale environment. The contributions of several dynamic and thermodynamic environmental factors are examined on the basis of two genesis potential indexes and the box difference index that can measure the relative contributions of large-scale environmental factors to the change in TC genesis frequency. Results indicate that dynamical factors played a more important role in TC genesis in November 2019 than thermodynamic factors. The main contributions were from enhanced low-level vorticity and strong upward motion accompanied by positive anomalies in local sea surface temperature, while the minor contribution was from changes in vertical wind shear. Changes in these large-scale environmental factors are possibly related to sea surface temperature anomalies over the Pacific (e.g., strong Pacific meridional mode).
Atmospheric Thermal and Dynamic Vertical Structures of Summer Hourly Precipitation in Jiulong of the Tibetan Plateau
Authors: Tang Yonglan , Xu Guirong , Wan Rong , Wang Xiaofang , Wang Junchao , Li Ping
Published: April 2021

It is an important to study atmospheric thermal and dynamic vertical structures over the Tibetan Plateau (TP) and their impact on precipitation by using long-term observation at representative stations. This study exhibits the observational facts of summer precipitation variation on subdiurnal scale and its atmospheric thermal and dynamic vertical structures over the TP with hourly precipitation and intensive soundings in Jiulong during 2013–2020. It is found that precipitation amount and frequency are low in the daytime and high in the nighttime, and hourly precipitation greater than 1 mm mostly occurs at nighttime. Weak precipitation during the daytime may be caused by air advection, and strong precipitation at nighttime may be closely related with air convection. Both humidity and wind speed profiles show obvious fluctuation when precipitation occurs, and the greater the precipitation intensity, the larger the fluctuation. Moreover, the fluctuation of wind speed is small in the morning, large at noon and largest at night, presenting a similar diurnal cycle to that of convective activity over the TP, which is conductive to nighttime precipitation. Additionally, the inverse layer is accompanied by the inverse humidity layer, and wind speed presents multi-peaks distribution in its vertical structure. Both of these are closely related with the underlying surface and topography of Jiulong. More studies on physical mechanism and numerical simulation are necessary for better understanding the atmospheric phenomenon over the TP.
Improving Wine Quality and Safety
Authors: Marangon Matteo , Kallithraka Stamatina
Published: April 2021

Wine is a product that can be characterized both as a commodity but also as a luxury, depending on its price [...]
Biofabrication of Gingival Fibroblast Cell-Laden Collagen/Strontium-Doped Calcium Silicate 3D-Printed Bi-Layered Scaffold for Osteoporotic Periodontal Regeneration
Authors: Wang Chen-Ying , Chiu Yung-Cheng , Lee Alvin Kai-Xing , Lin Yun-An , Lin Ping-Yi , Shie Ming-You
Published: April 2021

Periodontal disease is a chronic disease that can lead to lose teeth and even tooth loss if left untreated. Osteoporosis and periodontal disease share similar characteristics and associated factors. Current regenerative techniques for periodontal diseases are ineffective in restoring complete function and structural integrity of periodontium due to unwanted migration of cells. In this study, we applied the concept of guided tissue regeneration (GTR) and 3D fabricated gingival fibroblast cell-laden collagen/strontium-doped calcium silicate (SrCS) bi-layer scaffold for periodontal regeneration. The results revealed that the bioactive SrCS had a hydroxyapatite formation on its surface after 14 days of immersion and that SrCS could release Sr and Si ions even after 6 months of immersion. In addition, in vitro results showed that the bi-layer scaffold enhanced secretion of FGF-2, BMP-2, and VEGF from human gingival fibroblasts and increased secretion of osteogenic-related proteins ALP, BSP, and OC from WJMSCs. In vivo studies using animal osteoporotic models showed that the 3D-printed cell-laden collagen/SrCS bi-layer scaffold was able to enhance osteoporotic bone regeneration, as seen from the increased Tb.Th and BV/TV ratio and the histological stains. In conclusion, it can be seen that the bi-layer scaffolds enhanced osteogenesis and further showed that guided periodontal regeneration could be achieved using collagen/SrCS scaffolds, thus making it a potential candidate for future clinical applications.
Functional Activation of Newborn Neurons Following Alcohol-Induced Reactive Neurogenesis
Authors: Nawarawong Natalie N. , Nickell Chelsea G. , Hopkins Deann M. , Pauly James R. , Nixon Kimberly
Published: April 2021

