bluuebunny/crossref_metadata_2025 huggingface dataset:
What Are the Health Benefits of Organized Sports?
Authors: Claus Connor , Miller Jami , Miller Tamara B.
Published: October 2022

Joining an organized sport through school, your community, or a club is a great way to stay physically active. Staying active is an important part of staying healthy. This article will talk about how participating in organized sports can increase your physical activity level, keep your heart strong so you can run without getting as tired, strengthen your bones to avoid bone weakening, and keep your thoughts positive so you do not give up when activities get difficult. This article will discuss which sports bring about which benefits, how long these benefits last, and how long you have to play a sport to see progress. Because some of the health improvements have their maximum effect when they are started during adolescence, you should probably start reading about the benefits and then start moving!
Evaluating the influencing factors of food imports within belt and road initiatives (BRI) countries: An economic threshold model approach
Authors: Wang Yameng , Sarkar Apurbo
Published: October 2022

International food chains and trade usually support many vulnerable and food-insecure developing countries to ensure stable access to food and sufficient resources to maintain and enhance economic growth. However, the smooth transition of uninterrupted food trade and supply is one of the major concerns for almost every country. Based on the economic threshold model grouping tactics, the study evaluates the influencing factors of global food imports and how different countries foster food imports in different conditions. The empirical data has been comprised of panel data from 91 countries along the “Belt and Road” for the last 21 years. The results show that: (i) Population size and arable land endowment have single and double threshold effects on food imports. (ii) Economic development has different effects on the food imports of each group of countries. It has an inverted U-shaped relationship with countries with large populations and high arable land endowments and a “U-shaped relationship” with countries with low arable land endowments. There is a linear relationship between the food imports of countries with small populations and medium arable land endowments, and there is no significant impact on food imports of countries with large populations and medium arable land endowments. (iii) The impact of infrastructure, technological progress, food stocks, and industrial structure on food imports varies from country to country, but tariff policies have no significant impact on food imports. All member countries should utilize the platform of “Belt and Road Initiatives” to capture the resource endowment and exchange associated science and technology of food production, processing, transport, and storage. Food productivity and self-dependency on food should also be increased.
Orthopedic therapeutic surgery for bone metastasis of liver cancer: Clinical efficacy and prognostic factors
Authors: Lian Qiujian , Liu Chang , Chen Fengmei , Wang Bingxuan , Wang Miao , Qiao Suchi , Guan Zhengmao , Jiang Shuai , Wang Zhiwei
Published: October 2022

Objectives

In this study, the objectives were to investigate the clinical efficacy of orthopedic therapeutic surgery (OTS) in patients with bone metastasis of liver cancer and explore the prognostic factors.

Methods

The electronic medical records of patients with bone metastasis of liver cancer in the Third Affiliated Hospital of Naval Medical University from September 2016 to August 2021 were retrospectively collected. A total of 53 patients were included. Patients were assigned to the OTS (n = 35) or the control group (n = 18) based on receiving orthopedic therapeutic surgery or conservative treatment. The pre/posttreatment Karnofsky Performance Status scale (KPS) and numeric rating scale (NRS) scores were compared. Univariate and multivariate Cox regression analyses were used to explore the prognostic factors affecting survival after bone metastasis. Logistic regression analyses were adopted to discover potential factors that contributed to greater KPS score improvement.

Results

The axial bone accounted for 69.8% of all bone metastases. The proportion of multiple bone metastases was 52.8%. After surgery, the median KPS score of the OTS group increased from 60 to 80 (p < 0.001), and the median increase in the OTS group was higher than that of the control group (p = 0.033). The median NRS score of the OTS group declined from 6 to 2 after surgery (p < 0.001), and the median decline in the OTS group was higher (p = 0.001). The median survival was 10 months in the OTS group vs. 6 months in the control group (p < 0.001). Higher pretreatment KPS scores, undergoing liver primary lesion surgery, and undergoing orthopedic therapeutic surgery were protective factors of survival. Undergoing orthopedic therapeutic surgery greatly improved the KPS score.

Conclusions

Orthopedic therapeutic surgery for bone metastasis of liver cancer provides benefits to the quality of life. Patients who have their primary liver lesions removed, undergo orthopedic therapeutic surgery, and have a better physical condition before treatment tend to have longer survival.
Numerical assessment of thermal management on the capacity fade of lithium-ion batteries in electric vehicles
Authors: Carnovale Andrew , Li Xianguo
Published: October 2022