Abstinence after alcohol dependence leads to structural and functional recovery in many regions of the brain, especially the hippocampus. Significant increases in neural stem cell (NSC) proliferation and subsequent “reactive neurogenesis” coincides with structural recovery in hippocampal dentate gyrus (DG). However, whether these reactively born neurons are integrated appropriately into neural circuits remains unknown. Therefore, adult male rats were exposed to a binge model of alcohol dependence. On day 7 of abstinence, the peak of reactive NSC proliferation, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. After six weeks, rats underwent Morris Water Maze (MWM) training then were sacrificed ninety minutes after the final training session. Using fluorescent immunohistochemistry for c-Fos (neuronal activation), BrdU, and Neuronal Nuclei (NeuN), we investigated whether neurons born during reactive neurogenesis were incorporated into a newly learned MWM neuronal ensemble. Prior alcohol exposure increased the number of BrdU+ cells and newborn neurons (BrdU+/NeuN+ cells) in the DG versus controls. However, prior ethanol exposure had no significant impact on MWM-induced c-Fos expression. Despite increased BrdU+ neurons, no difference in the number of activated newborn neurons (BrdU+/c-Fos+/NeuN+) was observed. These data suggest that neurons born during alcohol-induced reactive neurogenesis are functionally integrated into hippocampal circuitry.
A Retrospective Exploratory Analysis on Cardiovascular Risk and Cognitive Dysfunction in Multiple Sclerosis
Authors: Reia Antonio , Petruzzo Martina , Falco Fabrizia , Costabile Teresa , Conenna Matteo , Carotenuto Antonio , Petracca Maria , Servillo Giuseppe , Lanzillo Roberta , Brescia Morra Vincenzo , Moccia Marcello
Published: April 2021

Background. Cardiovascular comorbidities have been associated with cognitive decline in the general population. Objectives. To evaluate the associations between cardiovascular risk and neuropsychological performances in MS. Methods. This is a retrospective study, including 69 MS patients. For all patients, we calculated the Framingham risk score, which provides the 10-year probability of developing macrovascular disease, using age, sex, diabetes, smoking, systolic blood pressure, and cholesterol levels as input variables. Cognitive function was examined with the Brief International Cognitive Assessment for MS (BICAMS), including the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-II (CVLT-II), and the Brief Visuospatial Memory Test-Revised (BVMT-R). Results. Each point increase of the Framingham risk score corresponded to 0.21 lower CVLT-II score. Looking at Framingham risk score components, male sex and higher total cholesterol levels corresponded to lower CVLT scores (Coeff = −8.54; 95%CI = −15.51, −1.57; and Coeff = −0.11; 95%CI = −0.20, −0.02, respectively). No associations were found between cardiovascular risk and SDMT or BVMT-R. Conclusions. In our exploratory analyses, cardiovascular risk was associated with verbal learning dysfunction in MS. Lifestyle and pharmacological interventions on cardiovascular risk factors should be considered carefully in the management of MS, given the possible effects on cognitive function.
Assessing the Three Attentional Networks and Vigilance in the Adolescence Stages
Authors: Giovannoli Jasmine , Martella Diana , Casagrande Maria
Published: April 2021

Attention involves three functionally and neuroanatomically distinct neural networks: alerting, orienting, and executive control. This study aimed to assess the attentional networks and vigilance in adolescents aged between 10 and 19 years using the attentional network test for interaction and vigilance (ANTI-V). One hundred and eighty-two adolescents divided into three groups (early adolescents, middle adolescents, late adolescents) participated in the study. The results indicate that after age 15, adolescents adopt a more conservative response strategy and increase the monitoring of self-errors. All the attentional networks seem to continue to develop during the age range considered in this study (10–19 y). Performance improved from early adolescence to middle adolescence and began to stabilize in late adolescence. Moreover, a low level of vigilance seems to harm alerting and orienting abilities.
Enhanced White Matter Fiber Tracts in Advanced Jazz Improvisers
Authors: Dhakal Kiran , Norgaard Martin , Dhamala Mukesh
Published: April 2021