Electric vehicles, as a major strategy for climate change mitigation, uses lithium-ion batteries extensively as the power source. However, the operation, performance and lifetime of lithium-ion batteries depend on the battery temperature, which can have a wide range due to heat generation within the battery and significant variations in the ambient conditions due to changes in seasons and geographical locations where electric vehicles are operated. In the present study, thermal management methods/strategies on the capacity fade of lithium-ion batteries are assessed through a validated capacity fade model for lithium-ion batteries along with a thermal model for the heat generation in the battery and dissipation over battery surface, represented by various thermal management methods. The driving conditions are simulated through a constant and various standard drive cycles. It is shown that battery temperature has the predominant impact on the capacity fade, and it can be controlled through effective thermal management. A much more significant spread in battery capacity fade occurs with various thermal management methods for a lower initial battery temperature (20°C) compared to the higher temperatures (35°C and 50°C), hence, thermal management is much more effective in reducing capacity fade at battery temperatures close to 20°C, which is considered the optimum operating temperature for lithium-ion batteries. Further, the results indicate that using a lower charge voltage can result in slightly less capacity fade over cycling. Regenerative braking makes it more realistic to use lower charge voltages, since the battery can be recharged during operation, thereby increasing driving range, while preventing increased capacity fade. Effective thermal management is more imperative for realistic intense and aggressive driving behaviors.
Patterns and risk factors of avian influenza A(H5) and A(H9) virus infection in pigeons and quail at live bird markets in Bangladesh, 2017–2021
Authors: Islam Ariful , Islam Shariful , Amin Emama , Hasan Rashedul , Hassan Mohammad Mahmudul , Miah Mojnu , Samad Mohammed Abdus , Shirin Tahmina , Hossain Mohammad Enayet , Rahman Mohammed Ziaur
Published: October 2022

The avian influenza virus (AIV) impacts poultry production, food security, livelihoods, and the risk of transmission to humans. Poultry, like pigeons and quail farming, is a growing sector in Bangladesh. However, the role of pigeons and quails in AIV transmission is not fully understood. Hence, we conducted this study to investigate the prevalence and risk factors of AIV subtypes in pigeons and quails at live bird markets (LBMs) in Bangladesh. We collected oropharyngeal and cloacal swab samples from 626 birds in 8 districts of Bangladesh from 2017 to 2021. We tested the swab samples for the matrix gene (M gene) followed by H5, H7, and H9 subtypes using real-time reverse transcriptase-polymerase chain reaction (rRT-PCR). We then used exploratory analysis to investigate the seasonal and temporal patterns of AIV and a mixed effect logistic model to identify the variable that influences the presence of AIV in pigeons and quails. The overall prevalence of AIV was 25.56%. We found that the prevalence of AIV in pigeons is 17.36%, and in quail is 38.75%. The prevalence of A/H5, A/H9, and A/H5/H9 in quail is 4.17, 17.92, and 1.67%, respectively. Furthermore, the prevalence of A/H5, A/H9, and A/H5/H9 in pigeons is 2.85, 2.59, and 0.26%. We also found that the prevalence of AIV was higher in the dry season than in the wet season in both pigeons and quail. In pigeons, the prevalence of A/untyped (40%) increased considerably in 2020. In quail, however, the prevalence of A/H9 (56%) significantly increased in 2020. The mixed-effect logistic regression model showed that the vendors having waterfowl (AOR: 2.13; 95% CI: 1.04–4.33), purchasing birds from the wholesale market (AOR: 2.96; 95% CI: 1.48–5.92) instead of farms, mixing sick birds with the healthy ones (AOR: 1.60; 95% CI: 1.04–2.45) and mingling unsold birds with new birds (AOR: 3.07; 95% CI: 2.01–4.70) were significantly more likely to be positive for AIV compared with vendors that did not have these characteristics. We also found that the odds of AIV were more than twice as high in quail (AOR: 2.57; 95% CI: 1.61–4.11) as in pigeons. Furthermore, the likelihood of AIV detection was 4.19 times higher in sick and dead birds (95% CI: 2.38–7.35) than in healthy birds. Our study revealed that proper hygienic practices at the vendors in LBM are not maintained. We recommend improving biosecurity practices at the vendor level in LBM to limit the risk of AIV infection in pigeons and quail in Bangladesh.
Maternal nucleotide supplementation improves the intestinal morphology and immune function in lipopolysaccharide-challenged newborn piglets
Authors: Li Qiming , Hung Ifen , Bai Kaiwen , Wang Tian
Published: October 2022

This study aimed to evaluate the effects of maternal nucleotide (NT) supplementation on intestinal morphology and immune function in lipopolysaccharide-challenged newborn piglets. At 85 d gestation, 12 sows were selected and assigned to two groups: the CON group (basal diet, n = 6) and the NT group (basal diet with 1 g/kg NT mixture, n = 6). After parturition, newborn piglets were collected without suckling. Piglets from the CON group were intraperitoneally injected with sterile saline or lipopolysaccharide (LPS, 10 mg/kg body weight), and divided into the C-CON (n = 6) and C-LPS groups (n = 6). Piglets from the NT group received the same treatment and were divided into the N-CON (n = 6) and N-LPS groups (n = 6). The blood and small intestinal samples of piglets were collected 1 h after injection. The results showed that: (1) maternal NT supplementation increased the concentrations of serum complement C3 and C4 (P < 0.05), and suppressed the increase in serum hypersensitive C-reactive protein in LPS-challenged newborn piglets (P < 0.05); (2) maternal NT supplementation increased the villus height and the ratio of villus height to crypt depth in the duodenum of newborn piglets (P < 0.05) and inhibited the LPS-induced decrease in the villus height in the jejunum and ileum (P < 0.05). (3) The LPS-induced increased levels of interleukin-6 in the jejunum and tumor necrosis factor-α in the ileum of newborn piglets were suppressed by maternal NT supplementation (P < 0.05). (4) In the jejunum of newborn piglets, maternal NT supplementation inhibited the LPS-induced increase in toll-like receptor 4 (TLR4) mRNA and protein expression (P < 0.05) and the decrease of nuclear factor-κB inhibitor α (IκBα) protein expression (P < 0.05). In the ileum, piglets had a lower nuclear factor-κB (NFκB) mRNA expression in the NT groups than the CON groups (P < 0.05), and maternal NT supplementation suppressed the decrease of IκBα mRNA in LPS-treated piglets (P < 0.05). In conclusion, maternal NT supplementation could promote the intestinal development and immune function of newborn piglets, and may improve LPS-induced intestinal inflammatory responses via the TLR4/IκBα/NFκB pathway.
Ultrasound-guided injection technique of the equine cervical nerve roots
Authors: Fouquet Gregoire , Abbas Ghazanfar , Johnson Jessica P. , Pompermayer Endrigo , Harel Camille , Aldous Eman , Puchalski Sarah , David Florent
Published: October 2022

Radiculopathy in horses is often a diagnosis of exclusion because of the non-specific clinical signs related to neck pain and possible forelimb lameness. There are no reported treatment options in the equine veterinary literature. The purpose of the study was to describe an ultrasound-guided injection of the cervical nerve root C3 to C8, to evaluate accuracy, time and safety and to anticipate possible complications on clinical cases. Under general anesthesia and with ultrasound guidance, five horses were injected from C3 to C8 with 1.5mL mix of contrast and latex. Immediately after euthanasia, the necks were taken for CT examination and then dissection was performed 3 days later. Data regarding the accuracy of injection, the presence of injectate in the nerve root, vertebral vessel or vertebral canal were recorded from both CT and dissection. The time of injection and ability to visualize the nerve root prior to injection were also recorded. Out of 60 intended injections, 55 (CT images) and 57 (dissection) led to injectate deposited within the target zone with direct contact between contrast/latex and cervical nerve roots noted in 76.4% and 73.7%, respectively. Presence of contrast/latex injectate within nerves (≤11%), vertebral vessels (<4%) and canal (<4%) were rarely encountered. No variation on success rate or safety noted based on the site of injection. The technique described has excellent accuracy, with injectate deposition in direct contact (≈75%) or close vicinity (≈25%) of C3-C8 cervical nerve roots. Injectate diffusion is likely to further improve success rate. Rare presence of injectate within nerve/sheath, vertebral vessels/canal along with diffusion warrants caution when performing this procedure in clinical cases.
UTM Architecture and Flight Demonstration in Korea
Authors: Jung Kyusur , Kim Songju , Jung Beechuilla , Kim Seyeon , Kang Hyunwoo , Kang Changbong
Published: October 2022

Unmanned Aircraft System Traffic Management (UTM) is a traffic management system enabling drones to safely and efficiently fly in low-altitude airspace below 120~150m (400~500ft). UTM provides services such as communication, flight route management, location monitoring, and collision avoidance so that drones completing various missions can fly beyond visual line of sight (BVLOS) safely and increase the usability of airspace. In other words, UTM is a new air traffic management for drones with high levels of automation, advanced decision making and control. Many countries around the world are developing UTM systems that systematically manage the traffic of drones flying at low altitude. In Korea, UTM research has been ongoing as an R&D project since 2017. The purpose of this paper is to introduce the Korean UTM system and to apply it to actual flight demonstration through the developed operational procedures. The approach of this article is to establish Korean UTM architecture through existing references and examples from other countries, devise an operational procedure suitable for the system, and describe the results of using it for flight demonstration. In other words, this paper covers Korea’s UTM architecture, operational procedures, and flight demonstration through a macro approach to UTM. In addition, this paper presents policy and technical challenges that UTM must go through and that need to be solved in the future, which are classified into four categories.
Preliminary Research on the Effects of Different Substrates on the Metabolome of Potted Peonies
Authors: Zhu Yujie , Chen Xia , Hu Yiyou , Zhao Huayuan , Wang Huasen , Li Hongli , Zheng Zijie , Zhu Xiangtao
Published: October 2022

Peony (Paeonia suffruticosa Andr.) is a traditional ornamental flower in China. Peony potted culture has become mainstream. The development of agricultural and forestry waste instead of a nonrenewable peat matrix as the substrate is an important direction for the future industry of potted peonies. However, the mechanism of the effects of different substrates on the growth and development of peonies remains unclear. In this experiment, “Luhehong”, a peony variety from Heze, Shandong Province, was selected as the main experimental material. The response mechanism of peony roots to different substrate proportions was analyzed using untargeted metabolomics of potted peonies. Results showed that the potential for pot growth of planted peonies using the mixed-straw mixing matrix (Matrix K) is better than that of the rice husk matrix (Matrix G) and the control matrix. Moreover, the comparative analysis of the metabolic groups indicates that the number of peony root secretions in the three matrices has a remarkable difference, possibly related to the nutrition supply levels of the peony roots, in the different matrices of adaptive response and adjustment. Furthermore, (2r)-3-hydroxyisovaleroylcarnitine, trigonelline, 2-acetylresorcinol, and dehydroascorbic acid (oxidized vitamin C)—four metabolites with the most substantial intergroup differences—are considered key metabolites. The metabolic pathway analysis of propanoate, and ascorbate and aldarate metabolism, and the two pathways related to an environmental response, namely, ABC transporters and phosphatidylinositol signaling system, indicated that these pathways were remarkably enriched. Both may be the key way to affect the growth and development of potted peonies. This study can provide an important reference for the rational allocation of the substrate of agricultural and forestry waste in potted peony cultivation and application.
Animal Welfare Compromises Associated with Causes of Death in Neonatal Piglets
Authors: Chidgey Kirsty L. , Udomteerasuwat Nutnapong , Morel Patrick C. H. , Castillo-Alcala Fernanda
Published: October 2022