Human cognition and behavior arise from neuronal interactions over brain structural networks. These neuronal interactions cause changes in structural networks over time. How a creative activity such as musical improvisation performance changes the brain structure is largely unknown. In this diffusion magnetic resonance imaging study, we examined the brain’s white matter fiber properties in previously identified functional networks and compared the findings between advanced jazz improvisers and non-musicians. We found that, for advanced improvisers compared with non-musicians, the normalized quantitative anisotropy (NQA) is elevated in the lateral prefrontal areas and supplementary motor area, and the underlying white matter fiber tracts connecting these areas. This enhancement of the diffusion anisotropy along the fiber pathway connecting the lateral prefrontal and supplementary motor is consistent with the functional networks during musical improvisation tasks performed by expert jazz improvisers. These findings together suggest that experts’ creative skill is associated with the task-relevant, long-timescale brain structural network changes, in support of related cognitive underpinnings.
Adjust Neuronal Reactions to Pulses of High-Frequency Stimulation with Designed Inter-Pulse-Intervals in Rat Hippocampus In Vivo
Authors: Zheng Lvpiao , Feng Zhouyan , Hu Yifan , Wang Zhaoxiang , Yuan Yue , Yang Gangsheng , Lu Chuchu
Published: April 2021

Sequences of electrical pulses have been applied in the brain to treat certain disorders. In recent years, altering inter-pulse-interval (IPI) regularly or irregularly in real time has emerged as a promising way to modulate the stimulation effects. However, algorithms to design IPI sequences are lacking. This study proposed a novel strategy to design pulse sequences with varying IPI based on immediate neuronal reactions. Firstly, to establish the correlationship between the neuronal reactions with varying IPIs, high-frequency stimulations with varying IPI in the range of 5–10 ms were applied at the alveus of the hippocampal CA1 region of anesthetized rats in vivo. Antidromically-evoked population spikes (APS) following each IPI were recorded and used as a biomarker to evaluate neuronal reactions to each pulse. A linear mapping model was established to estimate the varied APS amplitudes by the two preceding IPIs. Secondly, the mapping model was used to derive an algorithm for designing an IPI sequence that would be applied for generating a desired neuronal reaction pre-defined by a particular APS distribution. Finally, examples of stimulations with different IPI sequences designed by the algorithm were verified by rat experiments. The results showed that the designed IPI sequences were able to reproduce the desired APS responses of different distributions in the hippocampal stimulations. The novel algorithm of IPI design provides a potential way to obtain various stimulation effects for brain stimulation therapies.
Structural Changes on MRI Demonstrate Specific Cerebellar Involvement in SLE Patients—A VBM Study
Authors: Mårtensson Johan , Rumetshofer Theodor , Nystedt Jessika , Lätt Jimmy , Nilsson Petra , Bengtsson Anders , Jönsen Andreas , Sundgren Pia C.
Published: April 2021

The purpose of this study is to investigate possible differences in brain structure, as measured by T1-weighted MRI, between patients with systemic lupus erythematosus (SLE) and healthy controls (HC), and whether any observed differences were in turn more severe in SLE patients with neuropsychiatric manifestations (NPSLE) than those without (non-NPSLE). Structural T1-weighted MRI was performed on 69 female SLE patients (mean age = 35.8 years, range = 18–51 years) and 24 age-matched female HC (mean age = 36.8 years, range = 23–52 years) in conjunction with neuropsychological assessment using the CNS Vital Signs test battery. T1-weighted images were preprocessed and analyzed by FSL-VBM. The results show that SLE patients had lower grey matter probability values than the control group in the VIIIa of the cerebellum bilaterally, a region that has previously been implied in sensorimotor processing in human and non-human primates. No structural differences for this region were found between NPSLE and non-NPSLE patients. VBM values from the VIIIa region showed a weak positive correlation with the psychomotor speed domain from CNS Vital Signs (p = 0.05, r = 0.21), which is in line with its presumed role as a sensorimotor processing area.
How Much of Me Do I See in Other Minds? Modulating Egocentricity in Emotion Judgments by tDCS
Authors: Weigand Anne , Trilla Irene , Enk Lioba , O’Connell Garret , Prehn Kristin , Brick Timothy R. , Dziobek Isabel
Published: April 2021