This pilot study aimed to assess the welfare impacts of different causes of pre-weaning deaths in piglets. Piglets that died between 0–7 days after birth (n = 106) were collected from two commercial pig farms and subject to post-mortem examination to confirm their cause of death as well as any contributing factors. Using the Five Domains Model, the most likely affective experiences associated with the pathological findings were carefully inferred to better understand affective experience as it related to known causes of liveborn piglet mortality. The most common causes of liveborn piglet mortality were starvation (23%), crushing (23%) and non-viable (21%). Thirty one piglets had evidence of starvation, but it was only considered the primary cause of death in 15 piglets, as cofactors such as poor viability (n = 13) were also present in many piglets with evidence of starvation. All 15 piglets that were crushed died within 24 h after birth and most had evidence of thoracic and/or abdominal internal bleeding. This study found that common causes of liveborn piglet death were associated with compromises in Domains 1 (Nutrition/hydration), 3 (Health/function), and4 (Behavioural interactions), with the most likely resulting affective states described in Domain 5 (Mental state). This highlights the interaction between physical/functional and situation-related (behavioural) aspects that influence an animals’ welfare status.
Nontraumatic Paraureteral Urinoma in a Cat with Urolithiasis
Authors: Tabbì Marco , Rifici Claudia , Cicero Luca , Macrì Francesco , Mazzullo Giuseppe , Sfacteria Alessandra , Cassata Giovanni , De Majo Massimo , Di Pietro Simona
Published: October 2022

Urinoma is an encapsulated collection of urine due to a disruption in the collection system of the urinary tract. This condition is rarely reported in veterinary medicine. The aim of this study is to describe the clinical and diagnostic findings of a well-encapsulated paraureteral urinoma associated with urinary tract stones in a critical feline patient. The ultrasound examination of the abdomen revealed a well-defined collection of anechoic fluid containing the left kidney in the retroperitoneal space, while the radiographic examination revealed a loss of soft tissue contrast in the lumbar region. Both techniques confirmed the presence of stones in the bladder. Following the ultrasound-guided drainage of the lesion, the nature of the fluid was also confirmed to be urine. Due to the worsening of the cat’s health, to better define the extent and genesis of the lesion, a positive contrast radiographic study was performed by means of an ultrasound-guided percutaneous injection of a contrast medium into the lesion, which highlighted a wide and homogeneous radiopaque area in the left retroperitoneal space. These findings were confirmed with a postmortem examination, corroborating the diagnostic suspicion of urinoma. The percutaneous contrast inoculation performed in this critically ill patient plays a role in the diagnostic process to reach a final diagnosis in cases in which the patient’s clinical condition does not allow for performing an excretory positive contrast study.
Advanced Techniques for the Intelligent Diagnosis of Fish Diseases: A Review
Authors: Li Daoliang , Li Xin , Wang Qi , Hao Yinfeng
Published: October 2022

Aquatic products, as essential sources of protein, have attracted considerable concern by producers and consumers. Precise fish disease prevention and treatment may provide not only healthy fish protein but also ecological and economic benefits. However, unlike intelligent two-dimensional diagnoses of plants and crops, one of the most serious challenges confronted in intelligent aquaculture diagnosis is its three-dimensional space. Expert systems have been applied to diagnose fish diseases in recent decades, allowing for restricted diagnosis of certain aquaculture. However, this method needs aquaculture professionals and specialists. In addition, diagnosis speed and efficiency are limited. Therefore, developing a new quick, automatic, and real-time diagnosis approach is very critical. The integration of image-processing and computer vision technology intelligently allows the diagnosis of fish diseases. This study comprehensively reviews image-processing technology and image-based fish disease detection methods, and analyzes the benefits and drawbacks of each diagnostic approach in different environments. Although it is widely acknowledged that there are many approaches for disease diagnosis and pathogen identification, some improvements in detection accuracy and speed are still needed. Constructing AR 3D images of fish diseases, standard and shared datasets, deep learning, and data fusion techniques will be helpful in improving the accuracy and speed of fish disease diagnosis.
Similarity-Based Malware Classification Using Graph Neural Networks
Authors: Chen Yu-Hung , Chen Jiann-Liang , Deng Ren-Feng
Published: October 2022

This work proposes a novel malware identification model that is based on a graph neural network (GNN). The function call relationship and function assembly content obtained by analyzing the malware are used to generate a graph that represents the functional structure of a malware sample. In addition to establishing a multi-classification model for predicting malware family, this work implements a similarity model that is based on Siamese networks, measuring the distance between two samples in the feature space to determine whether they belong to the same malware family. The distance between the samples is gradually adjusted during the training of the model to improve the performance. A Malware Bazaar dataset analysis reveals that the proposed classification model has an accuracy and area under the curve (AUC) of 0.934 and 0.997, respectively. The proposed similarity model has an accuracy and AUC of 0.92 and 0.92, respectively. Further, the proposed similarity model identifies the unseen malware family with approximately 70% accuracy. Hence, the proposed similarity model exhibits better performance and scalability than the pure classification model and previous studies.
Effects of Local Vegetation and Regional Controls in Near-Surface Air Temperature for Southeastern Brazil
Authors: de Abreu Rafael Cesario , Hallak Ricardo , da Rocha Humberto Ribeiro
Published: October 2022

The spatial range of near-surface air temperature average and trends for Southeast Brazil in recent decades motivated us to investigate the causality of local vegetation and other geophysical controls at the regional scale to explain the spatial variability of the average maximum and minimum temperature (Tmax and Tmin). We used measurements from 52 weather stations between 1985 and 2010. Using linear regression, NDVI and cloud cover were significant to explain spatial variability of Tmax and Tmin. With the Generalized Additive Model (GAM), we improved temperature-dependent relationships with regional geophysical controls, and local scale NDVI. The modeling of Tmax and Tmin showed non-linear and combined relationships with geographical position (lat,lon) jointly expressing the effects of zonality and continentality, and NDVI at distances of 300 m and 3000 m. For Tmin, geographical position and altitude responded with an amplitude of ≃5 °C each, and NDVI with ≃3 °C. Similarly, the geographical position and altitude were significant for Tmax, with an amplitude of ≃5 °C each, and cloud cover with ≃3.5 °C. Our findings help to clarify the local scale controls of near-surface air temperature and stress the need to increase resilience against adversities of global climate change and increasing urbanization, by providing metrics to predict the effects of nature-based solutions within the urban space.
An Empirical Equation for Wet-Bulb Temperature Using Air Temperature and Relative Humidity
Authors: Chen Hsuan-Yu , Chen Chia-Chung
Published: October 2022

Climate change causes extreme heat and high humidity in some regions. The wet-bulb temperature (Tw) is a heat stress index, and the threshold is 35 °C. It is difficult to measure the value of Tw using a psychrometer, but the Tw value can be calculated using the air temperature and humidity. To provide accuracy for the Tw calculation, an empirical equation is established using regression analysis. This study defines the empirical equation as Tw=−4.391976+0.0198197RH+0.526359Td+0.00730271RH·Td+2.4315×10−4RH2−2.58101×10−5Td·RH2, where Td is the air temperature in °C and RH is the relative humidity in %. This equation applies to a temperature of 20~45 °C and RH of 40~99%. The fit is better than that for the Stull equation in this range. The prediction accuracy is 0.022 °C and there is no fixed pattern for the error distribution for the range of Td and RH. The measurement uncertainty for Tw values for thermometer and humidity sensors that are not calibrated is 1.4~2.2%. If these sensors are calibrated, the measurement uncertainty for Tw values is 0.16~0.28 °C. Therefore, well-calibrated sensors are necessary to enhance the accuracy of the Tw predictive equation.
Negative Pressure Wound Therapy in Spinal Surgery
Authors: White Alexandra Jeanne , Gilad Ronit , Motivala Soriaya , Fiani Brian , Rasouli Jonathan
Published: October 2022

Negative pressure wound therapy (NPWT) has demonstrated promise in the management of surgical site infections as well as assisting in surgical wound healing. In this manuscript, we describe the mechanisms and applications of NPWT for surgical wounds and existing evidence for NPWT in cardiac, plastic, and general surgery, followed by a discussion of the emerging evidence base for NPWT in spinal surgery. We also discuss the different applications of NPWT for open wounds and closed incisions, and the promise of newer closed-incision NPWT (ciNPWT) devices. There is nominal but promising prospective evidence on NPWT’s efficacy in select at-risk populations for post-operative wound complications after spinal surgery. As there is currently a paucity of robust clinical evidence on its efficacy, rigorous randomized prospective clinical trials are needed.
TNS1: Emerging Insights into Its Domain Function, Biological Roles, and Tumors
Authors: Wang Zhihui , Ye Jingxue , Dong Fengrui , Cao Li , Wang Min , Sun Guibo
Published: October 2022

Tensins are a family of cellular-adhesion constituents that have been extensively studied. They have instrumental roles in the pathogenesis of numerous diseases. The mammalian tensin family comprises four members: tensin1 (TNS1), tensin2, tensin3, and tensin4. Among them, TNS1 has recently received attention from researchers because of its structural properties. TNS1 engages in various biological processes, such as cell adhesion, polarization, migration, invasion, proliferation, apoptosis, and mechano-transduction, by interacting with various partner proteins. Moreover, the abnormal expression of TNS1 in vivo is associated with the development of various diseases, especially tumors. Interestingly, the role of TNS1 in different tumors is still controversial. Here, we systematically summarize three aspects of TNS1: the gene structure, the biological processes underlying its action, and the dual regulatory role of TNS1 in different tumors through different mechanisms, of which we provide the first overview.
The Role of Gut Microbiota in Heart Failure: When Friends Become Enemies
Authors: Cianci Rossella , Franza Laura , Borriello Raffaele , Pagliari Danilo , Gasbarrini Antonio , Gambassi Giovanni
Published: October 2022