When inferring the mental states of others, individuals’ judgments are influenced by their own state of mind, an effect often referred to as egocentricity. Self–other differentiation is key for an accurate interpretation of other’s mental states, especially when these differ from one’s own states. It has been suggested that the right supramarginal gyrus (rSMG) is causally involved in overcoming egocentricity in the affective domain. In a double-blind randomized study, 47 healthy adults received anodal (1 mA, 20 min) or sham transcranial direct current stimulation (tDCS) to the rSMG prior to performing a newly developed paradigm, the self–other facial emotion judgment (SOFE) task. In this task, participants made judgments of facial emotional expressions while having been previously confronted with congruent or incongruent emotion-inducing situations. To differentiate between emotional and cognitive egocentricity, participants additionally completed an established visual perspective-taking task. Our results confirmed the occurrence of emotional egocentric biases during the SOFE task. No conclusive evidence of a general role of the rSMG in emotional egocentricity was found. However, active as compared to sham tDCS induced descriptively lower egocentric biases when judging incongruent fearful faces, and stronger biases when judging incongruent happy faces, suggesting emotion-specific tDCS effects on egocentric biases. Further, we found significant tDCS effects on cognitive egocentricity. Results of the present study expanded our understanding of emotional egocentricity and point towards emotion-specific patterns of the underlying functionality.
Cancer: New Needs, New Models. Is It Time for a Community Oncologist? Another Brick in the Wall
Authors: Tralongo Paolo , Gebbia Vittorio , Mercadante Sebastiano , Bordonaro Roberto , Ferraù Francesco , Barni Sandro , Firenze Alberto
Published: April 2021

Over the last few decades, thanks to early detection, effective drugs, and personalized treatments, the natural history of cancer has radically changed. Thanks to these advances, we have observed how survival of cancer patients has increased, becoming an ever more important goal in cancer care. Effective clinical governance of survivorship care is essential to ensure a successful transition between active and post-treatment life, identifying optimization of healthcare outcomes and quality of life for patients as the primary objectives. For these reasons, potential intervention models must consider these differences to rationalize the available resources, including economic aspects. In this perspective, analyzing the different models proposed in the literature to manage this type of patients, we focus on the possible role of the so-called “community oncologist”. As a trained health professional, also focused on longevity, he could represent the right management solution in all those “intermediate” clinical conditions that arise between the hospital specialist, frequently overworked, and the general practitioner, often biased by the lack of specific expertise.
Palmitoylethanolamide Reduces Colon Cancer Cell Proliferation and Migration, Influences Tumor Cell Cycle and Exerts In Vivo Chemopreventive Effects
Authors: Pagano Ester , Venneri Tommaso , Lucariello Giuseppe , Cicia Donatella , Brancaleone Vincenzo , Nanì M. Francesca , Cacciola Nunzio A. , Capasso Raffaele , Izzo Angelo A. , Borrelli Francesca , Romano Barbara
Published: April 2021

Palmitoylethanolamide (PEA) is an endogenous fatty acid amide related to the endocannabinoid anandamide. PEA exerts intestinal anti-inflammatory effects, but knowledge of its role in colon carcinogenesis is still largely fragmentary. We deepened this aspect by studying the effects of PEA (ultramicronized PEA, um-PEA) on colon cancer cell proliferation, migration and cell cycle as well as its effects in a murine model of colon cancer. Results showed that um-PEA inhibited tumor cell proliferation via peroxisome proliferator-activated receptor α and G protein-coupled receptor 55, induced cell cycle arrest in the G2/M phase, possibly through cyclin B1/CDK1 upregulation, and induced DNA fragmentation. Furthermore, um-PEA reduced tumor cell migration by reducing MMP2 and TIMP1 expression. In vivo administration of um-PEA exerted beneficial effects in the azoxymethane model of colonic tumors, by reducing the number of preneoplastic lesions and tumors. Collectively, our findings provide novel proofs on the effects of um-PEA in colon carcinogenesis.
Current Perspectives on the Use of off the Shelf CAR-T/NK Cells for the Treatment of Cancer
Authors: Cutmore Lauren C. , Marshall John F.
Published: April 2021