Heart failure is a complex health issue, with important consequences on the overall wellbeing of patients. It can occur both in acute and chronic forms and, in the latter, the immune system appears to play an important role in the pathogenesis of the disease. In particular, in the forms with preserved ejection fraction or with only mildly reduced ejection fraction, some specific associations with chronic inflammatory diseases have been observed. Another interesting aspect that is worth considering is the role of microbiota modulation, in this context: given the importance of microbiota in the modulation of immune responses, it is possible that changes in its composition may somewhat influence the progression and even the pathogenesis of heart failure. In this narrative review, we aim to examine the relationship between immunity and heart failure, with a special focus on the role of microbiota in this pathological condition.
Changes in CSF Surface Tension in Relation to Surfactant Proteins in Children with Intraventricular Hemorrhage
Authors: Reger Rieka M. , Meinicke Anton , Härtig Wolfgang , Knüpfer Matthias , Thome Ulrich , Schob Stefan , Krause Matthias
Published: October 2022

The regulation of surface tension (ST) by surfactants plays an important role in the human respiratory system but is largely unexplored in brain homeostasis. The aim of this study was to evaluate changes in ST in relation to surfactant proteins (SPs) in children with intraventricular hemorrhage (IVH). CSF samples from 93 patients were analyzed for ST with a force tensiometer and SP-A-D and -G with ELISA assays. Patients belonged to six groups: (i) IVH before primary intervention (PI), (ii) IVH 4–28 days after PI, (iii) IVH 44–357 days after PI, (iv) hydrocephalus, (v) sepsis and (vi) controls. We found indirect correlations and significant differences in ST and SPs (all p < 0.001; except for SP-C, p = 0.007). Post hoc analyses showed significantly decreased ST in IVH patients before PI compared with patients with hydrocephalus, sepsis or controls (p < 0.001), but it increased in IVH patients over time. All SPs were significantly elevated when comparing IVH patients before PI with controls (all p < 0.001; except for SP-C, p = 0.003). Children suffering from IVH displayed an increase in SPs and a decrease in ST as coping mechanisms to preserve CSF flow. The increase in ST over time could serve as prognostic marker for the healing process.
Affection of Surgical Decompressive Scale of Optic Canal to Traumatic Optic Neuropathy
Authors: Li Xinyu , Guo Zhilin
Published: October 2022

Traumatic optic neuropathy (TON) is damage to the optic nerve that is caused by external violence to the optic nerve during cranial and facial trauma. This kind of injury may result in impaired vision, has a high risk of blindness, and significantly impairs the neurological function of the patient. The treatment of TON is controversial, and many different approaches have been suggested. No one is considered best because the traumatic mechanism is not clear. Methods: In this retrospective study, the clinical features of 37 patients diagnosed with TON without light perception who were treated at the Ninth People’s Hospital of Shanghai Jiao Tong University School of Medicine were investigated. A comparison was made between the patient’s visual results before and after therapy. In addition, using a multifactorial linear regression model, the independent risk variables for the degree of improvement in visual acuity (IDVA) following surgery were determined. Results: After the operation, 17 people’s visual acuity (VA) was lightless, 20 people’s visual acuity was improved, and 13 people’s visual acuity reached the standard of decerebrate. The efficiency of total optic nerve decompression was 54.1%, and the unblinded rate was 35.1%. Multiple linear regression analysis revealed that fractures of the optic canal and orbit were independent predictors of postoperative VA and IDVA. Conclusions: Total optic canal decompression may efficiently and safely enhance the vision of patients who have TON. Patients with TON who do not have fractures of the optic canal and orbit prior to decompression had a more favorable surgical prognosis.
Analysis of Risk Factors for Cerebral Microbleeds and the Relationship between Cerebral Microbleeds and Cognitive Impairment
Authors: Zheng Huiwen , Yuan Yong , Zhang Zuohui , Zhang Jing
Published: October 2022

(1) Background: Cerebral microbleeds (CMBs) are attracting increasing attention. Nevertheless, the risk factors for CMBs remain poorly identified, and the relationship between CMBs and cognitive impairment is still up for debate; (2) Objective: The present study analyzed the risk factors for CMBs and probed into the potential correlations between the presence, number, and location of CMBs and cognition; (3) Methods: This study enrolled 406 subjects who underwent both brain 3.0-T magnetic resonance imaging scans and cognitive testing. Spearman correlation was used to assess the relationship between the number of CMBs and cognition. Multiple linear regression was utilized to analyze the relationship between the regions of CMBs and each cognitive domain; (4) Results: Multivariate logistic regression analysis results showed that age (odds ratio (OR) = 1.045, 95% confidence interval (95%CI; 1.009, 1.082)), smoking (OR = 3.604, 95%CI (1.995, 6.509)), hypertension (OR = 3.607, 95%CI (2.204, 5.901)), total cholesterol (OR = 0.611, 95%CI (0.467, 0.799)), and Amyloid-β1-42 (Aβ1-42) (OR = 1.028, 95%CI (1.018, 1.037)) were the influencing factors of CMBs. Education years (OR = 0.959, 95%CI (0.930, 0.988)), white matter lesions (OR = 2.687, 95%CI (1.782, 4.051)), and CMBs (OR = 21.246, 95%CI (5.728, 21.576)) were the risk factors for cognitive impairment. Hypertension increased the probability of deep CMBs (OR = 12.54, 95%CI (2.21, 71.28)), while Aβ1-42 elevated the probability of lobar CMBs (OR = 1.02, 95%CI (1.00, 1.03)). There was a linear correlation between the number of CMBs and Montreal Cognitive Assessment scores (r = −0.756, p < 0.001). However, CMBs in each region were not related to specific cognitive domains (p > 0.05), except CMBs in the mixed group that were negatively correlated with attention (OR = −0.669, 95%CI (−0.034, −5.270)); (5) Conclusions: Taken together, serum Aβ1-42 levels are related to the presence of CMBs. Cognitive impairment is correlated with the number of CMBs rather than their region. These findings suggest that CMBs play a role in cognitive impairment and that CMBs mark the presence of diffuse vascular injury and neurodegenerative brain damage.
Neural Component of the Tumor Microenvironment in Pancreatic Ductal Adenocarcinoma
Authors: Gola Michał , Sejda Aleksandra , Godlewski Janusz , Cieślak Małgorzata , Starzyńska Anna
Published: October 2022

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive primary malignancy of the pancreas, with a dismal prognosis and limited treatment options. It possesses a unique tumor microenvironment (TME), generating dense stroma with complex elements cross-talking with each other to promote tumor growth and progression. Diversified neural components makes for not having a full understanding of their influence on its aggressive behavior. The aim of the study was to summarize and integrate the role of nerves in the pancreatic tumor microenvironment. The role of autonomic nerve fibers on PDAC development has been recently studied, which resulted in considering the targeting of sympathetic and parasympathetic pathways as a novel treatment opportunity. Perineural invasion (PNI) is commonly found in PDAC. As the severity of the PNI correlates with a poorer prognosis, new quantification of this phenomenon, distinguishing between perineural and endoneural invasion, could feature in routine pathological examination. The concepts of cancer-related neurogenesis and axonogenesis in PDAC are understudied; so, further research in this field may be warranted. A better understanding of the interdependence between the neural component and cancer cells in the PDAC microenvironment could bring new nerve-oriented treatment options into clinical practice and improve outcomes in patients with pancreatic cancer. In this review, we aim to summarize and integrate the current state of knowledge and future challenges concerning nerve–cancer interactions in PDAC.
The Potential Role of 3D In Vitro Acute Myeloid Leukemia Culture Models in Understanding Drug Resistance in Leukemia Stem Cells
Authors: Al-Kaabneh Basil , Frisch Benjamin , Aljitawi Omar S.
Published: October 2022

The complexity of the bone marrow (BM) microenvironment makes studying hematological malignancies in vitro a challenging task. Three-dimensional cell cultures are being actively studied, particularly due to their ability to serve as a bridge of the gap between 2D cultures and animal models. The role of 3D in vitro models in studying the mechanisms of chemotherapeutic resistance and leukemia stem cells (LSCs) in acute myeloid leukemia (AML) is not well-reviewed. We present an overview of 3D cell models used for studying AML, emphasizing the recent advancements in microenvironment modeling, chemotherapy testing, and resistance.
Tyrosine Kinase Inhibitor Independent Gene Expression Signature in CML Offers New Targets for LSPC Eradication Therapy
Authors: Gómez-Castañeda Eduardo , Hopcroft Lisa , Rogers Simon , Munje Chinmay , Bittencourt-Silvestre Joana , Copland Mhairi , Vetrie David , Holyoake Tessa , Jørgensen Heather
Published: October 2022

Tyrosine kinase inhibitors (TKI) have revolutionised the treatment of CML. However, TKI do not eliminate the leukaemia stem cells (LSC), which can re-initiate the disease. Thus, finding new therapeutic targets in CML LSC is key to finding a curative treatment. Using microarray datasets, we defined a list of 227 genes that were differentially expressed in CML LSC compared to the healthy controls but were not affected by TKI in vitro. Two of them, CD33 and PPIF, are targeted by gemtuzumab–ozogamicin and cyclosporin A, respectively. We treated CML and the control CD34+ cells with either drug with or without imatinib to investigate the therapeutic potential of the TKI-independent gene expression programme. Cyclosporine A, in combination with imatinib, reduced the number of CML CFC compared with non-CML controls, but only at supra-therapeutic concentrations. Gemtuzumab–ozogamicin showed an EC50 of 146 ng/mL, below the plasma peak concentration of 630 ng/mL observed in the AML patients and below the EC50 of 3247 ng/mL observed in the non-CML cells. Interestingly, gemtuzumab–ozogamicin seems to promote cell cycle progression in CML CD34+ cells and demonstrated activation of the RUNX1 pathway in an RNAseq experiment. This suggests that targeting the TKI-independent genes in CML LSC could be exploited for the development of new therapies in CML.
A New Source of Heterogeneity in Comparative and Translational Clinical Trials: The “Border-Time” Bias
Authors: Santorsola Mariachiara , Caraglia Michele , Nasti Guglielmo , Ottaiano Alessandro
Published: October 2022