CAR T cells have revolutionised the treatment of haematological malignancies. Despite this, several obstacles still prohibit their widespread use and efficacy. One of these barriers is the use of autologous T cells as the carrier of the CAR. The individual production of CAR T cells results in large variation in the product, greater wait times for treatment and higher costs. To overcome this several novel approaches have emerged that utilise allogeneic cells, so called “off the shelf” CAR T cells. In this Review, we describe the different approaches that have been used to produce allogeneic CAR T to date, as well as their current pre-clinical and clinical progress.
Prognostic Assessment in High-Grade Soft-Tissue Sarcoma Patients: A Comparison of Semantic Image Analysis and Radiomics
Authors: Peeken Jan C. , Neumann Jan , Asadpour Rebecca , Leonhardt Yannik , Moreira Joao R. , Hippe Daniel S. , Klymenko Olena , Foreman Sarah C. , von Schacky Claudio E. , Spraker Matthew B. , Schaub Stephanie K. , Dapper Hendrik , Knebel Carolin , Mayr Nina A. , Woodruff Henry C. , Lambin Philippe , Nyflot Matthew J. , Gersing Alexandra S. , Combs Stephanie E.
Published: April 2021

Background: In patients with soft-tissue sarcomas of the extremities, the treatment decision is currently regularly based on tumor grading and size. The imaging-based analysis may pose an alternative way to stratify patients’ risk. In this work, we compared the value of MRI-based radiomics with expert-derived semantic imaging features for the prediction of overall survival (OS). Methods: Fat-saturated T2-weighted sequences (T2FS) and contrast-enhanced T1-weighted fat-saturated (T1FSGd) sequences were collected from two independent retrospective cohorts (training: 108 patients; testing: 71 patients). After preprocessing, 105 radiomic features were extracted. Semantic imaging features were determined by three independent radiologists. Three machine learning techniques (elastic net regression (ENR), least absolute shrinkage and selection operator, and random survival forest) were compared to predict OS. Results: ENR models achieved the best predictive performance. Histologies and clinical staging differed significantly between both cohorts. The semantic prognostic model achieved a predictive performance with a C-index of 0.58 within the test set. This was worse compared to a clinical staging system (C-index: 0.61) and the radiomic models (C-indices: T1FSGd: 0.64, T2FS: 0.63). Both radiomic models achieved significant patient stratification. Conclusions: T2FS and T1FSGd-based radiomic models outperformed semantic imaging features for prognostic assessment.
NTRK Fusion Genes in Thyroid Carcinomas: Clinicopathological Characteristics and Their Impacts on Prognosis
Authors: Pekova Barbora , Sykorova Vlasta , Mastnikova Karolina , Vaclavikova Eliska , Moravcova Jitka , Vlcek Petr , Lastuvka Petr , Taudy Milos , Katra Rami , Bavor Petr , Kodetova Daniela , Chovanec Martin , Drozenova Jana , Astl Jaromir , Hrabal Petr , Vcelak Josef , Bendlova Bela
Published: April 2021

Chromosomal rearrangements of NTRK genes are oncogenic driver mutations in thyroid cancer (TC). This study aimed to identify NTRK fusion-positive thyroid tumors and to correlate them with clinical and pathological data and determine their prognostic significance. The cohort consisted of 989 different TC samples. Based on the detected mutation, samples were triaged, and those that were positive for a BRAF, HRAS, KRAS, NRAS, RET, RET/PTC or PAX8/PPARγ mutation were excluded from further analyses. NTRK fusion gene testing was performed in 259 cases, including 126 cases using next-generation sequencing. NTRK fusion genes were detected in 57 of 846 (6.7%) papillary thyroid carcinomas and in 2 of 10 (20.0%) poorly differentiated thyroid carcinomas. A total of eight types of NTRK fusions were found, including ETV6/NTRK3, EML4/NTRK3, RBPMS/NTRK3, SQSTM1/NTRK3, TPM3/NTRK1, IRF2BP2/NTRK1, SQSTM1/NTRK1 and TPR/NTRK1.NTRK fusion-positive carcinomas were associated with the follicular growth pattern, chronic lymphocytic thyroiditis and lymph node metastases. NTRK1-rearranged carcinomas showed a higher frequency of multifocality and aggressivity than NTRK3-rearranged carcinomas. Tumor size, presence of metastases, positivity for the NTRK3 or NTRK1 fusion gene and a late mutation event (TERT or TP53 mutation) were determined as factors affecting patient prognosis. NTRK fusion genes are valuable diagnostic and prognostic markers.