The use of target-oriented drugs is profoundly changing the anti-cancer treatments. This new and expanding therapeutic context relies on the translation of biomarkers expression (laboratory testing) into clinical practice (treatment). Progression-free survival is a primary or co-primary endpoint in the large part of comparative clinical trials about biologic anti-cancer agents. Here, we describe the “border time” bias represented by specific time points and intervals that are an underestimated source of methodologic heterogeneity and can contribute to wrong evaluation of time-to-outcome. These issues are concentrated at the beginning (head: pre-screening and screening activities) and at the end (tail: modalities of disease reassessment) of the anti-cancer treatment and can represent a time-related bias. Reporting, and ideally shortening, the time spent in pre-screening and screening activities with synthetic and innovative methodological tools as well as more harmonized rules about timing of disease reassessment can contribute to reduce, or even prevent, this bias in clinical studies.
Transposable Elements as a Source of Novel Repetitive DNA in the Eukaryote Genome
Authors: Zattera Michelle Louise , Bruschi Daniel Pacheco
Published: October 2022

The impact of transposable elements (TEs) on the evolution of the eukaryote genome has been observed in a number of biological processes, such as the recruitment of the host’s gene expression network or the rearrangement of genome structure. However, TEs may also provide a substrate for the emergence of novel repetitive elements, which contribute to the generation of new genomic components during the course of the evolutionary process. In this review, we examine published descriptions of TEs that give rise to tandem sequences in an attempt to comprehend the relationship between TEs and the emergence of de novo satellite DNA families in eukaryotic organisms. We evaluated the intragenomic behavior of the TEs, the role of their molecular structure, and the chromosomal distribution of the paralogous copies that generate arrays of repeats as a substrate for the emergence of new repetitive elements in the genome. We highlight the involvement and importance of TEs in the eukaryote genome and its remodeling processes.
Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease
Authors: Garcia Gonçalo , Pinto Sara , Ferreira Sofia , Lopes Daniela , Serrador Maria João , Fernandes Adelaide , Vaz Ana Rita , Mendonça Alexandre de , Edenhofer Frank , Malm Tarja , Koistinaho Jari , Brites Dora
Published: October 2022

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with neuron–glia dysfunction and dysregulated miRNAs. We previously reported upregulated miR-124/miR-21 in AD neurons and their exosomes. However, their glial distribution, phenotypic alterations and exosomal spread are scarcely documented. Here, we show glial cell activation and miR-21 overexpression in mouse organotypic hippocampal slices transplanted with SH-SY5Y cells expressing the human APP695 Swedish mutation. The upregulation of miR-21 only in the CSF from a small series of mild cognitive impairment (MCI) AD patients, but not in non-AD MCI individuals, supports its discriminatory potential. Microglia, neurons, and astrocytes differentiated from the same induced pluripotent stem cells from PSEN1ΔE9 AD patients all showed miR-21 elevation. In AD neurons, miR-124/miR-21 overexpression was recapitulated in their exosomes. In AD microglia, the upregulation of iNOS and miR-21/miR-146a supports their activation. AD astrocytes manifested a restrained inflammatory profile, with high miR-21 but low miR-155 and depleted exosomal miRNAs. Their immunostimulation with C1q + IL-1α + TNF-α induced morphological alterations and increased S100B, inflammatory transcripts, sAPPβ, cytokine release and exosomal miR-21. PPARα, a target of miR-21, was found to be repressed in all models, except in neurons, likely due to concomitant miR-125b elevation. The data from these AD models highlight miR-21 as a promising biomarker and a disease-modifying target to be further explored.
A New Model of Acute Exacerbation of Experimental Pulmonary Fibrosis in Mice
Authors: Yegen Céline-Hivda , Haine Liasmine , Da Costa Ferreira Kevin , Marchant Dominique , Bernaudin Jean-Francois , Planès Carole , Voituron Nicolas , Boncoeur Emilie
Published: October 2022

Rationale: idiopathic pulmonary fibrosis (IPF) is the most severe form of fibrosing interstitial lung disease, characterized by progressive respiratory failure leading to death. IPF’s natural history is heterogeneous, and its progression unpredictable. Most patients develop a progressive decline of respiratory function over years; some remain stable, but others present a fast-respiratory deterioration without identifiable cause, classified as acute exacerbation (AE). Objectives: to develop and characterize an experimental mice model of lung fibrosis AE, mimicking IPF-AE at the functional, histopathological, cellular and molecular levels. Methods: we established in C57BL/6 male mice a chronic pulmonary fibrosis using a repetitive low-dose bleomycin (BLM) intratracheal (IT) instillation regimen (four instillations of BLM every 2 weeks), followed by two IT instillations of a simple or double-dose BLM challenge to induce AE. Clinical follow-up and histological and molecular analyses were done for fibrotic and inflammatory lung remodeling analysis. Measurements and main results: as compared with a low-dose BLM regimen, this AE model induced a late burst of animal mortality, worsened lung fibrosis and remodeling, and superadded histopathological features as observed in humans IPF-AE. This was associated with stronger inflammation, increased macrophage infiltration of lung tissue and increased levels of pro-inflammatory cytokines in lung homogenates. Finally, it induced in the remodeled lung a diffuse expression of hypoxia-inducible factor 1α, a hallmark of tissular hypoxia response and a major player in the progression of IPF. Conclusion: this new model is a promising model of AE in chronic pulmonary fibrosis that could be relevant to mimic IPF-AE in preclinical trials.